TW201022666A - Methods and apparatus for analyzing samples and collecting sample fractions - Google Patents

Methods and apparatus for analyzing samples and collecting sample fractions Download PDF

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TW201022666A
TW201022666A TW098115071A TW98115071A TW201022666A TW 201022666 A TW201022666 A TW 201022666A TW 098115071 A TW098115071 A TW 098115071A TW 98115071 A TW98115071 A TW 98115071A TW 201022666 A TW201022666 A TW 201022666A
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Taiwan
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detector
fluid
sample
iii
shuttle valve
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TW098115071A
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Chinese (zh)
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James M Anderson Jr
Raaidah Saari-Nordhaus
Washington Mendoza
Josef P Bystron
Dirk Helgemo
Bruce D Black
Neil R Picha
Creary Dennis K Mc
Sheldon Nelson
Carl H Poppe
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Alltech Associates Inc
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Priority claimed from PCT/US2008/013359 external-priority patent/WO2009075764A2/en
Application filed by Alltech Associates Inc filed Critical Alltech Associates Inc
Publication of TW201022666A publication Critical patent/TW201022666A/en

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Abstract

Methods and apparatus for analyzing a sample using at least one detector are disclosed.

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201022666 六、發明說明: 【發明所屬之技術領域】 本發明係針對一種藉一層析系統來分析樣本及收集樣 本成分之方法及設備。 【先前技術】 在本技藝中需要一種藉一層析系統來有效率且具效地 分析樣本及收集樣本成分之方法。在本技藝中亦需要一種 能夠有效地分析樣本及收集樣本成分之設備。 【發明內容】 本發明有關於發現一種藉一層析系統分析樣本及收集 樣本成分之方法。所揭示之方法提供數個優於已知分析樣 ·. 本方法之優點。例如,所揭示之本發明方法可運用一分流 ' 泵或一梭閥來主動地控制通過至少一偵檢器之流體,使得 處理變數(譬如,流動阻力、總流率、溫度、及/或溶劑組 成物)不致對通過該至少一偵檢器之流體產生負面衝擊。所 〇 揭示之本發明方法亦可運用二個或更多偵檢器來對一給定 樣本提供一更完整之分析,以及反應來自該二個或更多偵 檢器之一個或更多偵檢器信號,收集一個或更多樣本成分。 本發明係針對一種分析樣本及收集樣本成分之方法。 在某一例示性實施例中,該分析一樣本之方法的步驟包 括:由一液相層析系統中之二個或更多偵檢器生成一組合 信號,該組合信號包括來自每一偵檢器之一偵檢反應組成 部;及反應該組合信號中之一變化,將一新樣本成分收集 201022666 於一成分收集器中。在某一實施例中,該組合信號可包括 (i)來自至少一光學吸光偵檢器(譬如,一紫外線(UV)偵檢器) 之一偵檢反應組成部,及(ii)來自至少一蒸發微粒偵檢器之 一偵檢反應組成部。在某一實施例中,可在該層析系統中 運用載色或非載色溶劑,作爲載運流體。在另一實施例中, 該組合信號可包括(i) 一偵檢反應組成部,其包括來自一光 學吸光偵檢器(譬如,一紫外線偵檢器)在二個或更多特定 光學波長下之二個或更多偵檢器反應,及(ii)來自一蒸發微 ❹ 粒偵檢器之一偵檢反應組成部。 在依據本發明之又一例示性實施例中,該使用層析法 分析一樣本之方法的步驟包括:使用至少一偵檢器觀察包 括有至少一非載色待測化合物之該樣本;及反應一偵檢器 反應中關於該非載色化合物之一變化,將一新樣本成分收 集於一成分收集器中。該樣本可包含眾多不同的載色與非 載色化合物。另,運送該樣本之移動相可包含一個或更多 ❹ 載色或非載色化合物。 在另一實施例中,可在該層析系統中運用通用之載運 流體,其包含揮發性液體及各種氣體。在又一實施例中, 一非破壞性偵檢器(譬如,折射率(RI)、紫外線偵檢器等) 可與一破壞性偵檢器(譬如,蒸發微粒偵檢器、質譜儀、光 譜儀、發射光譜法、核磁共振(NMR)等)相結合,該破壞性 者可允許偵檢該樣本之各種化合物特定特性,如關聯於峰 値之化學個體(entity)。 201022666 在又一例示性實施例中’該分析一樣本之方法的步驟 包括:使用至少一偵檢器’而在二個或更多特定波長下觀 察一樣本;及反應(i) 一第一偵檢器反應在一第一波長下 之一變化,(ii) 一第二偵檢器反應在一第二波長下之一變 化,或(iii)該等偵檢器反應所表達之一組合反應在該等第 一與第二波長下的一變化’將一新樣本成分收集於一成分 收集器中。一給定偵檢器反應中之一變化可包含、但不限 於一偵檢器反應値中之一變化、到達或超過一臨界偵檢器 反應値、該偵檢器反應値經歷一段時間之一斜率、該偵檢 器反應値經歷一段時間之一臨界斜率、該偵檢器反應値之 一斜率經歷一段時間的一變化、該偵檢器反應値之一斜率 經歷一段時間的一臨界變化、或其任何組合。在本實施例 中,該方法可包括:使用至少一偵檢器中之η個感測器, 觀察橫跨一吸光頻譜之一範圍內的η個特定波長,其中η 係大於1之一整數;及反應(i)來自該η個感測器之η個 φ 偵檢器反應中任一個的一變化,或(ii)由該η個偵檢器反應 所表達之一組合反應中的一變化,將一新樣本成分收集於 該成分收集器中。 在更又一例示性實施例中,該分析一樣本之方法的步 驟包括:提供一液相層析系統,其包括(i)—層析管柱,(ii) —三通閥,具有一第一進口,一第一出口,及一第二出口, (iii) 一成分收集器,與該三通閥之該第一出口以流體連 通,及(iv)—偵檢器,與該三通閥之該第二出口以流體連 201022666 通;及經由定位成與該三通閥之該第二出口及該偵檢器以 流體連通之(V)—分流泵’主動地控制通過該偵檢器之流 體。在其他例示性實施例中,可使用一梭閥取代該三通閥 及分流泵,主動地控制通過至少一偵檢器之流體。在一例 示性實施例中,該梭閥係一連續流梭閥,其具有自樣本流 束移開極小樣本體之能力。 在本發明之又更一例示性實施例中,一種使用層析法 Φ 分析一流體樣本之方法的步驟包含:提供自一層析管柱流 出之一第一流體;提供一第二流體,將該流體樣本運送到 至少一偵檢器;使用一梭閥,自該第一流體移開一整分流 體樣本,及將該整分轉運至該第二流體且同時維持該第二 流體通過該梭閥之一連續路徑;使用至少一偵檢器來觀察 該流體整分樣本;及反應一偵檢器反應中之一變化,將該 第一流體之一新樣本成分收集於一成分收集器中。在某一 實施例中,當自該第一流體移開該流體整分樣本時,該第 ® —流體通過該梭閥之一連續流動路徑仍將維持。在另一實 施例中,當該流體整分樣本自該第一流體移開且轉運至該 第二流體時,該第一流體及該第二流體二者通過該梭閥之 連續流動路徑,仍將維持。 在依據本發明之另一例示性實施例中,一種使用層析 法分析一流體樣本之方法的步驟包含:提供包括有該樣本 之一第一流體;使用一梭閥以自該第一流體移開一整分流 體樣本,而大致不影響通過該梭閥之該第一流體的流動特 201022666 性;使用至少一偵檢器來觀察該整分流體樣本 至少一偵檢器樣本之一變化,將該第一流束之 分收集於一成分收集器中。基於該第一流體路 大致線性或筆直地通過該閥之至少一部分,通 該第一流體流動可大致呈層流。在又一例示性 通過該梭閥之該第一流體壓力係大致保持定値 致不增加。在另一實施例中,通過該梭閥之該 率可大致呈定値。在一替代實施例中,可運用一 將該整分流體樣本自該梭閥運送至該(等)偵檢 第二流體路徑或通道係大致線性或筆直地通過 一部分,通過該梭閥之該第二流體流動可大致 一例示性實施例中,通過該梭閥之該第二流體 定値,及/或其大致不增加。在另一實施例中, 之該第二流體流率可大致呈定値。 在又一例示性實施例中,該分析一樣本之 φ 供一非破壞性系統液相層析系統之步驟,該系 層析管柱,(ii)二個或更多非破壞性偵檢器(譬 外線偵檢器等一光學吸光偵檢器),且該系統中 破壞性偵檢器(譬如,一質譜儀),及(iii)一成分 該二個或更多非破壞性偵檢器以流體連通;及 二個或更多非破壞性偵檢器之偵檢器信號,收 多樣本成分》 在依據本發明之另一例示性實施例中,一 :及反應該 一新樣本成 徑或通道係 過該梭閥之 實施例中, ,及/或其大 第一流體流 •第二流體, 器。基於該 該閥之至少 呈層流。在 壓力係大致 通過該梭閥 方法包括提 統包括(i) — 如,如一紫 不存有任何 收集器,與 反應來自該 集一個或更 種使用快速 201022666 層析法分析一流體樣本之方法的步驟包含:使用能夠偵檢 出各別化合物之一蒸發微粒偵檢器,觀察該樣本;及反應 關於該化合物之一偵檢器反應中的一變化,將一新樣本成 分收集於一成分收集器中,其中該蒸發微粒偵檢器係唯一 用於分析該樣本之偵檢器。該蒸發微粒偵檢器能夠偵檢化 學成分、化學結構、分子重量、或著其他化學或物理特性。 該偵檢器可包含一蒸發光散射偵檢器(ELSD)、凝聚成核光 散射偵檢器(CNLSD)、或質譜儀。 在更又一例示性實施例中,該分析一樣本之方法的步 驟包括:由一液相層析系統中之至少一偵檢器生成一偵檢 器信號,該偵檢器信號之生成係反應 (i)一偵檢器反應以 時間爲函數之斜率(即,一偵檢器反應之一階導數),(ii)該 偵檢器反應以時間爲函數之斜率的一變化(即,該偵檢器反 應之二階導數),(iii)可任選地,到達或超過一臨界偵檢器 反應値,或(iv)該⑴至(iii)之任何組合,而符合期望地包括 φ 至少⑴或至少(ii);及反應來自該至少一偵檢器之至少一偵 檢器信號,收集一個或更多樣本成分。 在又另一例示性實施例中,該分析一樣本之方法的步 驟包括:將一樣本成分收集於一液相層析系統之一成分收 集器中,其中該成分收集器係作動式地調整成適應於(i)識 別、接收、及處理來自至少一偵檢器之一個或更多信號, 及(ii)根據該一個或更多信號爲基礎,收集一個或更多樣本 成分。 201022666 本發明亦針對一種能夠分析一樣本之設備。在某一例 示性實施例中,該分析一樣本之設備包括系統硬體,作動 式地調整成適應於,由一液相層析系統中之二個或更多偵 檢器生成一組合信號,該組合信號包括來自每一偵檢器之 一偵檢反應組成部;及一成分收集器,作動式地調整成適 應於,反應該組合信號中之一變化,收集一新樣本成分。 在又另一例示性實施例中,該分析一樣本之設備包括 至少一偵檢器,作動式地調整成適應於觀察二個或更多特 定光學波長(譬如,紫外線波長);及一成分收集器,反應(i) 一偵檢器反應在一第一波長下之一變化,(ii)一偵檢器反應 在一第二波長下之一變化,或(iii)該等偵檢器反應所表達 之一組合反應在該等第一與第二波長下的一變化’收集一 新樣本成分。如上所述者,一給定偵檢器反應中之一變化 可包含、但不限於一偵檢器反應値中之一變化、到達或超 過一臨界偵檢器反應値、該偵檢器反應値經歷一段時間之 一斜率、該偵檢器反應値經歷一段時間之一臨界斜率、該 偵檢器反應値之一斜率經歷一段時間的一變化、該偵檢器 反應値之一斜率經歷一段時間的一臨界變化、或其任何組 合。 該至少一偵檢器可總共包括η個感測器,觀察橫跨一 吸光頻譜之一範圍內的η個特定波長’其中η係大於1之 一整數,及該成分收集器’作動式地調整成適應於,反應(i) 來自該η個感測器之η個偵檢器反應中任一個的一變化’ 201022666 或(ii)由該η個偵檢器反應所表達之一組合反應中的一變 化,收集一新樣本。在某一實施例中,該設備可包括一單 一紫外線偵檢器,其單獨包括了 η個感測器、或其可結合 一個或更多附加偵檢器。 在更又一例示性實施例中,該分析一樣本之設備包括 系統硬體,其允許由一個或更多偵檢器反應生成一偵檢器 信號。在某一例示性實施例中,該設備包括系統硬體,其 允許由一液相層析系統中之至少一偵檢器生成一偵檢器信 ❹ 號,該偵檢器信號之生成係反應(i)一偵檢器反應以時間 爲函數之斜率(即,一偵檢器反應之一階導數),(ii)該偵檢 器反應斜率以時間爲函數之一變化(即,該偵檢器反應之二 階導數),(iii)可任選地,到達或超過一臨界偵檢器反應値, 或(iv)該⑴至(iii)之任何組合,而符合期望地包括至少⑴ 或至少(ii)。該設備可尙包括一成分收集器,作動式地調整 成適應於,反應來自該至少一偵檢器之該偵檢器信號,收 φ 集一個或更多樣本成分。 在依據本發明之另一例示性實施例中,一種使用層析 法分析一流體樣本之設備包含至少一偵檢器,其能夠偵檢 出該樣本中之載色與非載色待測化合物;及一成分收集 器’其能夠反應一偵檢器反應中關於該非載色化合物之一 變化。該樣本可包含眾多不同的載色與非載色化合物。另, 運送該樣本之移動相可包含一個或更多載色或非載色化合 物。 -10 - 201022666 在更又一例示性實施例中,該分析一樣本之設備包括 (i) 一層析管柱;(ii) —三通閥,具有一第一進口,一第一出 口’及一第二出口;(iii) 一成分收集器,與該三通閥之該 第一出口以流體連通;(iv)—第一偵檢器,與該三通閥之該 第二出口以流體連通;及(v) —分流泵,定位成與該三通閥 之該第二出口及該第一偵檢器以流體連通,該分流泵係作 動式地調整成適應於,主動地控制通過該第一偵檢器之流 體。在其他例示性實施例中,可使用一梭閥取代該三通閥 0 及分流泵,來主動地控制通過至少一偵檢器之流體。在一 例示性實施例中,該梭閥係一連續流梭閥。 在依據本發明之又更一實施例中,一種使用層析法分 析一流體樣本之設備包含一第一流體路徑,自一層析管柱 或卡匣流出;至少一偵檢器,能夠分析該流體樣本;及一 梭閥,可將一整分流體樣本自該第一流體路徑轉運至該(等) 偵檢器,而大致不影響通過該第一流體路徑之流體的流體 φ 特性。由於該第一流體路徑或通道係大致線性或筆直地通 過該閥之至少一部分,因此通過該第一流體路徑之流體流 動可大致呈層流。在又一例示性實施例中,通過該第一流 體路徑之流體壓力可大致保持定値、及/或其大致不增加。 在另一實施例中,該流體之流率在通過該第一流體路徑 時,可大致呈定値。在一替代實施例中,可運用一第二流 體路徑’以將該整分流體樣本自該梭閥運送至該(等)偵檢 器。由於該第一流體路徑或通道係呈大致線性或筆直地通 -11- 201022666 過該閥之至少一部分,因此通過該第二流體路徑之流體流 動可大致呈層流。在一例示性實施例中,通過該第二流體 路徑之流體壓力可大致爲定値、及/或其大致不增加。在又 一實施例中,該流體之流率在通過該第二流體路徑時,可 大致呈定値。 在又更一例示性實施例中,一種使用層析法分析一流 體樣本之設備包含一第一流體路徑,自一層析管柱或卡匣 流出;一第二流體路徑,將該流體樣本運送至能夠分析該 ❹ 流體樣本之至少一偵檢器;及一梭閥,可將一整分流體樣 本自該第一流體路徑轉運至該第二流體路徑,且同時維持 住貫通該梭閥之一連續第二流體路徑。在某一實施例中, 當該整分流體樣本自該第一流體路徑移開時,仍可維持住 貫通該梭閥之一連續第一流體路徑。在另一實施例中,當 該整分流體樣本自該第一流體路徑移開且轉運至該第二流 體路徑時,仍可維持住貫通該梭閥之連續第一及第二流體 Φ 路徑。 在又一例示性實施例中,該分析一樣本之設備包括(i) 層析管柱;(ii)二個或更多非破壞性偵檢器,且該系統內無 任何破壞性偵檢器;(iii)一成分收集器,與該二個或更多 非破壞性偵檢器以流體連通,該成分收集器係作動式地調 整成適應於,反應來自該二個或更多非破壞性偵檢器之一 個或更多偵檢器信號,收集~個或更多樣本成分。 在依據本發明之又更一實施例中,一種使用快速層析 -12- 201022666 法分析一流體樣本之設備包含一蒸發微粒偵檢器’其能夠 偵檢出該樣本中之各別化合物;及一成分收集器’其能夠 反應關於該偵檢出之化合物的一偵檢器反應中之一變化’ 其中該蒸發微粒偵檢器係唯一用於分析該樣本之偵檢器。 該蒸發微粒偵檢器能夠偵檢化學成分、化學結構、分子重 量、或著其他物理或化學特性。該偵檢器可包含一蒸發光 散射偵檢器ELSD、凝聚成核光散射偵檢器CNLSD、或質譜 儀。 在又另一例示性實施例中,該分析一樣本之設備包括 一液相層析系統中之一成分收集器,該成分收集器係作動 式地調整成適應於(i)識別、接收、及處理來自至少一偵檢 器之一個或更多信號,及(ii)根據該一個或更多信號爲基 礎,收集一個或更多樣本成分。 本發明之方法及設備可包括至少一偵檢器。適合之偵 檢器包含、但不限於非破壞性偵檢器(即,偵檢期間不消耗 或破壞樣本之偵檢器),如紫外線UV、折射率RI、導電性、 螢光、光散射、黏度測定法、旋光測定法、及相似者;及/ 或破壞性偵檢器(即,偵檢期間消耗或破壞樣本之偵檢器) (EPD),如,譬如爲蒸發光散射偵檢器(ELSD)、凝聚成核光 散射偵檢器(CNLSD)等之蒸發微粒偵檢器(EPD),電暈放 電、質譜測定法、原子吸收、及相似者。例如,本發明之 設備可包含至少一紫外線(UV)偵檢器、至少一蒸發光散射 偵檢器(ELSD)、至少一質譜儀(MS)、至少一凝聚成核光散 -13- 201022666 射偵檢器(CNLSD)、至少一電暈放電偵檢器(CDD)、至少一 折射率偵檢器(RID)、至少一螢光偵檢器(FD)、至少一手性 偵檢器(CD)、或其任何組合。在某一例示性實施例中,該 偵檢器可包括一個或更多蒸發微粒偵檢器(EPD),其容許使 用載色及非載色溶劑作爲該移動相。在又一實施例中,一 非破壞性偵檢器可結合一破壞性偵檢器,其允許偵檢樣本 之各種化合物特定特性、分子重量、化學結構、基本成分、 及樣本手性,譬如關聯於峰値之化學個體等。 ❹ 本發明又更針對電腦可讀式媒體,其上儲存有電腦可 執行之指令’用於實施此中所描述之任何例示性方法中的 一個或更多方法步驟。該電腦可讀式媒體可用於將應用程 式碼載入至一設備、或譬如此中所描述之任何設備組件等 一設備組件中,以(i)提供一操作者介面,及/或(ii)提供可 用於實施此中所描述之一個或更多方法步驟的邏輯操作。 本發明之這些及其他特點,將在檢視以下揭示之實施 φ 例詳細說明、及附屬申請專利範圍後,而趨於明顯。 【實施方式】 爲了促進對本發明原理的了解,接著,進行本發明特 定實施例之說明,且使用特定用語於描述該等特定實施 例。然請了解到’特定用語之使用,並非意欲對本發明之 範疇加諸任何限制。針對此中討論之本發明原理,可預期 到其變更、進一步修飾、及如此般之進—步應用,如熟知 本發明所屬技藝之人士通常可發現者。 -14- 201022666 請務必注意到,如此中及附屬申請專利範圍所使用 者,除非文中另有清楚指明,否則單數型之「一」及「該」 包含複數個指示物。是以,例如提及「一溶劑」者,包含 複數個此種溶劑,且提及「溶劑」者,包含提及一個或更 多溶劑、及熟知此項技藝之人士已知的其等.效物等。 描述本案實施例時,用於修飾譬如一組成物中組成成 分之數量、濃度、體積、處理溫度、處理時間、回收或產 率、流率、及類似數値、及其範圍的「大約」,係指可譬 如因典型量測與處置程序、因這些程序中不經意地出錯、 因實行該等方法用之組成要素差異及同樣的相近考慮,而 發生之數値量變動。「大約」一詞亦涵蓋因具有一特殊初 始濃度或混合物之一配方,隨時間老化而有所差異的總 量、及因混合或處理具有一特殊初始濃度或混合物之一配 方而有所差異的總量。無論是否以「大約」一詞修飾,附 屬於此之申請專利範圍皆包含這些數量之等效者。 在此所用「層析」一詞意指一物理分離方法,其中待 分離之組成物係分佈於二相之間,其一爲固定(固定相), 而另一個(移動相)則沿一限定方向運動。 在此所用「液相層析」一詞意指,藉由使溶解於一「移 動相」中之一流體混合物通過包括有一固定相之一管柱, 來達成之混合物分離,其可將待測物(即,目標物質)與該 混合物中之其他分子分離,且容許其隔離。 在此所用「移動相」一詞意指一流體液體、一氣體、 -15- 201022666 或一超臨界流體’其包括待分離及/或分析之樣本、及可移 動包括有待測物之樣本通過管柱的溶劑。移動相可移動通 過層析管柱、或卡匣(即,包覆固定相之容器),樣本中之 待測物將於該處,與固定相交互作用,且與該樣本分離。 在此所用「固定相」一詞意指,固定於管柱或卡匣中 之材料,其可選擇性地自移動相中之樣本哮收待測物,而 藉由使溶解於一「移動相」中之一流體混合物通過包括有 一固定相之一管柱,來達成混合物分離,可將待測量之待 Φ 測物與該混合物中之其他分子分離,且容許其隔離。 在此所用「快速層析」一詞意指,藉由使在壓力下溶 解於一「移動相」中之一流體混合物通過包括有一固定相 之一管柱,來達成之混合物分離,其可將待測物(即,目標 物質)與該混合物中之其他分子分離,且容許其隔離。 在此所用「梭閥」一詞意指一控制閥,其可調節自一 個或更多(複數)源至另一位置的流體供應。梭閥可運用旋 Φ 轉或線性運動,來將一樣本自某一流體運動至另一個。 在此所用「流體」一詞意指一氣體、液體、及超臨界 流體。 在此所用「層流」一詞意指一流體之平穩、規律地運 動,其中無任何擾流,且任何給定的潛流(subcurrent)將與 任何其他附近的潛流幾近平行地運動。 在此所用「大致」一詞意指在一合理總量內,但包含 由絕對數値變動大約〇%至大約50%、大約〇%至大約40%、 -16- 201022666 大約0%至大約30%、大約0%至大約20%、或大約0%至大 約10%的總量。 本發明係針對一種分析樣本及收集樣本成分之方法。 本發明又針對一種能夠分析樣本及收集樣本成分之設備。 本發明又更針對適合用於能夠分析樣本及收集樣本成分之 一設備或複數設備組件中的電腦軟體,其中該電腦軟體允 許該設備實施如此中所描述之一個或更多方法步驟。 # 以下將針對例示性的分析樣本方法、及能夠分析樣本 之設備作一說明。 I、分析樣本之方法 本發明係針對一種分析樣本及收集樣本成分之方法。 這種分析一樣本之方法可包含有若干製程步驟,其中某些 將於以下說明。 A、主動控制流動至一偵檢器之流體 在本發明之某些實施例中,分析一樣本之方法包括一 φ 步驟,其包括經由一分流泵或一梭閥主動地控制流動至一 偵檢器之流體。第1圖顯示出,描繪此一方法步驟之一例 示性液相層析系統。如第1圖中所顯示者,一例示性液相 層析系統10包括(i)—層析管柱n,(ii)一三通閥12,具有 —第一入口 21、一第一出口 22、及一第二出口 23,(iii) —成分收集器14,與三通閥12之第一出口 22以流體連通, (iv)—第一偵檢器13,與三通閥12之第二出口 23以流體 連通,及(v) —分流泵15,定位成可與三通閥12之第二出 -17- 201022666 口 23、及第一偵檢器13以流體連通。 在本例示性系統中,分流泵1 5可主動地控制流動至第 一偵檢器13之流體。此中使用者,「主動地控制」一詞係 指一給定分流泵或梭閥能夠控制通過一給定偵檢器之流體 的能力,即使流體流率在該液相層析系統之其他部分中有 所變化時亦然。不同於僅分流流體之「被動」流體分流器, 本發明中使用之分流器及梭閥係控制流動到至少一偵檢器 之流體,而不考慮該液相層析系統內之譬如流動阻力、總 流率、溫度、及/或溶劑組成物等流體的可能波動。 主動地控制流動至一給定偵檢器之流體的步驟可包 括,譬如傳送一致動信號至該分流泵或梭閥,來(i)致動該 分流泵或梭閥,(ii)解除致動該分流泵或梭閥,(iii)改變該 分流泵或梭閥之一個或更多流動及/或壓力設定,或(iv)該 (i)至(iii)之任何組合。適當之流動及壓力設定包含、但不 限於(i) 一閥位置,(ii)分流泵或梭閥壓力,(iii)提供至一閥 0 之氣壓,或(iv)該⑴至(iii)之任何組合。典型地,該致動信 號係呈譬如一電氣信號、一氣動信號、一數位信號、或一 無線信號。 如第1圖中所顯示者,在例示性液相層析系統1 0中, 主動地控制流動至偵檢器13之流體的步驟包括,使用分流 泵15,將流體自三通閥12抽吸至偵檢器13中。在其他實 施例中,主動地控制流動至一偵檢器之流體的步驟可包 括,使用一分流泵,將流體拉拖通過一偵檢器。這種系統 -18- 201022666 架構顯示於第2圖中。 第2圖描繪出一例示性液相層析系統20,其包括層析 管柱11;三通閥12,具有一第一入口 21,一第一出口 22, 及第二出口 23;成分收集器14,與三通閥12之第一出口 22以流體連通;第一偵檢器13,與三通閥12之第二出口 23以流體連通;及分流栗15,定位成可自三通閥12之第 二出口 23推動流體通過偵檢器13。 在某些期望之實施例中,譬如第3A圖至第3C圖中顯 ❹ 示之例示性梭閥151等一梭閥,係用於主動地控制流動至 譬如一偵檢器131等一偵檢器的流體。如第3A圖中所顯示 者,一例示性液相層析系統30包括層析管柱11; 一梭閥 151,具有一層析卡匣入口 111,一成分收集器出口 114, 一氣體或液體入口 115、及一偵檢器出口 113;成分收集器 14,與梭閥151之成分收集器出口 114以流體連通;一第 一偵檢器131,與梭閥151之偵檢器出口 113以流體連通; φ 及一流體供應裝置152,提供流體至梭閥151之氣體或液體 入口 1 15。 在本發明之又更一例示性實施例中,一種使用層析法 分析一流體樣本之方法的步驟包括,提供自一層析管柱流 出之一第一流體;提供一第二流體,將該流體樣本運送到 至少一偵檢器;使用一梭閥,自該第一流體移開一整分流 體樣本,及將該整分轉運至該第二流體且同時維持該第二 流體通過該梭閥之一連續路徑;使用至少一偵檢器來觀察 -19- 201022666 該流體整分樣本;及反應一偵檢器反應中之一變化’將該 第一流體之一新樣本成分收集於一成分收集器中。在某一 實施例中,當自該第一流體移開該流體整分樣本時,該第 一流體通過該梭閥之一連續流動路徑仍將維持。在另一實 施例中,當該流體整分樣本自該第一流體移開且轉運至該 第二流體時,該第一流體及該第二流體二者通過該梭閥之 連續流動路徑,仍將維持。 I 在依據本發明之另一例示性實施例中,一種使用層析 ❹ 法分析一流體樣本之方法的步驟包含,提供包括有該樣本 之一第一流體;使用一梭閥來自該第一流體移開一整分流 體樣本,而大致不影響通過該梭閥之該第一流體的流動特 性;使用至少一偵檢器來觀察該整分流體樣本;及反應該 至少一偵檢器樣本之一變化,將該第一流束之一新樣本成 分收集於一成分收集器中。基於該第一流體路徑或通道係 大致線性或筆直地通過該閥之至少一部分,該第一流體通 〇 過該梭閥之流動可大致呈層流。在又一例示性實施例中, 該第一流體通過該梭閥之壓力係大致保持定値,及/或其大 致不增加。在另一實施例中,該第一流體通過該梭閥之流 率可大致呈定値。在一替代實施例中,可運用一第二流體, 將該整分流體樣本自該梭閥運送至該(等)偵檢器。基於該 第二流體路徑或通道係大致線性或筆直地通過該閥之至少 一部分’該第二流體通過該梭閥之流動可大致呈層流。在 一例示性實施例中,該第二流體通過該梭閥之壓力係大致 -20- 201022666 呈定値,及/或其大致不增加。在另一實施例中,該第二流 體通過該梭閥之流率可大致呈定値。 第3B圖及第3C圖描繪出某一例示性實施例中之一梭 閥,如何在一給定液相層析系統內作動。如第3B圖中所顯 示者,梭閥151包括層析卡匣入口 111,其可自一層析管柱 (譬如,管柱11)提供流體流動至梭閥151; —外來進入樣本 整分體116;成分收集器出口 114,其可自梭閥151提供流 體流動至一成分收集器(譬如,成分收集器14);氣體或液 φ 體入口 115,其可提供氣體(譬如,空氣、氮等)、或液體(譬 如,一酒精)流動通過梭閥151之一部分;一排出樣本整分 體117;及偵檢器出口 113,其可自梭閥151提供流體流動 至一偵檢器(譬如,偵檢器131,例如一蒸發光散射偵檢器 (ELSD))。 當流體自層析卡匣入口 111通過梭閥151而流動至成 分收集器出口 114時,外來進入樣本整分體116將充滿一 φ 特定體積量流體,在此稱之爲樣本整分118(如第3B圖中之 陰影區顯示者)。在一期望之時間下,梭閥151可將外來進 入樣本整分體116內之樣本整分118轉運至排出樣本整分 體Π7內,如第3C圖中顯示者。一旦樣本整分118轉運至 排出樣本整分體117內,自入口 115流經排出樣本整分體 117之氣體或液體,即可將樣本整分118經由偵檢器出口 113傳輸至偵檢器13 1(譬如,一蒸發光散射偵檢器)。 可對梭閥151以程式規劃,以將一樣本整分(譬如,樣 -21- 201022666 本整分118)自一樣本移開,而在一期望之取樣頻率下傳輸 到至少一偵檢器。在某一例示性實施例中,該取樣頻率係 每10秒(s)至少1樣本整分(或每5秒至少1樣本整分、或 每3秒至少1樣本整分、或每2秒至少1樣本整分、或每 0.5秒至少1樣本整分、或每0.1秒至少1樣本整分)。 第10A圖至第10C圖描繪出本發明之一例示性梭閥, 及其如何於一給定液相層析系統內作動。如第1 0 A圖中所 顯示者,梭閥151包括層析卡匣入口 111,其可自一層析管 參 柱(譬如,管柱11)提供流體流動至梭閥151;通道117,連 接入口 111至出口 114;外來進入樣本整分體118,位在一 動態本體119之凹坑116中;成分收集器出口 114,其可自 梭閥151提供流體流動至一成分收集器(譬如,成分收集器 14);氣體或液體入口 115,其可提供氣體(譬如,空氣、氮)、 或液體(譬如,一酒精)通過梭閥151;排出樣本整分體118, 位在凹坑116中;一通道120,連接入口 115至出口 113; φ 及偵檢器出口 113,其可自梭閥151提供流體流動至一偵檢 器(譬如,偵檢器1 3 1,例如一蒸發光散射偵檢器)。 當流體經由通道117自層析卡匣入口 111通過梭閥151 而流動至成分收集器出口 114時,凹坑116中之外來進入 樣本整分體118將充滿一特定體積量流體,在此稱之爲樣 本整分1 18(如第10A圖中之陰影區顯示者)。在一期望之時 間下,梭閥151可藉由旋轉動態本體119中之凹坑116,而 經由一凹坑旋轉路徑121,將取自通道117之凹坑116內樣 -22- 201022666 本整分118轉運至通道120。一旦樣本整分118轉運至通道 120中’自入口 115流經通道120之氣體或液體,即可將樣 本整分118經由偵檢器出口 113傳輸至偵檢器131(譬如, 一蒸發光散射偵檢器)。本發明梭閥之另一優點係關於通過 該閥之通道的射流設計。爲了使該層析系統中之背壓最小 化’通過通道117及120之流動係呈連續。這可藉由將通 道117及120定位於一靜態本體.122中,使得不論動態本 體119位於何位置,通過梭閥151之流動皆呈連續(如第10B 圖中所顯示者)來實現。如自10A圖所顯示者,至少一部分 樣本流束通道117及偵檢器流束通道120可大致呈平面或 圓周型,如此可減少擾流、且進一步使通過該閥之壓力增 加最小化。此外,至少一部分樣本流束通道1 1 7及偵檢器 流束通道120,可在其與凹坑116連貫時,與該凹坑大致平 行,如此可更進一步限制擾流、及該閥中之任何壓力增加。 這包含不致使該閥內壓力增加超過 50英磅/平方英寸 φ (psi)、較佳地不超過30psi、更佳地不超過20psi、且甚佳 地不超過10、9、8、7、6、5、4、3、2、或lpsi之架構。 凹坑116係位於動態本體119中,且與鄰接著靜態本體122 之該動態本體面以流體連通,藉此當動態本體119位在一 第一位置時,凹坑116將與樣本流束通道Π7以流體連通, 且當運動至一第二位置時,凹坑116將與偵檢器流束通道 120以流體連通。凹坑116可爲任何外形,但將其描繪爲— 凹面半球形,且其可爲任何尺寸。在一例示性實施例中’ -23- 201022666 該凹坑之尺寸可極小(譬如,小於2000毫微升(nL)、較佳地 小於大約500nL、更佳地小於大約100nL、且甚至小於大約 InL,但可包含容許快速取樣之InL至2000nL的任何尺 寸)。另,小凹坑116尺寸容許一非常短之凹坑旋轉路徑 121,如此可大幅減少在動態本體119及靜態本體122表面 上的磨耗,且致使一梭閥151在需維修前,具有較爲延長 之服務壽命(譬如,可能在檢修前超過1千萬次運轉週期)。 僅管第10A圖至第10C圖中描繪出一旋轉運動梭閥,然線 性運動梭閥、或其等效者,皆可運用於本發明中。 可對梭閥151程式規劃,以自一樣本移開一樣本整分 (譬如,樣本整分118),而在一期望之取樣頻率下傳輸到至 少一偵檢器。在某一例示性實施例中,該取樣頻率係每1 0 秒至少1樣本整分(或每5秒至少1樣本整分、或每3秒至 少1樣本整分、或每2秒至少1樣本整分、或每0.5秒至 少1樣本整分、或每0.1秒至少1樣本整分)。該梭閥係於 共同申請之美國臨時專利申請案第_號中進一步說明, 其其全部內容已藉參考方式倂入本案中。 在另一實施例中,該層析系統中可運用包含揮發性液 體及各種氣體之通用載運流體,將一樣本運送至一偵檢 器。如第3A圖中所顯示者,來自流體供應裝置152之載運 流體,將於其拾取樣本整分118 (顯示於第10A圖中)之入口 115處,進入梭閥151中,且接著經由出口 113繼續前進至 偵檢器131。該樣本整分不應沉澱於該閥之載運流體中、或 -24- 201022666 使相關聯之配管開始變得堵塞、或著使該樣本塗覆於流動 路徑之壁、且某些或全部的樣本無法抵達該偵檢器。快速 層析中之樣本組成物可非常多樣化,而涵蓋了包含無機分 子、有機分子、聚合物、縮氨酸、蛋白質、及寡核酸等之 一廣範圍之化學化合物。不論同類別化合物內、及不同化 合物之間,在各種溶劑中之溶解度皆不同。偵檢器之相容 性亦侷限了可使用的載運流體型態。例如,對於紫外線(UV) 偵檢,溶劑在偵檢波長下應不載色。對於蒸發微粒偵檢(EPD) ❿ 技術(蒸發光散射偵檢器、凝聚成核光散射偵檢器、質譜儀 等),溶劑應可在相當程度地低於樣本熔點之一溫度下,輕 易地蒸發。另,載運流體應可與流動於閥入口 111與成分 收集器出口 114之間的樣本溶混。例如,倘某一流動路徑 中使用了己烷,則因己烷與水無法溶混,以致另一流動路 徑中不可使用水。以上者皆建議,載運流體應在每次分離 溶劑有所變化時,客制化訂製。如此將耗時且不切實際。 # 依據本發明之一例示性實施例,使用可與有機溶劑及水溶 混、具揮發性、且非載色的溶劑,將可避免此問題。例如, 譬如異丙醇(IPA)等一揮發性、非載色中極性溶劑,可用作 爲載運流體。IPA可與幾乎所有溶劑溶混、在一般紫外線 偵檢波長下不載色、且在低溫下輕易蒸發。另,IPA可溶 解一廣泛之化學品及化學類別。是以,IPA對於差不多所 有樣本型態,皆爲一適當載運流體。其他載運流體可包含 丙酮、甲醇、乙醇、丙醇、丁醇、異丁醇、四氫呋喃、及 -25- 201022666 相似者。在一替代例示性實施例中,可運用一氣體作爲載 運流體。由於該樣本在通過該梭閥、及隨後通過該偵檢器 時,仍保持於分離溶劑中、或呈移動相,因此不致遇到樣 本沉澱。相同地,該分離溶劑、或移動相決不與另一溶劑 混合,因此可溶混性並非一爭議問題。由於該載運者爲一 氣體,因此揮發性不再爲一爭議問題。另,大多數氣體不 載色,且與紫外線偵檢相容。當使用氣體作爲載運者時, 樣本整分118係自閥151流放至偵檢器131,而離散的小塊 物將夾擠於複數個氣囊123之間,如第10C圖所顯示者。 使用氣體作爲載運者具有其他優點。例如,當結合了樣本 需霧化之一蒸發光散射偵檢器或其他偵檢技術使用時,該 氣體可用於傳輸該樣本及霧化該樣本,而免除對一分離霧 化氣體供應裝置之需求。另,由於氣體不需蒸發,因此可 使用周邊漂移管溫度,而免除對漂移管加熱器之需求。由 於可在較高溫度下蒸發之樣本,現在將在其通過漂移管時 g 保持於固或液態,因此可偵檢一較廣泛之樣本。可使用包 含空氣、氮、氦、及二氧化碳等之各式各類氣體,作爲載 運氣體。亦可使用譬如超臨界二氧化碳等超臨界流體。 B、偵檢一捭體流束內之一樣本組成物 本發明之方法尙包括,使用至少一偵檢器來偵檢一流 體流束內之一個或更多組成物。適合用於本發明液相層析 系統中之偵檢器包含、但不限於非破壞性、及/或破壞性偵 檢器。適合之偵檢器包含、但不限於非破壞性偵檢器(即, -26- 201022666 偵檢期間不消耗或破壞樣本之偵檢器),如紫外線、折射 率、導電性、螢光、光散射、黏度測定法、旋光測定法、 及相似者;及/或破壞性偵檢器(即,偵檢期間消耗或破壞 樣本之偵檢器),如,譬如爲蒸發光散射偵檢器(ELSD)、一 凝聚成核光散射偵檢器(CNLSD)等之蒸發微粒偵檢器 (EPD),電暈放電、質譜測定法、原子吸收、及相似者。例 如,本發明之設備可包含至少一紫外線偵檢器、至少一蒸 發光散射偵檢器(ELSD)、至少一質譜儀(MS)、至少一凝聚 ® 成核光散射偵檢器(CNLSD)、至少一電暈放電偵檢器 (CDD)、至少一折射率偵檢器(RID)、至少一螢光偵檢器 (FD)、至少一手性偵檢器(CD)、或其任何組合。在一例示 性實施例中,偵檢器可包括一個或更多蒸發微粒偵檢器 (EPD),其容許使用載色與非載色溶劑作爲移動相。在又一 實施例中,一非破壞性偵檢器可與允許偵檢譬如化學個體 (entity)、化學結構、分子量等,關聯於每一載色峰値之樣 @ 本中各種化合物特定特性的一破壞性偵檢器相結合。當結 合質譜儀偵檢時,可在偵檢時決定成分之化學結構、及/或 分子量,而使對於需求成分之鑑別較具效率。在現有系統 中,必須藉麻煩的後分離技術,來決定成分之化學特徵及 結構。 無論所使用之偵檢器型態爲何,一給定偵檢器皆提供 一個或更多偵檢器反應,該等反應可用於生成及傳送一信 號至一液相層析系統內的一個或更多組件(譬如,一成分收 -27- 201022666 集器、另一偵檢器、一分流泵、一梭閥、或一三通閥),如 此中所描述者。典型地,一給定偵檢器反應中之一變化可 觸發一信號之生成及傳送。在本發明中,可觸發生成及傳 送一信號至一個或更多組件之一給定偵檢器反應中的一變 化包含、但不限於一偵檢器反應値中之一變化、到達或超 過一臨界偵檢器反應値、該偵檢器反應値經歷一段時間之 一斜率、該偵檢器反應値經歷一段時間之一臨界斜率、該 偵檢器反應値之一斜率經歷一段時間的一變化、該偵檢器 @ 反應値之一斜率經歷一段時間的一臨界變化、或其任何組 合。 在某些例示性實施例中,本發明之液相層析系統包括 至少二偵檢器,如第4圖中所顯示者。第4圖中所顯示之 一例示性液相層析系統40包括層析管柱11;三通閥12, 具有第一入口 21、第一出口 22、及第二出口 23;成分收集 器14,與三通閥12第一出口 22以流體連通;第一偵檢器 @ 13,與三通閥12第二出口 23以流體連通;分流泵15,主 動地控制自三通閥12第二出口 23流動至第一偵檢器13之 流體;及一第二偵檢器16,與三通閥12第二出口 23以流 體連通。 當存有二個或更多偵檢器時,該液相層析系統提供一 操作者更多的分析選擇。例如,在第4圖中所顯示之例示 性液相層析系統40中,一種分析一樣本之方法可包括,自 第一偵檢器13(譬如,一蒸發光散射偵檢器)、及/或第二偵 -28- 201022666 檢器16(譬如,一光學吸光偵檢器,如一紫外線偵檢器)傳 送一個或更多信號至成分收集器14,以指示成分收集器14 收集一新樣本成分之一步驟。來自第一偵檢器13及/或第 二偵檢器16之該一個或更多信號可包括,來自第一偵檢器 13或第二偵檢器16之一單一信號、來自第一信號13及第 二信號16之二個或更多信號、或著來自第一偵檢器13及 第二偵檢器16之一組合信號。在第4圖中所顯示之例示性 液相層析系統40中,該分析一樣本之方法可尙包括自第二 響 偵檢器16傳送一信號至分流泵15之一步驟,以反應第二 偵檢器16偵檢到一流體流束中的一樣本組成物,來指示分 流栗15起始或停止流體流動至第一偵檢器13。 在其他例示性實施例中,本發明之液相層析系統包括 至少二偵檢器、及至少二分流泵,如第5圖中所顯示者。 第5圖中所顯示之一例示性液相層析系統50包括層析管柱 11;第一三通閥12,具有第一入口 21、第一出口 22、及第 • 二出口 23;第一偵檢器13,與第一三通閥12第二出口 23 以流體連通;第一分流泵15’主動地控制自第一三通閥12 第二出口 23流動至第一偵檢器13之流體;一第二三通閥 18,具有一第一入口 31、一第一出口 32、及一第二出口 33; 一第二偵檢器16’與第二三通閥18第二出口 33以流體連 通;一第二分流栗17,主動地控制自第二三通閥18第二出 口 33流至第二偵檢器16之流體;及成分收集器14,與第 二三通閥18第一出口 32以流體連通。 -29- 201022666 如上所述者,本發明之液相層析系統可包括位於適當 位置之一個或更多梭閥、或著一個或更多三通閥/分流泵組 合物,以主動地控制流體流動到至少一偵檢器,如第6圖 至第7圖中所舉例示範者。如第6圖中所顯示者,一例示 性液相層析系統60包括層析管柱11;梭閥151,具有層析 卡匣進口 111、成分收集器出口 114、氣體或液體進口 115、 及偵檢器出口 113;成分收集器14,與梭閥151之成分收 集器出口 114以流體連通;第一偵檢器131,與梭閥151 參 之偵檢器出口 113以流體連通;流體供應裝置152,提供流 體至梭閥151之氣體或液體進口 115;及一第二偵檢器 161,與梭閥151之偵檢器出口 113以流體連通。 如第7圖中所顯示者,一例示性液相層析系統70包括 層析管柱11;第一梭閥151,具有層析卡匣進口 111、成分 收集器出口 114、氣體或液體進口 115、及偵檢器出口 113; 第一偵檢器131,與梭閥151之偵檢器出口 113以流體連 φ 通;流體供應裝置152,提供流體至梭閥151之氣體或液體 進口 115; —第二梭閥171,具有一層析卡匣進口 121、一 成分收集器出口 124、一氣體或液體入口 125、及一偵檢器 出口 123;第二偵檢器161,與梭閥171之偵檢器出口 123 以流體連通;一流體供應裝置172,提供流體至梭閥171 之氣體或液體入口 125;及成分收集器14,與梭閥171之 成分收集器出口 124以流體連通。 在這些例示性實施例、亦即例示性液相層析系統50及 -30- 9201022666 VI. Description of the Invention: [Technical Field of the Invention] The present invention is directed to a method and apparatus for analyzing a sample and collecting sample components by a chromatography system. [Prior Art] There is a need in the art for a method of efficiently and efficiently analyzing a sample and collecting sample components by means of a chromatography system. There is also a need in the art for an apparatus that can efficiently analyze samples and collect sample components. SUMMARY OF THE INVENTION The present invention relates to the discovery of a method for analyzing a sample and collecting sample components by a chromatography system. The disclosed method provides several better than known samples.  The advantages of this method. For example, the disclosed method of the present invention can utilize a split 'pump or a shuttle valve to actively control fluid passing through at least one detector to process variables (eg, flow resistance, total flow rate, temperature, and/or solvent). The composition does not cause a negative impact on the fluid passing through the at least one detector. The disclosed method of the present invention may also utilize two or more detectors to provide a more complete analysis of a given sample, and to respond to one or more detections from the two or more detectors. Signal, collecting one or more sample components. The present invention is directed to a method of analyzing a sample and collecting sample components. In an exemplary embodiment, the analyzing of the method of the present method comprises: generating a combined signal from two or more detectors in a liquid chromatography system, the combined signal including from each detection One of the detectors detects the reaction component; and reacts to one of the combined signals to collect a new sample component in 201022666 in a component collector. In an embodiment, the combined signal may comprise (i) a detection reaction component from at least one optical absorption detector (for example, an ultraviolet (UV) detector), and (ii) from at least one One of the evaporative particle detectors detects the reaction component. In one embodiment, a carrier or non-coloring solvent can be employed in the chromatography system as the carrier fluid. In another embodiment, the combined signal can include (i) a detection reaction component comprising an optically absorptive detector (eg, an ultraviolet detector) at two or more specific optical wavelengths Two or more detectors react, and (ii) one of the detection reaction components from an evaporative microparticle detector. In still another exemplary embodiment of the present invention, the step of analyzing the same method using chromatography comprises: using at least one detector to observe the sample comprising at least one non-carrier color test compound; and reacting A detector component reacts to one of the non-chromophoric compounds and collects a new sample component in a component collector. The sample can contain a wide variety of different color and non-carrier compounds. Alternatively, the mobile phase carrying the sample may contain one or more 载 carrier or non-ferrous compounds. In another embodiment, a universal carrier fluid can be utilized in the chromatography system that contains volatile liquids and various gases. In yet another embodiment, a non-destructive detector (eg, refractive index (RI), ultraviolet detector, etc.) can be associated with a destructive detector (eg, evaporative particle detector, mass spectrometer, spectrometer) In combination with emission spectroscopy, nuclear magnetic resonance (NMR), etc., the destructive person may allow detection of specific properties of the various compounds of the sample, such as the chemical entity associated with the peak. 201022666 In yet another exemplary embodiment, the steps of the method of the present invention include: using at least one detector to observe the same at two or more specific wavelengths; and reacting (i) a first detect The detector reacts at one of the first wavelengths, (ii) a second detector reacts at one of the second wavelengths, or (iii) one of the detector responses is expressed in a combination A change in the first and second wavelengths 'collects a new sample component in a component collector. A change in a given detector response may include, but is not limited to, a change in one of the detector responses, a response to a critical detector, or a response to the detector. a slope, a critical slope of the detector response, a period of time, a slope of the detector response, a change in time, a slope of the detector response, a critical change over a period of time, or Any combination of them. In this embodiment, the method may include: using n sensors in the at least one detector to observe n specific wavelengths spanning one of a range of light absorption spectra, wherein η is greater than one integer of one; And reacting (i) a change from any of the n φ detector responses of the n sensors, or (ii) a change in a combined reaction expressed by the n detector responses, A new sample component is collected in the component collector. In still another exemplary embodiment, the method of the method of the present invention comprises: providing a liquid chromatography system comprising (i) a chromatography column, (ii) a three-way valve, having a first An inlet, a first outlet, and a second outlet, (iii) a component collector in fluid communication with the first outlet of the three-way valve, and (iv) a detector, and the three-way valve The second outlet is connected to the fluid connection 201022666; and actively controls the passage through the detector via a (V)-split pump positioned in fluid communication with the second outlet of the three-way valve and the detector fluid. In other exemplary embodiments, a shuttle valve may be used in place of the three-way valve and the splitter pump to actively control fluid passing through at least one detector. In an exemplary embodiment, the shuttle valve is a continuous flow shuttle valve having the ability to remove very small sample volumes from the sample stream. In still another exemplary embodiment of the present invention, a method of analyzing a fluid sample using chromatography Φ comprises: providing a first fluid flowing from a chromatography column; providing a second fluid, The fluid sample is transported to at least one detector; a shuttle valve is used to remove an entire fluid sample from the first fluid, and the whole is transferred to the second fluid while maintaining the second fluid through the shuttle a continuous path of the valve; using at least one detector to observe the fluid aliquot; and reacting one of the detector responses to collect a new sample component of the first fluid in a component collector. In one embodiment, when the fluid aliquot is removed from the first fluid, the continuous flow path of the first fluid through the shuttle valve will remain. In another embodiment, when the fluid aliquot is removed from the first fluid and transported to the second fluid, both the first fluid and the second fluid pass through the continuous flow path of the shuttle valve, Will be maintained. In accordance with another exemplary embodiment of the present invention, a method of analyzing a fluid sample using chromatography comprises: providing a first fluid comprising one of the samples; using a shuttle valve to move from the first fluid Opening a whole fluid sample without substantially affecting the flow of the first fluid through the shuttle valve; using at least one detector to observe a change in at least one of the detector samples of the entire fluid sample, The first stream is collected in a component collector. Based on the first fluid path passing substantially linearly or straightly through at least a portion of the valve, the first fluid flow can be substantially laminar. In still another exemplary embodiment, the first fluid pressure system through the shuttle valve remains substantially constant. In another embodiment, the rate through the shuttle valve can be substantially constant. In an alternate embodiment, the dispensing of the aliquot of the fluid sample from the shuttle valve to the (second) detection second fluid path or passageway is substantially linear or straight through a portion through which the shuttle valve is The two fluid flow can be substantially an exemplary embodiment in which the second fluid is fixed by the shuttle valve and/or it does not substantially increase. In another embodiment, the second fluid flow rate can be substantially constant. In yet another exemplary embodiment, the analysis is the same as the step of supplying a non-destructive system liquid chromatography system, the chromatography column, (ii) two or more non-destructive detectors (an optical light-detecting detector such as an external line detector), and a destructive detector (such as a mass spectrometer) in the system, and (iii) a component of the two or more non-destructive detectors In fluid communication; and two or more non-destructive detector detector signals, multi-sample components", in another exemplary embodiment in accordance with the present invention, one: and reacting to a new sample Or the passage is in the embodiment of the shuttle valve, and/or its large first fluid flow • second fluid. At least a laminar flow based on the valve. The pressure system generally passes through the shuttle valve method including extracting (i) - for example, if there is no collector present in a purple, and reacting one or more methods from the set using the rapid 201022666 chromatography method for analyzing a fluid sample The step comprises: observing the sample using an evaporative particle detector capable of detecting one of the individual compounds; and reacting a change in the reaction of the detector to one of the compounds, collecting a new sample component in a component collector Where the evaporative particle detector is the only detector used to analyze the sample. The evaporative particle detector is capable of detecting chemical composition, chemical structure, molecular weight, or other chemical or physical properties. The detector can include an Evaporative Light Scattering Detector (ELSD), a Condensed Nucleation Light Scattering Detector (CNLSD), or a mass spectrometer. In still another exemplary embodiment, the analyzing of the method of the present method comprises: generating a detector signal from at least one detector in a liquid chromatography system, the detector signal generating reaction (i) the slope of a detector response as a function of time (ie, the first derivative of a detector response), and (ii) a change in the slope of the detector response as a function of time (ie, the Detector) The second derivative of the detector reaction), (iii) optionally, reaching or exceeding a critical detector reaction, or (iv) any combination of (1) to (iii), and desirably including φ at least (1) or At least (ii); and reacting at least one detector signal from the at least one detector to collect one or more sample components. In yet another exemplary embodiment, the method of the method of the present invention comprises the steps of: collecting the same component in a component collector of a liquid chromatography system, wherein the component collector is operatively adjusted to Adapting to (i) identifying, receiving, and processing one or more signals from at least one detector, and (ii) collecting one or more sample components based on the one or more signals. 201022666 The present invention is also directed to an apparatus capable of analyzing the same. In an exemplary embodiment, the apparatus of the same analysis includes a system hardware that is operatively adapted to generate a combined signal from two or more detectors in a liquid chromatography system. The combined signal includes a detection reaction component from one of each detectors; and a component collector operatively adapted to respond to a change in one of the combined signals to collect a new sample component. In yet another exemplary embodiment, the apparatus of the same analysis includes at least one detector that is operatively adapted to view two or more specific optical wavelengths (eg, ultraviolet wavelengths); and a component collection , (i) a detector response that changes at one of the first wavelengths, (ii) a detector response that changes at a second wavelength, or (iii) the detector response A change in expression of one of the combinations at the first and second wavelengths 'collects a new sample component. As described above, a change in a given detector response may include, but is not limited to, a change in one of the detector responses, a threshold detector response, or a detector response. a slope that experiences a period of time, a critical slope of the detector response, a period of time, a slope of the detector response, a change in the period of time, and a slope of the detector response A critical change, or any combination thereof. The at least one detector may comprise a total of n sensors, observing n specific wavelengths in a range of one of the light absorption spectra, wherein the η is greater than one integer of 1 and the component collector is operatively adjusted Adapting to, reacting (i) a change from any of the n detector responses of the n sensors '201022666 or (ii) one of the combined reactions expressed by the n detector responses A change, collect a new sample. In one embodiment, the apparatus can include a single ultraviolet detector that individually includes n sensors, or it can incorporate one or more additional detectors. In still another exemplary embodiment, the apparatus of the same analysis includes system hardware that allows a detector signal to be generated by one or more detector responses. In an exemplary embodiment, the apparatus includes system hardware that allows a detector signal to be generated by at least one of the detectors in a liquid chromatography system, the detector signal generation reaction (i) a detector response is a function of the slope of time (ie, a detector derivative of the detector), (ii) the detector response slope changes as a function of time (ie, the detection The second derivative of the reaction, (iii) optionally, reaching or exceeding a critical detector reaction, or (iv) any combination of (1) to (iii), desirably including at least (1) or at least ( Ii). The apparatus can include a component collector operatively adapted to react to the detector signal from the at least one detector to collect one or more sample components. In another exemplary embodiment of the present invention, an apparatus for analyzing a fluid sample using chromatography comprises at least one detector capable of detecting a color-carrying and non-carrier-testing compound in the sample; And a component collector's capable of reacting to a detector reaction in response to one of the non-carrier compounds. The sample can contain a number of different color and non-carrier compounds. Alternatively, the mobile phase carrying the sample may comprise one or more color or non-carrier compounds. -10 - 201022666 In still another exemplary embodiment, the apparatus of the same analysis comprises (i) a chromatography column; (ii) a three-way valve having a first inlet, a first outlet' and a second outlet; (iii) a component collector in fluid communication with the first outlet of the three-way valve; (iv) a first detector in fluid communication with the second outlet of the three-way valve And (v) - a split pump positioned in fluid communication with the second outlet of the three-way valve and the first detector, the split pump being operatively adapted to actively control passage of the first A fluid of the detector. In other exemplary embodiments, a shuttle valve may be used in place of the three-way valve 0 and the splitter pump to actively control fluid flow through at least one detector. In an exemplary embodiment, the shuttle valve is a continuous flow shuttle valve. In still another embodiment of the present invention, an apparatus for analyzing a fluid sample using chromatography comprises a first fluid path flowing from a chromatography column or a cassette; at least one detector capable of analyzing the a fluid sample; and a shuttle valve for transporting an entire fluid sample from the first fluid path to the detector, without substantially affecting fluid φ characteristics of the fluid passing through the first fluid path. Since the first fluid path or passageway passes through at least a portion of the valve substantially linearly or straightly, fluid flow through the first fluid path can be substantially laminar. In yet another exemplary embodiment, the fluid pressure through the first fluid path may remain substantially constant, and/or it may not increase substantially. In another embodiment, the flow rate of the fluid can be substantially constant as it passes through the first fluid path. In an alternate embodiment, a second fluid path ' can be utilized to transport the aliquot of the fluid sample from the shuttle valve to the detector. Since the first fluid path or passageway is substantially linear or straight through at least a portion of the valve, fluid flow through the second fluid path can be substantially laminar. In an exemplary embodiment, the fluid pressure through the second fluid path may be substantially constant, and/or it may not increase substantially. In yet another embodiment, the flow rate of the fluid can be substantially constant as it passes through the second fluid path. In still another exemplary embodiment, an apparatus for analyzing a fluid sample using chromatography comprises a first fluid path flowing from a chromatography column or cassette; a second fluid path transporting the fluid sample And at least one detector capable of analyzing the sputum fluid sample; and a shuttle valve for transporting an entire fluid sample from the first fluid path to the second fluid path while maintaining one of the shuttle valves A continuous second fluid path. In one embodiment, a continuous first fluid path through one of the shuttle valves is maintained while the aliquot of the fluid sample is removed from the first fluid path. In another embodiment, the continuous first and second fluid Φ paths through the shuttle valve are maintained while the aliquot of the fluid sample is removed from the first fluid path and transported to the second fluid path. In yet another exemplary embodiment, the apparatus of the same analysis includes (i) a chromatography column; (ii) two or more non-destructive detectors, and there is no destructive detector within the system (iii) a component collector in fluid communication with the two or more non-destructive detectors, the component collector being operatively adapted to accommodate, the response from the two or more non-destructive One or more detector signals from the detector, collecting ~ or more sample components. In still another embodiment in accordance with the present invention, an apparatus for analyzing a fluid sample using the flash chromatography-12-201022666 method includes an evaporative particle detector that is capable of detecting individual compounds in the sample; A component collector 'which is capable of reacting to one of the detector responses to the detected compound' wherein the evaporative particle detector is the only detector used to analyze the sample. The evaporative particle detector is capable of detecting chemical composition, chemical structure, molecular weight, or other physical or chemical properties. The detector may include an evaporative light scattering detector ELSD, a condensed nucleation light scattering detector CNLSD, or a mass spectrometer. In yet another exemplary embodiment, the apparatus of the analysis includes a component collector in a liquid chromatography system that is operatively adapted to (i) identify, receive, and Processing one or more signals from at least one detector, and (ii) collecting one or more sample components based on the one or more signals. The method and apparatus of the present invention can include at least one detector. Suitable detectors include, but are not limited to, non-destructive detectors (ie, detectors that do not consume or destroy samples during detection), such as UV UV, refractive index RI, conductivity, fluorescence, light scattering, Viscosity measurement, optical rotation assay, and the like; and/or destructive detector (ie, a detector that consumes or destroys a sample during detection) (EPD), such as, for example, an evaporative light scattering detector ( ELSD), Evaporation Particle Detector (EPD) for condensed nucleation light scattering detector (CNLSD), corona discharge, mass spectrometry, atomic absorption, and the like. For example, the apparatus of the present invention may comprise at least one ultraviolet (UV) detector, at least one evaporative light scattering detector (ELSD), at least one mass spectrometer (MS), at least one condensed nucleate dispersion -13 - 201022666 Detector (CNLSD), at least one Corona Discharge Detector (CDD), at least one Refractive Index Detector (RID), at least one Fluorescence Detector (FD), at least one Chiral Detector (CD) , or any combination thereof. In an exemplary embodiment, the detector may include one or more evaporative particle detectors (EPDs) that permit the use of both color- and non-carrier solvents as the mobile phase. In yet another embodiment, a non-destructive detector can incorporate a destructive detector that allows detection of specific properties, molecular weights, chemical structures, basic components, and sample chirality of various compounds of the sample, such as associations. Yu Feng's chemical entity and so on. The present invention is further directed to a computer readable medium having stored thereon computer executable instructions' for implementing one or more of the method steps of any of the exemplary methods described herein. The computer readable medium can be used to load an application code into a device, or any device component such as any of the device components described herein, to (i) provide an operator interface, and/or (ii) Provides logical operations that can be used to implement one or more of the method steps described herein. These and other features of the present invention will become apparent after reviewing the detailed description of the embodiments disclosed herein. [Embodiment] In order to facilitate the understanding of the principles of the invention, the description of the specific embodiments of the invention are set forth. However, it is understood that the use of the specific terminology is not intended to limit the scope of the invention. Variations, further modifications, and such further advances are contemplated for the principles of the invention discussed herein, as generally recognized by those skilled in the art to which the invention pertains. -14- 201022666 It is important to note that the singular "1" and "the" include a plurality of indicators, unless the context clearly dictates otherwise. Thus, for example, reference to "a solvent" includes a plurality of such solvents, and references to "solvents" include references to one or more solvents, and those known to those skilled in the art. Effects and so on. The "about" used to modify the amount, concentration, volume, treatment temperature, treatment time, recovery or yield, flow rate, and similar numbers, and ranges thereof, in the composition of the present invention, It refers to changes in the number of quantities that may occur, for example, due to typical measurement and disposal procedures, inadvertent errors in these procedures, differences in the components used in the implementation of such methods, and similar considerations. The term "about" also encompasses the total amount which varies with time due to the formulation of a particular initial concentration or mixture, and the difference in the formulation of a particular initial concentration or mixture due to mixing or treatment. Total amount. Whether or not modified by the word "about", the scope of the patent application is hereby incorporated by reference. The term "chromatography" as used herein means a physical separation method in which the composition to be separated is distributed between two phases, one of which is fixed (stationary phase) and the other (mobile phase) is defined by one. Directional movement. The term "liquid chromatography" as used herein means that the mixture is separated by passing a fluid mixture dissolved in a "mobile phase" through a column comprising a stationary phase, which can be tested. The substance (ie, the target substance) is separated from other molecules in the mixture and is allowed to be isolated. The term "mobile phase" as used herein means a fluid liquid, a gas, -15-201022666 or a supercritical fluid 'which includes a sample to be separated and/or analyzed, and a sample that can be moved including the analyte to be tested. The solvent for the column. The mobile phase can be moved through the chromatography column, or the cassette (i.e., the container holding the stationary phase) where the analyte in the sample will interact, interact with the stationary phase, and be separated from the sample. As used herein, the term "stationary phase" means a material that is fixed in a column or cassette that selectively swells the analyte from the sample in the mobile phase by dissolving in a "mobile phase." One of the fluid mixtures is separated by a column comprising a stationary phase to separate the analyte to be measured from other molecules in the mixture and to allow isolation. The term "flash chromatography" as used herein means that the mixture is separated by a fluid mixture which is dissolved in a "mobile phase" under pressure through a column comprising a stationary phase. The analyte (ie, the target material) is separated from other molecules in the mixture and is allowed to be isolated. As used herein, the term "baud valve" means a control valve that regulates the supply of fluid from one or more (plural) sources to another location. The shuttle valve can be rotated or linearly moved to move the same fluid from one fluid to another. The term "fluid" as used herein means a gas, liquid, and supercritical fluid. As used herein, the term "laminar flow" means a smooth, regular movement of a fluid without any turbulence, and any given subcurrent will move nearly parallel to any other nearby submerged flow. As used herein, the term "substantially" means within a reasonable amount, but includes from about 〇% to about 50%, from about 〇% to about 40%, from -16 to 201022666, from about 0% to about 30. %, from about 0% to about 20%, or from about 0% to about 10%. The present invention is directed to a method of analyzing a sample and collecting sample components. The invention is further directed to an apparatus capable of analyzing a sample and collecting sample components. The present invention is further directed to computer software suitable for use in a device or a plurality of device components capable of analyzing a sample and collecting sample components, wherein the computer software allows the device to perform one or more of the method steps described herein. # The following is a description of an exemplary analytical sample method and equipment capable of analyzing the sample. I. Method of Analyzing Samples The present invention is directed to a method of analyzing a sample and collecting sample components. This method of analysis can include several process steps, some of which are described below. A. Actively Controlling Fluid Flow to a Detector In some embodiments of the present invention, the method of the present invention includes a φ step that includes actively controlling flow to a detection via a split pump or a shuttle valve Fluid. Figure 1 shows an exemplary liquid chromatography system depicting one of the method steps. As shown in FIG. 1, an exemplary liquid chromatography system 10 includes (i) a chromatography column n, (ii) a three-way valve 12 having a first inlet 21 and a first outlet 22. And a second outlet 23, (iii) - a component collector 14 in fluid communication with the first outlet 22 of the three-way valve 12, (iv) - a first detector 13 and a second of the three-way valve 12 The outlet 23 is in fluid communication, and (v)-split pump 15 is positioned to be in fluid communication with the second outlet -17-201022666 23 of the three-way valve 12 and the first detector 13. In the exemplary system, the splitter pump 15 can actively control the flow of fluid to the first detector 13. In this context, the term "active control" refers to the ability of a given split or shuttle valve to control the flow of fluid through a given detector, even if the fluid flow rate is in other parts of the liquid chromatography system. The same is true when there is a change. Unlike a "passive" fluid splitter that only diverts fluid, the splitter and shuttle valve used in the present invention control the flow of fluid to at least one detector, regardless of the flow resistance within the liquid chromatography system, Possible fluctuations in fluids such as total flow rate, temperature, and/or solvent composition. The step of actively controlling the flow of fluid to a given detector may include, for example, transmitting an actuation signal to the split pump or shuttle valve to (i) actuate the split or shuttle valve, (ii) deactivate The split or shuttle valve, (iii) alter one or more flow and/or pressure settings of the split or shuttle valve, or (iv) any combination of (i) through (iii). Suitable flow and pressure settings include, but are not limited to, (i) a valve position, (ii) a split pump or shuttle valve pressure, (iii) a pressure to a valve 0, or (iv) the (1) to (iii) Any combination. Typically, the actuation signal is, for example, an electrical signal, a pneumatic signal, a digital signal, or a wireless signal. As shown in FIG. 1, in the exemplary liquid chromatography system 10, the step of actively controlling the flow of fluid to the detector 13 includes using a split pump 15 to draw fluid from the three-way valve 12. Go to the detector 13. In other embodiments, the step of actively controlling the flow of fluid to a detector may include using a split pump to pull the fluid through a detector. The architecture of this system -18- 201022666 is shown in Figure 2. 2 depicts an exemplary liquid chromatography system 20 including a chromatography column 11; a three-way valve 12 having a first inlet 21, a first outlet 22, and a second outlet 23; 14. In fluid communication with the first outlet 22 of the three-way valve 12; the first detector 13 in fluid communication with the second outlet 23 of the three-way valve 12; and the split runner 15, positioned to be self-operating from the three-way valve 12 The second outlet 23 pushes the fluid through the detector 13. In some desirable embodiments, a shuttle valve such as the exemplary shuttle valve 151 shown in Figures 3A through 3C is used to actively control flow to, for example, a detector 131. Fluid. As shown in Figure 3A, an exemplary liquid chromatography system 30 includes a chromatography column 11; a shuttle valve 151 having a chromatography cartridge inlet 111, a component collector outlet 114, a gas or liquid An inlet 115 and a detector outlet 113; a component collector 14 in fluid communication with the component collector outlet 114 of the shuttle valve 151; a first detector 131, and a detector outlet 113 of the shuttle valve 151 are fluid Connected; φ and a fluid supply 152 provide a gas or liquid inlet 1 15 to the shuttle valve 151. In still another exemplary embodiment of the present invention, a method of analyzing a fluid sample using chromatography comprises providing a first fluid flowing from a chromatography column; providing a second fluid, The fluid sample is transported to at least one detector; a shuttle valve is used to remove an entire fluid sample from the first fluid, and the whole is transferred to the second fluid while maintaining the second fluid through the shuttle valve One continuous path; use at least one detector to observe -19-201022666 of the fluid aliquot; and one of the reaction-detector reactions' to collect a new sample component of the first fluid in a component collection In the device. In one embodiment, when the fluid aliquot is removed from the first fluid, the continuous flow path of the first fluid through the shuttle valve will remain. In another embodiment, when the fluid aliquot is removed from the first fluid and transported to the second fluid, both the first fluid and the second fluid pass through the continuous flow path of the shuttle valve, Will be maintained. In another exemplary embodiment in accordance with the invention, a method of analyzing a fluid sample using a chromatographic method comprises providing a first fluid comprising one of the samples; using the shuttle valve from the first fluid Removing an entire fluid sample without substantially affecting flow characteristics of the first fluid passing through the shuttle valve; using at least one detector to observe the entire fluid sample; and reacting one of the at least one detector sample Varying, the new sample component of one of the first streams is collected in a component collector. Based on the first fluid path or passageway passing substantially linearly or straightly through at least a portion of the valve, the flow of the first fluid through the shuttle valve may be substantially laminar. In yet another exemplary embodiment, the pressure of the first fluid through the shuttle valve remains substantially constant and/or substantially does not increase. In another embodiment, the flow rate of the first fluid through the shuttle valve can be substantially constant. In an alternate embodiment, a second fluid can be applied from the shuttle valve to the detector. The flow of the second fluid through the shuttle valve may be substantially laminar based on the second fluid path or passageway passing substantially linearly or straightly through at least a portion of the valve. In an exemplary embodiment, the pressure of the second fluid through the shuttle valve is approximately -20-201022666, and/or it does not substantially increase. In another embodiment, the flow rate of the second fluid through the shuttle valve can be substantially constant. Figures 3B and 3C depict how a shuttle valve in an exemplary embodiment operates in a given liquid chromatography system. As shown in Figure 3B, the shuttle valve 151 includes a chromatography cassette inlet 111 that provides fluid flow from a chromatography column (e.g., column 11) to the shuttle valve 151; - external access to the sample aliquot 116; a component collector outlet 114 that provides fluid flow from the shuttle valve 151 to a component collector (eg, component collector 14); a gas or liquid φ body inlet 115 that provides gas (eg, air, nitrogen, etc.) , or a liquid (for example, an alcohol) flows through a portion of the shuttle valve 151; a discharge sample split body 117; and a detector outlet 113 that provides fluid flow from the shuttle valve 151 to a detector (for example, A detector 131, such as an Evaporative Light Scattering Detector (ELSD). When fluid flows from the chromatography cartridge inlet 111 through the shuttle valve 151 to the component collector outlet 114, the foreign incoming sample aliquot 116 will be filled with a φ specific volume of fluid, referred to herein as a sample integral 118 (eg, The shaded area in Figure 3B is displayed). At a desired time, the shuttle valve 151 can transfer the sample fraction 118 that is externally introduced into the sample aliquot 116 into the expelled sample aliquot 7, as shown in Figure 3C. Once the sample fraction 118 is transported into the expelled sample aliquot 117, the sample aliquot 118 is transmitted from the inlet 115 to the Detector 13 via the Detector Outlet 113 by flowing the gas or liquid exiting the sample plough 117 from the inlet 115. 1 (for example, an evaporative light scattering detector). The shuttle valve 151 can be programmed to remove the same integral (e.g., sample -21 - 201022666 this integral 118) from the same and transmit to at least one detector at a desired sampling frequency. In an exemplary embodiment, the sampling frequency is at least 1 sample aliquot every 10 seconds (s) (or at least 1 sample aliquot every 5 seconds, or at least 1 sample aliquot every 3 seconds, or at least 2 samples per 2 seconds 1 sample whole, or every 0. At least 1 sample in 5 seconds, or every 0. At least 1 sample in 1 second). Figures 10A through 10C depict an exemplary shuttle valve of the present invention and how it operates in a given liquid chromatography system. As shown in FIG. 10A, the shuttle valve 151 includes a chromatography cassette inlet 111 that provides fluid flow from a chromatography column (eg, column 11) to the shuttle valve 151; passage 117, connection Inlet 111 to outlet 114; externally entering sample aliquot 118, located in a dimple 116 of a dynamic body 119; component collector outlet 114, which provides fluid flow from shuttle valve 151 to a component collector (e.g., composition) a collector 14); a gas or liquid inlet 115, which may provide a gas (for example, air, nitrogen), or a liquid (for example, an alcohol) through the shuttle valve 151; and discharge the sample aliquot 118 in the pocket 116; a passage 120 connecting the inlet 115 to the outlet 113; φ and the detector outlet 113, which can supply fluid flow from the shuttle valve 151 to a detector (for example, the detector 113, such as an evaporative light scattering detection) Device). When fluid flows from the chromatography cartridge inlet 111 through the channel 117 through the shuttle valve 151 to the component collector outlet 114, the sample into the sample aliquot 118 will be filled with a specific volume of fluid, referred to herein as Divide 1 18 for the sample (as shown by the shaded area in Figure 10A). At a desired time, the shuttle valve 151 can rotate the path 116 in the dynamic body 119 through a pit rotation path 121, and the pit 116 taken from the channel 117 can be sampled -22-201022666. 118 is transferred to channel 120. Once the sample fraction 118 is transported to the gas or liquid flowing through the channel 120 from the inlet 115 in the channel 120, the sample fraction 118 can be transmitted via the detector outlet 113 to the detector 131 (eg, an evaporative light scattering assay) Checker). Another advantage of the shuttle valve of the present invention relates to the jet design through the passage of the valve. In order to minimize back pressure in the chromatography system, the flow through channels 117 and 120 is continuous. This can be achieved by positioning channels 117 and 120 on a static body. 122, such that regardless of the position of the dynamic body 119, the flow through the shuttle valve 151 is continuous (as shown in Figure 10B). As shown in Figure 10A, at least a portion of the sample stream channel 117 and the detector stream channel 120 can be generally planar or circumferential, which reduces turbulence and further minimizes pressure build-up through the valve. In addition, at least a portion of the sample stream channel 1 17 and the detector stream channel 120 may be substantially parallel to the pit when it is continuous with the pit 116, thereby further limiting the turbulence and the valve Any pressure increases. This includes not increasing the pressure within the valve by more than 50 psi, preferably no more than 30 psi, more preferably no more than 20 psi, and even more preferably no more than 10, 9, 8, 7, 6 , 5, 4, 3, 2, or lpsi architecture. The dimple 116 is located in the dynamic body 119 and is in fluid communication with the dynamic body surface adjacent the static body 122, whereby the dimple 116 will be associated with the sample stream channel when the dynamic body 119 is in a first position. In fluid communication, and when moved to a second position, the dimples 116 will be in fluid communication with the detector flow channel 120. The dimple 116 can be of any shape, but is depicted as a concave hemisphere and can be of any size. In an exemplary embodiment, the size of the dimple can be extremely small (e.g., less than 2000 nanoliters (nL), preferably less than about 500 nL, more preferably less than about 100 nL, and even less than about InL. , but may include any size that allows fast sampling of InL to 2000nL). In addition, the small dimple 116 is sized to allow a very short dimple rotation path 121, which greatly reduces wear on the surfaces of the dynamic body 119 and the static body 122, and causes the shuttle valve 151 to be extended before it is repaired. Service life (for example, may exceed 10 million operating cycles before overhaul). Only a rotary motion shuttle valve, a linear motion shuttle valve, or its equivalent, can be used in the present invention, as shown in Figs. 10A to 10C. The shuttle valve 151 can be programmed to move from the same division (e.g., sample integral 118) and to at least one detector at a desired sampling frequency. In an exemplary embodiment, the sampling frequency is at least 1 sample aliquot per 10 seconds (or at least 1 sample aliquot every 5 seconds, or at least 1 sample aliquot every 3 seconds, or at least 1 sample every 2 seconds Whole points, or every 0. 5 seconds at least 1 sample whole, or every 0. At least 1 sample in 1 second). The shuttle valve is further described in the co-pending U.S. Provisional Patent Application Serial No., the entire contents of which are incorporated herein by reference. In another embodiment, the chromatography system can be transported to a detector using a universal carrier fluid containing volatile liquids and various gases. As shown in Figure 3A, the carrier fluid from the fluid supply device 152 will enter the shuttle valve 151 at its inlet 115 of the sample split 118 (shown in Figure 10A), and then through the outlet 113. Proceed to the detector 131. The sample aliquot should not precipitate in the carrier fluid of the valve, or -24-201022666 to cause the associated piping to become clogged, or to apply the sample to the wall of the flow path, and some or all of the sample Unable to reach the spy. The sample composition in rapid chromatography can be very diverse, and covers a wide range of chemical compounds including inorganic molecules, organic molecules, polymers, peptides, proteins, and oligonucleic acids. The solubility in various solvents is different regardless of the same type of compound and between different compounds. The compatibility of the detector also limits the type of carrier fluid that can be used. For example, for ultraviolet (UV) detection, the solvent should not be colored at the detection wavelength. For evaporative particle detection (EPD) ❿ technology (evaporative light scattering detector, condensed nucleation light scattering detector, mass spectrometer, etc.), the solvent should be easily at a temperature that is considerably lower than the melting point of the sample, easily evaporation. Alternatively, the carrier fluid should be miscible with the sample flowing between the valve inlet 111 and the component collector outlet 114. For example, if hexane is used in a certain flow path, hexane and water cannot be miscible, so that water cannot be used in another flow path. All of the above suggests that the carrier fluid should be customized for each change in solvent separation. This will be time consuming and impractical. According to an exemplary embodiment of the present invention, the use of a solvent which is miscible with an organic solvent and water, which is volatile and non-ferrous, will avoid this problem. For example, a volatile, non-carrier, polar solvent such as isopropyl alcohol (IPA) can be used as the carrier fluid. IPA is miscible with almost all solvents, does not color at normal UV detection wavelengths, and evaporates easily at low temperatures. In addition, IPA dissolves a wide range of chemicals and chemical classes. Therefore, IPA is a suitable carrier fluid for almost all sample types. Other carrier fluids may include acetone, methanol, ethanol, propanol, butanol, isobutanol, tetrahydrofuran, and -25-201022666. In an alternate exemplary embodiment, a gas can be utilized as the carrier fluid. Since the sample remains in the separation solvent or in the mobile phase as it passes through the shuttle valve and subsequently passes through the detector, no sample precipitation is encountered. Similarly, the separation solvent or mobile phase is never mixed with another solvent, so miscibility is not a problem. Since the carrier is a gas, volatility is no longer a controversial issue. In addition, most gases do not carry color and are compatible with UV detection. When a gas is used as the carrier, the sample integral 118 is discharged from the valve 151 to the detector 131, and the discrete small pieces are squeezed between the plurality of air cells 123 as shown in Fig. 10C. The use of gas as a carrier has other advantages. For example, when a sample is required to be atomized by an evaporative light scattering detector or other detection technology, the gas can be used to transport the sample and atomize the sample, eliminating the need for a separate atomizing gas supply. . In addition, since the gas does not need to be evaporated, the peripheral drift tube temperature can be used without the need for a drift tube heater. Because of the sample that can be evaporated at higher temperatures, g will now remain solid or liquid as it passes through the drift tube, thus detecting a wider sample. Various types of gases including air, nitrogen, helium, and carbon dioxide can be used as the carrier gas. Supercritical fluids such as supercritical carbon dioxide can also be used. B. Detecting a Sample Composition in a Steroid Stream The method of the present invention includes using at least one detector to detect one or more constituents within the first-class body stream. Detectors suitable for use in the liquid chromatography system of the present invention include, but are not limited to, non-destructive, and/or destructive detectors. Suitable detectors include, but are not limited to, non-destructive detectors (ie, -26- 201022666 detectors that do not consume or destroy samples during detection), such as ultraviolet light, refractive index, conductivity, fluorescent light, light Scattering, viscosity measurement, optical rotation assays, and the like; and/or destructive detectors (ie, detectors that consume or destroy samples during detection), such as, for example, evaporative light scattering detectors (ELSD) ), an Evaporation Particle Detector (EPD) such as a condensed nucleation light scattering detector (CNLSD), corona discharge, mass spectrometry, atomic absorption, and the like. For example, the apparatus of the present invention may comprise at least one ultraviolet detector, at least one evaporative light scattering detector (ELSD), at least one mass spectrometer (MS), at least one coherent nucleation light scattering detector (CNLSD), At least one corona discharge detector (CDD), at least one refractive index detector (RID), at least one fluorescent detector (FD), at least one chiral detector (CD), or any combination thereof. In an exemplary embodiment, the detector may include one or more evaporative particle detectors (EPDs) that permit the use of both color- and non-carrier solvents as the mobile phase. In yet another embodiment, a non-destructive detector can be associated with a detection property such as a chemical entity, a chemical structure, a molecular weight, etc., associated with each of the carrier peaks. A destructive detector combines. When combined with a mass spectrometer, the chemical structure and/or molecular weight of the component can be determined at the time of detection, making the identification of the desired component more efficient. In existing systems, the cumbersome post-separation technique must be used to determine the chemical characteristics and structure of the components. Regardless of the type of detector used, a given detector provides one or more detector responses that can be used to generate and transmit a signal to one or more of the liquid chromatography systems. Multiple components (for example, one component -27-201022666 collector, another detector, a split pump, a shuttle valve, or a three-way valve), as described herein. Typically, a change in a given detector response triggers the generation and transmission of a signal. In the present invention, one of the detector responses may be triggered to generate and transmit a signal to one or more components including, but not limited to, one of the detector responses, one or more, one or more a critical detector response, a slope of the detector, a slope of a period of time, a critical slope of the detector reaction, a period of time, a slope of the detector response, a change over a period of time, The slope of one of the detectors @reactions undergoes a critical change over a period of time, or any combination thereof. In certain exemplary embodiments, the liquid chromatography system of the present invention includes at least two detectors, as shown in Figure 4. An exemplary liquid chromatography system 40 shown in FIG. 4 includes a chromatography column 11; a three-way valve 12 having a first inlet 21, a first outlet 22, and a second outlet 23; a composition collector 14, The first outlet 22 is in fluid communication with the three-way valve 12; the first detector @13 is in fluid communication with the third outlet 23 of the three-way valve 12; the split pump 15 is actively controlled from the second outlet 23 of the three-way valve 12. The fluid flowing to the first detector 13; and a second detector 16 in fluid communication with the second outlet 23 of the three-way valve 12. The liquid chromatography system provides an operator with more analytical options when two or more detectors are present. For example, in the exemplary liquid chromatography system 40 shown in FIG. 4, an analytical method can include, from the first detector 13 (eg, an evaporative light scattering detector), and / Or a second detect -28-201022666 detector 16 (for example, an optical light-detecting detector, such as an ultraviolet detector) transmits one or more signals to the component collector 14 to instruct the component collector 14 to collect a new sample component One step. The one or more signals from the first detector 13 and/or the second detector 16 may include a single signal from the first detector 13 or the second detector 16 from the first signal 13 And two or more signals of the second signal 16 or a combined signal from one of the first detector 13 and the second detector 16. In the exemplary liquid chromatography system 40 shown in FIG. 4, the method of the present analysis may include the step of transmitting a signal from the second sound detector 16 to the splitter pump 15 to react to the second The detector 16 detects the same composition in a fluid stream to indicate that the split runner 15 initiates or stops fluid flow to the first detector 13. In other exemplary embodiments, the liquid chromatography system of the present invention comprises at least two detectors, and at least a two-split pump, as shown in Figure 5. An exemplary liquid chromatography system 50 shown in FIG. 5 includes a chromatography column 11; a first three-way valve 12 having a first inlet 21, a first outlet 22, and a second outlet 23; The detector 13 is in fluid communication with the second outlet 23 of the first three-way valve 12; the first branching pump 15' actively controls the fluid flowing from the second outlet 23 of the first three-way valve 12 to the first detector 13 a second three-way valve 18 having a first inlet 31, a first outlet 32, and a second outlet 33; a second detector 16' and a second outlet 33 of the second three-way valve 33 are fluid Connected; a second split runner 17, actively controlling the flow of fluid from the second outlet 33 of the second three-way valve 18 to the second detector 16; and the component collector 14, and the first outlet of the second three-way valve 18. 32 is in fluid communication. -29- 201022666 As described above, the liquid chromatography system of the present invention may include one or more shuttle valves in place, or one or more three-way valve/shunt pump compositions to actively control fluids Flow to at least one detector, as exemplified in Figures 6 through 7. As shown in FIG. 6, an exemplary liquid chromatography system 60 includes a chromatography column 11; a shuttle valve 151 having a chromatography cartridge inlet 111, a component collector outlet 114, a gas or liquid inlet 115, and a detector outlet 113; a component collector 14 in fluid communication with a component collector outlet 114 of the shuttle valve 151; a first detector 131 in fluid communication with the shuttle valve 151 and a detector outlet 113; a fluid supply device 152, providing a fluid or liquid inlet 115 to the shuttle valve 151; and a second detector 161 in fluid communication with the detector outlet 113 of the shuttle valve 151. As shown in Figure 7, an exemplary liquid chromatography system 70 includes a chromatography column 11; a first shuttle valve 151 having a chromatography cartridge inlet 111, a component collector outlet 114, a gas or liquid inlet 115. And the detector outlet 113; the first detector 131 is in fluid communication with the detector outlet 113 of the shuttle valve 151; the fluid supply device 152 provides a gas or liquid inlet 115 to the shuttle valve 151; The second shuttle valve 171 has a chromatography cartridge inlet 121, a component collector outlet 124, a gas or liquid inlet 125, and a detector outlet 123; a second detector 161, and a shuttle valve 171 The detector outlet 123 is in fluid communication; a fluid supply device 172, a gas or liquid inlet 125 that provides fluid to the shuttle valve 171; and a component collector 14 in fluid communication with the component collector outlet 124 of the shuttle valve 171. In these exemplary embodiments, namely the exemplary liquid chromatography system 50 and -30-9

201022666 70中,一種分析一樣本之方法可尙包括主動地控制i 由第二分流泵17(或第二梭閥171)流動至第二偵檢器 第二偵檢器161)、以及主動地控制流體經由第一分 15(或第一梭閥151)流動至一偵檢器13(或第一偵檢器 的一步驟。僅管第5圖中未顯示出,然應了解到,第 流泵15、及/或第二分流泵17可定位於例示性液相層 統50內,以推動或拉拖流體分別通過第一偵檢器13 二偵檢器16。 在某些例示性實施例中,可使用譬如一個或更 線偵檢器等一個或更多光學吸光偵檢器,來觀察橫 頻譜之一個或更多波長下的偵檢器反應、及偵檢器 變化。在這些實施例中,可結合一單一偵檢器或多 器內之多重感測器,使用一個或更多光源,來偵檢 在多重波長下之吸光度。例如,可使用一個或更多 偵檢器來觀察橫跨整個紫外線吸光頻譜之一個或更 下的偵檢器反應、及偵檢器反應之變化。 在某一例示性之分析樣本方法中,該方法之 括:使用一紫外線偵檢器等一光學吸光偵檢器,該 包括η個感測器’而以橫跨整個紫外線吸光頻譜之 定波長來觀察一樣本;及(i)反應η個特定紫外線波 η個偵檢器反應中任一個的一變化,或(ii)由η個偵 應所表達之一組合反應中的一變化,收集一新的 分。當存有η個感應器及多重偵檢器時,該等者可 體經 16(或 流泵 131) 一分 析系 與第 紫外 吸光 應之 .偵檢 樣本 1外線 •波長 驟包 【檢器 個特 i下之 Ϊ器反 丨本成 ^需要 -31- 201022666 而互相相對地定位,以影響一成分收集器及/或其他系統組 件(譬如,其他紫外線偵檢器)之信號時序。 當利用全譜紫外線(或其他頻譜範圍)分析時,其頻譜 可劃分成有興趣的任何數量之範圍(譬如,200毫微米(nm) 至400nm範圍內之每5nm)。可監測到經歷一段時間下,在 每一頻譜範圍中之任何顯著變化。接收到之光線能量在一 給定範圍內之一突降(譬如,在偵檢器反應之一階與二階導 數二者中的一下降)係指示出,可吸收該有興趣之給定波長 m 範圍內的光線之一物質已到來。在例示性實施例中,可使 每一範圍之寬度更小,以提高精確度;另一選擇爲,每一 範圍之寬度可更大,以減少計算負荷(β卩,每秒之計算量、 記憶體等需求較小)。 在其他例示性實施例中,可使用複數個不同型態之偵 檢器,來觀察一給定系統內之各式各類偵檢器反應、及該 等偵檢器反應中之變化。在第8圖所顯示出之一例示性液 0 相層析系統80中,可僅單獨使用譬如一蒸發光散射偵檢器 (ELSD)等之一蒸發微粒偵檢器(EPD)(即第一偵檢器13),或 與一紫外線偵檢器(即,第二偵檢器16)結合使用。例示性 液相層析系統80尙包括層析管柱11;三通閥12,具有第 一進口 21、第一出口 22、及第二出口 23;成分收集器14; 蒸發微粒偵檢器13,與三通閥12之第二出口 23以流體連 通;分流泵15,主動地控制流動至蒸發微粒偵檢器13之流 體;及紫外線偵檢器16,與三通閥12之第一出口 22以流 -32- 201022666 體連通。在本例示性實施例中,使用蒸發微粒偵檢器可提 供數個優點。非載色移動相必須結合紫外線偵檢使用,或 著該移動相之背景吸光可消除該樣本信號。如此可排除使 用譬如甲苯、吡啶、及具有其餘有用載色特性之其他者等 溶劑。藉由蒸發微粒偵檢者,移動相載色特性係無關緊要。 只要移動相較該樣本更具揮發性,其即可結合蒸發微粒偵 檢使用。如此可經由使用高度敏感之載色溶劑作爲移動 相’而開啓改善分離之機會。此外,紫外線偵檢器將無法 偵檢非載色樣本組成物。僅根據紫外線偵檢爲基礎而收集 到之成分可包含有一個或更多無法鑑別之非載色組成物, 如此需與成分純度妥協。相反地,非載色樣本將爲紫外線 偵檢所完全遺漏,且直接認定爲廢棄物、或收集成認定爲 無樣本之成分(無成分)》最終結果爲損失生產率、污染成 分、或損失有用之樣本組成物。當在快速系統中單獨、或 結合紫外線偵檢來運用一蒸發微粒偵檢器(譬如,蒸發光散 @ 射偵檢器)時,可偵檢及收集載色與非載色組成物,而改善 成分純度。由於僅單獨包含紫外線偵檢器之一快速系統可 遺漏樣本組成物、或不正確地標示其爲純淨成分,因此許 多快速系統使用者將藉薄層層析篩選收集到之成分,來確 認純度、及確認無成分是否屬實。此爲減慢工作流程速度 之一耗時的後分離程序。已發現到包含有超過一種組成物 之成分,經常需一第二層析步驟來適恰地離析該等組成物。 在例示性液相層析系統80中,可將分別來自偵檢器(譬 -33- 201022666 如蒸發光散射偵檢器)13與紫外線偵檢器16之信號31與 61,送至成分收集器14中,以啓始譬如收集一新樣本成分 等始於成分收集器14之某些活動。在期望之實施例中,成 分收集器14可反應來自(i)偵檢器蒸發光散射偵檢器13、 紫外線偵檢器16、或(iii)蒸發光散射偵檢器13及紫外線偵 檢器16二者之一個或更多偵檢器信號31及61,收集一新 樣本成分。 相似於例示性液相層析系統80,在第6圖中所顯示之 例示性液相層析系統60中,可將分別來自蒸發光散射偵檢 器131與紫外線偵檢器161之信號311與611,送至成分收 集器14中,以啓始譬如收及一新樣本成分等始於成分收集 器14之某些活動。在期望之實施例中,成分收集器14可 反應來自(i)蒸發光散射偵檢器131、(ii)紫外線偵檢器161、 或(iii)蒸發光散射偵檢器131及紫外線偵檢器161二者之一 個或更多偵檢器信號311及611,收集一新樣本成分》 如上所述,紫外線偵檢器16(或紫外線偵檢器161)可包 括η個感測器,作動式地調整成適應於,在橫跨一部份或 整個紫外線吸光頻譜之η個特定波長下,觀察一樣本。在 第8圖中所顯示之例示性液相層析系統80中,成分收集器 14可反應(i)來自蒸發光散射偵檢器13或紫外線偵檢器16 任一個之一單一信號,(ii)來自蒸發光散射偵檢器13及紫 外線偵檢器16二者之二個或更多信號,或(iii)包括在二個 或更多特定紫外線波長(即,可達η個特定紫外線波長)下 -34- 201022666 之二個或多偵檢器反應的一組合信號,收集一新樣本成 分。相似地,在第6圖中所顯示之例示性液相層析系統60 中,成分收集器14可反應(i)來自蒸發光散射偵檢器131 或紫外線偵檢器161任一個之一單一信號,(Π)來自蒸發光 散射偵檢器131及紫外線偵檢器161二者之二個或更多信 號,或(iii)包括在二個或更多特定紫外線波長(即,可達η 個特定紫外線波長)下之二個或多偵檢器反應的一組合信 號,收集一新樣本成分。 參 更,在例示性液相層析系統80中,紫外線偵檢器16 可用於產生一偵檢器信號(未顯示),其(1)起始於⑴來自一 單一感測器之一單一偵檢器反應、或(ii)來自η個感測器之 η個偵檢器反應且其中η大於1,及(2)傳送至分流泵15、 蒸發光散射偵檢器13、及三通閥12至少其中之一。另,起 始於蒸發光散射偵檢器13中之一偵檢器反應的一偵檢器 信號,可傳送至紫外線偵檢器16,以改變紫外線偵檢器16 〇 之一個或更多設定。相似地,在第6圖中所顯示之例示性 液相層析系統60中,紫外線偵檢器161可用於產生一偵檢 器信號(未顯示),其(1)起始於⑴來自一單一感測器之一單 一偵檢器反應、或(ii)來自η個感測器之n個偵檢器反應且 其中η大於’及(2)傳送至梭閥151及蒸發光散射偵檢器13 至少其中之一。另,起始於蒸發光散射偵檢器131中之一 偵檢器反應的一偵檢器信號,可傳送至紫外線偵檢器161, 以改變紫外線偵檢器161之一個或更多設定。 -35- 201022666 如第9圖中所顯示之一例示性液相層析系統90中所顯 示者,可依期望調整不同型態之偵檢器在一給定系統內的 位置,以提供一個或更多系統處理特點。在例示性液相層 析系統90中,蒸發光散射偵檢器13係定位於紫外線偵檢 器16之下游。在這種配置下,紫外線偵檢器16係定位成, 使其能夠提供一偵檢器反應,及在來自蒸發光散射偵檢器 13之信號31生成前,生成成分收集器14用信號61(譬如, 起始於(i)來自一單一感測器之一單一偵檢器反應、或(ii) 來自η個感測器之η個偵檢器反應且其中η大於1的一信 號)。紫外線偵檢器16亦定位成,使其能夠提供一偵檢器 反應,及生成供分流泵15、蒸發光散射偵檢器13、及三通 閥12至少其中之一用的一信號(譬如,起始於⑴來自一單 —感測器之一單一偵檢器反應、或(ii)來自η個感測器之η 個偵檢器反應且其中η大於1的一信號),以致動或解除致 動分流泵15、蒸發光散射偵檢器13、及/或三通閥12。 φ 儘管未顯示出,然請了解到,在第9圖中所顯示之例 示性液相層析系統90內,可使用一梭閥來取代三通閥12 及分流泵15,以提供相似之處理特點。在這種配置下,紫 外線偵檢器16係定位成,使其能夠提供一偵檢器反應,及 在來自蒸發光散射偵檢器13之信號31生成前,生成成分 收集器14用信號61 (譬如,起始於(i)來自一單一感測器之 一單一偵檢器反應、或(ii)來自η個感測器之η個偵檢器反 應且其中η大於1的一信號)。紫外線偵檢器16亦定位成, -36- 201022666 使其能夠提供一偵檢器反應,及生成供一梭閥及蒸發光散 射偵檢器13至少其中之一用的一信號(譬如,起始於(i)來 自一單一感測器之一單一偵檢器反應、或(ii)來自η個感測 器之η個偵檢器反應且其中η大於1的一信號),以致動或 解除致動該梭閥及/或蒸發光散射偵檢器13。儘管系統60、 80、及90係提及以蒸發光散射偵檢器及紫外線作爲偵檢 器,然譬如蒸發微粒偵檢器等任何破壞性偵檢器仍可用作 爲蒸發光散射偵檢器,且可運用任何非破壞性偵檢器來取 鲁 代紫外線偵檢器。 在其他例示性實施例中,本發明之液相層析系統可包 括一非破壞性系統,其包括二個或更多非破壞性偵檢器(譬 如,一個或更多光學吸光偵檢器,如上述之紫外線偵檢 器),且該系統中不存有任何破壞性偵檢器(譬如,一質譜 儀)。在某一例示性實施例中’該液相層析系統包括譬如紫 外線偵檢器等二光學吸光偵檢器’且分析一樣本之方法的 φ 步驟包括:使用二個或更多偵檢器’而在二個或更多特定 波長下觀察一樣本;及反應(i) 一第一偵檢器反應在一第 一波長下之一變化’(ii)一第二偵檢器反應在一第二波長下 之一變化,或(iii)該第一偵檢器反應與該第二偵檢器反應 所表達之一組合反應中的—變化’收集一新樣本成分。在 這些實施例中,該第一波長可與該第二波長大致相同或不 同。 在運用譬如二個或更多紫外線偵檢器等二個或更多光 -37- 201022666 學吸光偵檢器之實施例中,該等光學吸光偵檢器可於一給 定液相層析系統內定位,以提供一個或更多系統優點。該 二個或更多光學吸光偵檢器可相互地以一平行關係定位, 使得一樣本於大致相同時間到達每一偵檢器,且該二個或 更多光學吸光偵檢器可於大i相同時間產生及傳送信號 (即,來自第一偵檢器及第二偵檢器反應)至一成分收集器。 在又一實施例中,可單獨、或結合一破壞性偵檢器(譬 如’蒸發微粒偵檢器EPD、質譜儀、光譜儀、發射光譜法、 核磁共振(NMR)等),使用一非破壞性偵檢器(譬如,折射率 RI偵檢器、紫外線偵檢器等)。例如,譬如一質譜儀偵檢器 等一破壞性偵檢器,可允許同時偵檢組成物峰値、及關聯 於該峰値之化學個體。如此將容許立即決定出包含有目標 化合物之成分。使用其他偵檢技術時,需要藉譬如分光光 度法、質譜測定法、發射光譜法、核磁共振等,來實施關 於哪一成分包含有目標化合物之後分離判定。倘二個或更 φ 多化學個體同時自快速卡匣洗提(即,具有相同的滯留時 間),則當使用某些特定偵檢器(即,無法鑑別該等化學個 體之間差異的偵檢器)時,將因該等偵檢器無法決定化學組 成物,而由該系統使該等者沉積於相同小瓶中。在一質譜 儀偵檢器用作爲該破壞性偵檢器之一例示性實施例中,可 鑑別出同時洗提之所有化合物。如此將可免除分離後再確 認純度之需求。In 201022666 70, an analytical method may include actively controlling i to flow from the second split pump 17 (or the second shuttle valve 171) to the second detector second detector 161), and actively controlling The fluid flows to the detector 13 via the first minute 15 (or the first shuttle valve 151) (or a step of the first detector). Although not shown in Figure 5, it should be understood that the first flow pump 15, and/or a second split pump 17 may be positioned within the exemplary liquid level system 50 to push or pull the tow fluid through the first detector 13 and the second detector 16 respectively. In certain exemplary embodiments One or more optical absorbance detectors, such as one or more line detectors, may be used to observe the detector response and detector changes at one or more wavelengths of the transverse spectrum. In these embodiments Can be combined with a single detector or multiple sensors within a multi-sensor to detect absorbance at multiple wavelengths using one or more sources. For example, one or more detectors can be used to observe the span. One or more of the entire UV absorption spectrum, the detector response, and the detector response In an exemplary analytical sample method, the method includes: using an optical ray detector such as an ultraviolet detector, the η sensor is included to straddle the entire ultraviolet absorption spectrum Wavelength to observe the same; and (i) reacting a change in any of the n specific UV wave η detector responses, or (ii) collecting a change in one of the combined reactions expressed by n Detectors, collecting A new point. When there are η sensors and multiple detectors, the person can pass through 16 (or flow pump 131) an analysis system and the first ultraviolet light absorption. Detection sample 1 outside line • wavelength The package [checks the device under the special i 丨 丨 ^ ^ -31- 201022666 and is positioned relative to each other to affect the signal of a component collector and / or other system components (such as other ultraviolet detectors) Timing. When using full-spectrum UV (or other spectral range) analysis, the spectrum can be divided into any number of ranges of interest (for example, every 5 nm in the range of 200 nanometers (nm) to 400 nm). For a while, at every Any significant change in the spectral range. A sudden drop in the received ray energy over a given range (for example, a decrease in both the first and second derivatives of the detector response) is indicated by One of the sources of light that absorbs the range of interest for a given wavelength m has arrived. In an exemplary embodiment, the width of each range can be made smaller to improve accuracy; another option is that each range The width can be larger to reduce the computational load (β卩, calculations per second, memory, etc.). In other exemplary embodiments, a plurality of different types of detectors can be used to observe one. Various types of detector responses within a given system, and changes in the response of such detectors. In an exemplary liquid phase 0 chromatography system 80 shown in Figure 8, it may be used alone. An Evaporative Light Scatter Detector (ELSD) or an Evaporative Particle Detector (EPD) (ie, the first Detector 13), or used in conjunction with an Ultraviolet Detector (ie, the Second Detector 16) . The exemplary liquid chromatography system 80A includes a chromatography column 11; a three-way valve 12 having a first inlet 21, a first outlet 22, and a second outlet 23; a component collector 14; an evaporative particle detector 13, The second outlet 23 of the three-way valve 12 is in fluid communication; the split pump 15 actively controls the flow of fluid to the evaporative particle detector 13; and the ultraviolet detector 16, and the first outlet 22 of the three-way valve 12 Stream-32- 201022666 Body connectivity. In the present exemplary embodiment, the use of an evaporative particle detector provides several advantages. The non-carrier mobile phase must be used in conjunction with UV detection, or the background absorption of the mobile phase can eliminate the sample signal. This eliminates the use of solvents such as toluene, pyridine, and others having the remaining useful color loading characteristics. By evaporating the particle detector, it is irrelevant to move the phase-carrying color characteristics. As long as the mobile phase is more volatile than the sample, it can be used in conjunction with evaporative particle detection. This opens up the opportunity to improve separation by using a highly sensitive carrier solvent as the mobile phase. In addition, the UV detector will not be able to detect non-carrier sample components. The ingredients collected on the basis of UV detection alone may contain one or more unidentifiable non-carrier compositions, which are to be compromised with the purity of the ingredients. Conversely, non-carrier samples will be completely missed by UV detectors and directly identified as waste, or collected as ingredients without ingredients (no ingredients). The end result is useful for loss of productivity, pollution, or loss. Sample composition. When using an evaporative particle detector (such as evaporative light scattering detector) in a fast system or in combination with UV detection, it can detect and collect both color and non-carrier components, and improve Ingredient purity. Since only one of the UV detectors alone can miss the sample composition or incorrectly mark it as a pure component, many rapid system users will use thin layer chromatography to screen the collected components to confirm purity, And confirm that no ingredients are true. This is a time-consuming post-separation program that slows down the workflow. It has been found that components containing more than one composition often require a second chromatography step to properly isolate the compositions. In the exemplary liquid chromatography system 80, signals 31 and 61 from the detector (譬-33-201022666 such as evaporative light scattering detector) 13 and ultraviolet detector 16 may be sent to the component collector. In 14th, some activities starting from the component collector 14 are initiated, such as collecting a new sample component. In a preferred embodiment, the component collector 14 can be reacted from (i) the detector evaporative light scattering detector 13, the ultraviolet detector 16, or (iii) the evaporative light scattering detector 13 and the ultraviolet detector. 16 One or more of the detector signals 31 and 61 collect a new sample component. Similar to the exemplary liquid chromatography system 80, in the exemplary liquid chromatography system 60 shown in FIG. 6, the signals 311 from the evaporative light scattering detector 131 and the ultraviolet detector 161, respectively, can be 611, sent to the ingredient collector 14 to initiate certain activities, such as receiving a new sample component, starting from the component collector 14. In a preferred embodiment, component trap 14 can be reacted from (i) evaporative light scattering detector 131, (ii) ultraviolet detector 161, or (iii) evaporative light scattering detector 131 and ultraviolet detector 161 one or more of the detector signals 311 and 611, collecting a new sample component. As described above, the ultraviolet detector 16 (or the ultraviolet detector 161) may include n sensors, actually Adjusted to accommodate the observation of the same at n specific wavelengths across a portion or the entire ultraviolet absorption spectrum. In the exemplary liquid chromatography system 80 shown in Fig. 8, the component collector 14 can react (i) a single signal from either of the evaporative light scattering detector 13 or the ultraviolet detector 16, (ii) Two or more signals from both the evaporative light scattering detector 13 and the ultraviolet detector 16, or (iii) included in two or more specific ultraviolet wavelengths (ie, up to n specific ultraviolet wavelengths) A combined signal of two or more detector responses of -34-201022666 collects a new sample component. Similarly, in the exemplary liquid chromatography system 60 shown in FIG. 6, the component collector 14 can react (i) a single signal from either of the evaporative light scattering detector 131 or the ultraviolet detector 161. , (Π) two or more signals from both the evaporative light scattering detector 131 and the ultraviolet detector 161, or (iii) included in two or more specific ultraviolet wavelengths (ie, up to n specific A combined signal of two or more detectors under the ultraviolet wavelength) collects a new sample component. In addition, in the exemplary liquid chromatography system 80, the ultraviolet detector 16 can be used to generate a detector signal (not shown), which (1) begins with (1) a single detection from a single sensor. Detector reaction, or (ii) n detector responses from n sensors and wherein η is greater than 1, and (2) transmitted to shunt pump 15, evaporative light scattering detector 13, and three-way valve 12 At least one of them. Alternatively, a detector signal that begins with one of the detectors in the evaporative light scattering detector 13 can be transmitted to the ultraviolet detector 16 to change one or more settings of the ultraviolet detector 16 。. Similarly, in the exemplary liquid chromatography system 60 shown in Figure 6, the ultraviolet detector 161 can be used to generate a detector signal (not shown), starting at (1) from a single One of the sensors reacts with a single detector, or (ii) n detectors from the n sensors and wherein n is greater than ' and (2) is transmitted to the shuttle valve 151 and the evaporative light scattering detector 13 At least one of them. Alternatively, a detector signal originating from one of the detectors in the evaporative light scattering detector 131 may be transmitted to the ultraviolet detector 161 to change one or more settings of the ultraviolet detector 161. -35- 201022666 As shown in one of the exemplary liquid chromatography systems 90 shown in Figure 9, the position of the different types of detectors within a given system can be adjusted as desired to provide one or More system processing features. In the exemplary liquid phase stratification system 90, the evaporative light scattering detector 13 is positioned downstream of the ultraviolet detector 16. In this configuration, the ultraviolet detector 16 is positioned such that it provides a detector response and generates a component collector 14 with a signal 61 prior to generation of the signal 31 from the evaporative light scattering detector 13. For example, starting with (i) a single detector response from a single sensor, or (ii) a signal from n detectors of n sensors and where n is greater than one). The ultraviolet detector 16 is also positioned to provide a detector response and to generate a signal for at least one of the split pump 15, the evaporative light scattering detector 13, and the three-way valve 12 (e.g., Starting from (1) a single detector response from a single-sensor, or (ii) a signal from n detectors of n sensors and where n is greater than 1) to actuate or deactivate The split pump 15, the evaporative light scattering detector 13, and/or the three-way valve 12 are actuated. φ Although not shown, it is understood that in the exemplary liquid chromatography system 90 shown in Figure 9, a shuttle valve can be used in place of the three-way valve 12 and the splitter pump 15 to provide similar treatment. Features. In this configuration, the ultraviolet detector 16 is positioned such that it provides a detector response and generates a component collector 14 signal 61 prior to generation of the signal 31 from the evaporative light scattering detector 13. For example, starting with (i) a single detector response from a single sensor, or (ii) n detector responses from n sensors and a signal where n is greater than one). The UV detector 16 is also positioned such that -36-201022666 enables it to provide a detector response and generate a signal for at least one of a shuttle valve and an evaporative light scattering detector 13 (e.g., initiation) (i) a single detector response from a single sensor, or (ii) a signal from n detectors of n sensors and wherein n is greater than 1) to actuate or deactivate The shuttle valve and/or the evaporative light scattering detector 13 are activated. Although systems 60, 80, and 90 refer to evaporative light scattering detectors and ultraviolet light as detectors, any destructive detector such as an evaporative particle detector can still be used as an evaporative light scattering detector, and Any non-destructive detector can be used to take the Ludai UV detector. In other exemplary embodiments, the liquid chromatography system of the present invention may comprise a non-destructive system comprising two or more non-destructive detectors (eg, one or more optical absorbance detectors, Such as the above-mentioned ultraviolet detectors, and there is no destructive detector (such as a mass spectrometer) in the system. In an exemplary embodiment, 'the liquid chromatography system includes two optical absorbance detectors such as an ultraviolet detector, and the φ step of analyzing the same method includes: using two or more detectors' While observing at two or more specific wavelengths; and reacting (i) a first detector response changes at one of the first wavelengths' (ii) a second detector reacts in a second A change in one of the wavelengths, or (iii) a change in the combination of the first detector reaction and the expression of the second detector reaction - collects a new sample component. In these embodiments, the first wavelength can be substantially the same or different than the second wavelength. In an embodiment using two or more light-detecting detectors such as two or more ultraviolet detectors, the optical absorption detector can be used in a given liquid chromatography system. Internal positioning to provide one or more system advantages. The two or more optical light-absorbing detectors can be positioned in a parallel relationship with each other such that each detector arrives at approximately the same time, and the two or more optically-absorbing detectors can be large The signals are generated and transmitted at the same time (ie, from the first detector and the second detector) to a component collector. In yet another embodiment, a non-destructive use may be used alone or in combination with a destructive detector such as 'evaporation particle detector EPD, mass spectrometer, spectrometer, emission spectroscopy, nuclear magnetic resonance (NMR), etc.) Detector (for example, refractive index RI detector, UV detector, etc.). For example, a destructive detector such as a mass spectrometer detector can allow simultaneous detection of component peaks and chemical entities associated with the peaks. This will allow immediate determination of the ingredients containing the target compound. When other detection techniques are used, it is necessary to carry out separation determination based on, for example, spectrophotometry, mass spectrometry, emission spectroscopy, nuclear magnetic resonance, etc., on which component contains the target compound. If two or more chemical individuals are simultaneously eluted from a fast cartridge (ie, have the same residence time), then certain detectors are used (ie, detection of differences between the chemical entities cannot be identified) When the detectors are unable to determine the chemical composition, the system will deposit the same in the same vial. In an exemplary embodiment in which a mass spectrometer detector is used as the destructive detector, all of the compounds eluted simultaneously can be identified. This will eliminate the need for purity after separation.

在任一上述液相層析系統中,將譬如至少一紫外線UV -38- 201022666 偵檢器等至少一偵檢器,定位於譬如至少一其他紫外線uv 偵檢器或一蒸發光散射偵檢器等至少一其他偵檢器下游 (譬如,串接)者,係屬較優。在此一實施例中,可使用一 第一偵檢器中之一第一偵檢器反應,來產生及傳送一信號 到(1)分流泵、(2) —梭閥、(3)—第二偵檢器、及(4)—三通 閥至少其中之一。例如,可使用一第一偵檢器中之一第一 偵檢器反應,來產生及傳送一信號到一分流泵或一梭閥, 以(i)致動該分流泵或該梭閥、(ii)解除致動該分流泵或該梭 參 閥、(iii)改變該分流泵或該梭閥之一個或更多流動或壓力 設定、或著(iv)該⑴至(iii)之任何組合。適當之流動及壓力 設定包含、但不限於以上描述之流動及壓力設定。典型地, 該信號係呈譬如一電氣信號、一氣動信號、一數位信號、 或一無線信號型式。 在某些實施例中,可將多重偵檢器(即,二個或更多偵 檢器)定位成,使每一偵檢器皆能夠與該系統中其他偵檢器 φ 獨立無關地傳送一信號至(1) 一分流泵、(2) —梭閥、(3)另一 偵檢器、(4) —三通閥至少其中之一。例如,可將多重光學 吸光偵檢器(譬如,紫外線偵檢器)定位於一給定系統內, 以提供獨立無關之複數個信號至一梭閥,致使該梭閥可提 供主動地控制之流體取樣至譬如一蒸發光散射偵檢器等另 一偵檢器。 在其他實施例中’可使用一第一偵檢器中之一第一偵 檢器反應來產生及傳送一信號至一第二偵檢器,以(i)致動 -39- 201022666 該第二偵檢器、(ii)在相似於該第一偵檢器中使用 波長的一波長下,致動該第二偵檢器、(iii)在不 一偵檢器使用之第一波長的一波長下,致動該 器、(iv)解除致動該第二偵檢器、(v)改變該第二 某些其他設定(譬如,該第二偵檢器觀察到之波長 該⑴至(V)之任何組合。 在又其他實施例中,可使用一第一偵檢器中 偵檢器反應來產生及傳送一信號至一三通閥,以 ❹ 閥、或(ii)關閉一閥,來起動或停止通過該液相層 一部分的流體。如上所述者,典型地,該信號係 電氣信號、一氣動信號、一數位信號、或一無線f| C、由一偵檢器反應生成一信號 本發明之方法可尙包括由一個或更多偵檢器 一信號之步驟。在譬如第1圖所顯示之例示性液 統10等某些實施例中,一單一偵檢器可偵檢一樣 φ 之存在,及根據一流體流束內之一樣本組成物的 度爲基礎,來產生一偵檢器反應。在譬如第6圖 例示性液相層析系統50等其他實施例中,可使用 多偵檢器來偵檢一個或更多樣本組成物之存在, 流體流束內之一個或更多樣本組成物的存在及 礎’來產生二個或更多偵檢器反應。 如上所述,一給定偵檢器係提供一個或更多 應’可用於生成及傳送一信號至此中所述之一液 之一第一 同於該第 第二偵檢 偵檢器之 )、或(vi) 之一第一 (i)開啓一 析系統之 呈譬如一 f號型式。 反應生成 相層析系 本組成物 存在及濃 所顯示之 二個或更 及根據一 濃度爲基 偵檢器反 相層析系 -40- 201022666 統內的一個或更多組件(譬如,一成分收集器、另一偵檢 器、一分流泵、一梭閥、或一三通閥)。典型地,一給定偵 檢器反應中之一變化,可觸發一信號之生成及傳送。可觸 發一信號之生成及傳送至一個或更多組件之一給定偵檢器 反應中的變化包含、伹不限於一偵檢器反應値中之一變 化、到達或超過一臨界偵檢器反應値、該偵檢器反應値經 歷一段時間之一斜率、該偵檢器反應値經歷一段時間之一 臨界斜率、該偵檢器反應値經歷一段時間之一斜率中的一 變化、該偵檢器反應値經歷一段時間之一斜率的一臨界變 化、或其任何組合。 在某一例示性實施例中,本發明之方法包括由至少一 偵檢器生成一偵檢器信號之步驟,該偵檢器信號之生成係 反應 u)—偵檢器反應以時間爲函數之斜率(即,一偵檢器 反應之一階導數),(u)該偵檢器反應以時間爲函數之斜率 的一變化(即,該偵檢器反應之二階導數),(iii)可任選地, φ —臨界偵檢器反應値,或(iv)該⑴至(iii)之任何組合,而符 合期望地包括至少(i)或至少(ii)。在例示性實施例中,可使 用該偵檢器反應之表現形式、明確地係該偵檢器反應經歷 一段時間之一階及/或二階導數(即,分別爲斜率、與斜率 之變化),來識別一物質。尤其,一電腦程式可分析偵檢器 反應値之時間序列,且量測其變化率(即,一階導數)、及 變化率之比率(即,二次導數)。當一階導數與二階導數等 二者皆增加時,即開始偵檢到一物質。相似地,當一階導 -41 - 201022666 數與二階導數等二者皆減小時,即停止偵檢該物質。 現實之偵檢器値典型地充滿雜訊(譬如,呈鋸齒狀), 因此期望運用經歷一段時間之低通數値濾波(譬如,平滑 化)。結果,由至少一偵檢器生成一偵檢器信號之步驟依符 合期望地尙包括對(i)經歷一段時間之斜率資料,(Π)經歷一 段時間之斜率資料變化,(iii)可任選地,一臨界偵檢器反 應値,或(iv)該⑴至(iii)之任何組合,進行低通數値濾波, 以區分(i)經歷一段時間之斜率資料,(ii)經歷一段時間之斜 m 率資料變化,(iii)可任選地,一臨界偵檢器反應値,或(iv) 該⑴至(iii)之任何組合中之實際變化與該偵檢器反應中可 能的雜訊。在期望之實施例中,可運用一有限脈衝反應(FIR) 濾波器或一無限脈衝反應(IIR)濾波器來實施經歷一段時間 之資料低通數値濾波(譬如,或許僅爲數個樣本之一平 均)。典型地,決策演算法係運用一段時間內少量的連串成 功,來確認其爲一真確偵檢器反應/信號,而非雜訊。 φ 在其他實施例中,分析一樣本之方法可包括生成一組 合信號,且該信號包括有來自每一偵檢器之一偵檢反應組 成部,及反應該組合信號之一變化來收集一新樣本成分。 在這些實施例中,生成一組合信號之步驟可包括數學地使 以下具有相關性⑴一偵檢器反應値,(ii)一給定偵檢器反應 以時間爲函數之斜率(即,一給定偵檢器反應之一階導 數),(iii)該給定偵檢器反應以時間爲函數之斜率的一變化 (即,該給定偵檢器反應之二階導數),或(iv)來自每一偵檢 -42- 201022666 器(即,二個或更多偵檢器中之每一個)之(ii)至(iii)的任何 組合。例如,在某些實施例中,該組合信號可包括(i)每一 偵檢器(即,二個或更多偵檢器中之每一個)在一給定時間 下的偵檢器反應値乘積,(Π)該等偵檢器反應之一階導數在 一給定時間下的乘積,(iii)該等偵檢器反應之二階導數在 —給定時間下的乘積,或(iv)該⑴至(iii)之任何組合。 在其中使用了 一組合信號之其他實施例中,生成一組 合信號之步驟可包括數學地使以下具有相關性(i)一偵檢器 反應値,(ii)—給定偵檢器反應以時間爲函數之斜率(即, 一給定偵檢器反應之一階導數),(iii)該給定偵檢器反應以 時間爲函數之斜率的一變化(即,該給定偵檢器反應之二階 導數),或(iv)來自一偵檢器內之單獨每一感測器(即,以η 個特定波長觀察一樣本之η個感測器)、或存在於該系統中 之任何其他偵檢器反應的組合等⑴至(iii)的任何組合。例 如,在某些實施例中,該組合信號可包括(i)在一給定時間 φ 下,一偵檢器內之每一感測器(即,以η個特定波長觀察一 樣本之η個感測器)的偵檢器反應値、及來自其他偵檢器(譬 如,來自與一紫外線偵檢器結合使用之一蒸發光散射偵檢 器)的任何附加偵檢器反應値之乘積,(ii)在一給定時間 下,一偵檢器內之每一感測器(即,以η個特定波長觀察一 樣本之η個感測器)之偵檢器反應、及來自其他偵檢器之任 何附加偵檢器反應的一階導數乘積,(iii)在一給定時間 下,一偵檢器內之每一感測器(即,以η個特定波長觀察一 -43- 201022666 樣本之η個感測器)之偵檢器反應、及來自其他偵檢器之任 何附加偵檢器反應的二階導數乘積,或(iv)該⑴至(iii)之任 何組合。 D、收集一個或更多樣本成分 本發明之方法尙包括使用第1圖至第3A圖、及第4圖 至第9圖中所顯示之例示性成分收集器14等一成分收集 器,反應來自一給定液相層析系統中之至少一偵檢器的一 I 個或更多信號,收集一個或更多樣本成分者。例如,在分 別顯示於第1圖、第2圖、及第3A圖中之例示性液相層析 系統10、20、30中,分析一樣本之方法可尙包括,反應來 自第一偵檢器13之一個或更多信號來收集一個或更多樣 本成分的步驟。在分別顯示於第4圖、第5圖、及第6圖 中之例示性液相層析系統40、50、60中,分析一樣本之方 法可尙包括,反應來自第一偵檢器13 (或第一偵檢器131)、 第二偵檢器16(或第二偵檢器161)、或著第一與第二偵檢器 Φ 13與16二者(或第一與第二偵檢器131與161二者)之一個 或更多信號來收集一個或更多樣本成分的步驟。 在本發明之某些實施例中,該成分收集器係作動式地 調整成適應於識別、接收、及處理來自至少一偵檢器之一 個或更多信號,且根據該一個或更多信號爲基礎,收集一 個或更多樣本成分。在其他實施例中,可運用附加的電腦 或微處理設備來處理,來自至少一偵檢器之一個或更多信 號,及隨後提供該成分收集器一可識別之信號,以指示該 -44 - 201022666 成分收集器根據來自該附加電腦或微理設備之一個或更多 信號爲基礎,收集一個或更多樣本成分。 如上所述者,系統組件可定位於一給定液相層析系統 內,以提供一個或更多系統特性。例如,至少一偵檢器可 定位於一給定液相層析系統內,以使(i)對一給定偵檢器反 應之偵檢、與(ii)根據由該偵檢器反應所生成之一信號爲基 礎來收集一樣本成分之步驟之間的任何時間延遲最小化。 在本發明之例示性實施例中,該液相層析系統係依符合期 馨 望地顯現出一給定偵檢器信號到該成分收集器的一最大時 間延遲(即,(i)對一給定偵檢器反應之偵檢、與(ii)根據由 該偵檢器反應所生成之一信號爲基礎來收集一樣本成分之 步驟之間的時間延遲)小於大約2 · 0秒(或小於大約1.5秒、 或小於大約1.0秒、或小於大約0.5秒)。 在運用包括有η個感測器之二個或更多偵檢器、或至 少一偵檢器的本發明例示性實施例中(如上所述者),該液 φ 相層析系統係依符合期望地顯現出來自任何偵檢器之任何 偵檢器信號到該成分收集器的一最大時間延遲(即,(i)對一 給定偵檢器反應之偵檢、與(ii)根據由該偵檢器反應所生成 之一信號(譬如,單一或組合信號)爲基礎來收集一樣本成 分之步驟間的時間延遲)小於大約2.0秒(或小於大約1.5 秒、或小於大約1 · 0秒、或小於大約0 · 5秒)》 E、樣本(複數個)組成物分離步驟 本發明之方法係運用一液相層析(LC)步驟,以在一給 -45- 201022666 定樣本內分離出化合物。根據特殊樣本,可使用各種LC 管柱、移動相、及其他處理步驟條件(譬如,進給率、梯度 等)。 本發明中可使用數個LC管柱。一般而言,本發明中可 使用任何聚合物或無機基正相、逆相、離子交換、親和力、 疏水交互作用、親水交互作用、混合式、及尺寸排斥管柱。 例示性的商業可取得管柱包含、但不限於由Grace Davison Discovery Sciences 取得商標名爲 VYDAC® 、 φ GRACERESOLV™、DAVISIL®、ALLTIMA™、VISION™、 GRACEPURE™、EVEREST®、及 DENALI®之管柱,以及由 其他類似公司取得者。 本發明可使用數個移動相組成物。適當的移動相組成 物包含、但不限於乙氰、二氯甲烷、乙酸乙酯、庚烷、丙 酮、乙醚、四氫呋喃、氯仿、已烷、甲醇、異丙醇、水、 乙醇、緩衝劑、及其組合。 φ F、使用者介面步驟 本發明中分析一樣本之方法可尙包括一個或更多步 驟,其中一操作者或使用者係與一液相層析系統之一個或 更多系統組件連繫。例如,該等分析一樣本之方法可包括 一個或更多步驟:輸入一樣本至該液相層析系統中以作爲 測試用;調整該系統內一個或更多組件之一個或更多設定 (譬如,流動或壓力設定、波長等);以程式規劃至少一偵 檢器,使其根據考慮了來自一個或更多感測器及/或偵檢器 -46- 201022666 之一個或更多偵檢器反應的一期望之數學演算法爲基礎, 來生成一信號;以程式規劃一個或更多系統組件(除一偵檢 器以外),使其根據考慮了一個或更多偵檢器反應之一期望 之數學演算法爲基礎,來生成一信號;以程式規劃一成分 收集器,以識別來自至少一偵檢器之一信號(譬如,一單一 或組合信號),且根據一接收到之信號爲基礎來收集一個或 更多樣本成分;以程式規劃一個或更多系統組件(除一成分 收集器以外),以識別來自至少一偵檢器之一外來進入信 ❹ 號,將該外來進入信號轉換成一成分收集器可識別且可處 理之一信號,使得該成分收集器能夠根據來自該一個或更 多系統組件之輸入爲基礎,收集一個或更多樣本成分;及 在一期望之時間、或反應該液相層析系統內之某些其他活 動(譬如,顯示出提供該操作者或使用者之一偵檢器反 應),來致動或解除致動一個或更多系統組件(譬如,一三 通閥閥、一分流栗、一梭閥、或一偵檢器)。 . II、分析樣本用設備 本發明亦針對一種能夠分析一樣本、或能夠促成藉使 用一個或更多上述方法步驟而達成之一樣本分析的設備及 設備組件。 如上所述者,在本發明之某些例示性實施例中,一分 析一樣本用設備可包括(i) —層析管柱;(ii) 一三通閥’具有 一第一進口,一第一出口,及一第二出口;(iii)一成分收 集器’與該三通閥之該第一出口以流體連通;(iv)-第一偵 -47- 201022666 檢器,與該三通閥之該第二出口以流體連通;及(V)—分流 栗,定位成與該三通閥之該第二出口及該第一偵檢器以流 體連通,且其中該分流泵係作動式地調整成適應於主動地 控制流動至該第一偵檢器之流體者。在本發明之其他例示 性實施例中,可使用一梭閥取代一三通閥/分流泵組合物, 來主動地控制流動至該第一偵檢器之流體》 儘管第1圖至第9圖中未顯示出,然任一上述設備(譬 如,例示性液相層析系統10至90)、或設備組件可尙包括 ❹ 系統硬體,其允許(i)識別一偵檢器反應値、或一偵檢器反 應値中之一變化,(ii)由該偵檢器反應値、或該偵檢器反應 値中之變化生成一信號,(iii)將該信號傳送至一個或更多 系統組件,(iv)識別一接收組件所生成之一信號,(v)處理 該接收組件內之該經識別信號,及(vi)反應該經識別信號, 啓始該接收組件之一處理步驟。 在某一實施例中,該設備(譬如例示性液相層析系統10 φ 至90)、或一給定設備組件可尙包括系統硬體,其允許一第 一偵檢器傳送一致動信號至一分流泵或一梭閥,以(i)致動 該分流栗或梭閥,(ii)解除致動該分流泵或梭閥,(iii)改變 該分流泵或縮閥之二·個或更多流動或壓力設定’或(iv)該(i) 至(iii)之任何組合。適當之流動與壓力設定可包含、但不 限於⑴一閥位置,(ii)分流泵或梭閥壓力,(iii)提供至一閥 之氣壓,或(iv)該⑴至(iii)之任何組合。 在某些實施例中,一分流泵可定位於一三通閥與一第 -48- 201022666 一偵檢器之間(請參閱譬如第1圖中,分流泵15定位於三 通閥12與第一偵檢器13之間)。在其他實施例中,一第一 偵檢器可定位於一三通閥與分流泵之間(請參閱譬如第2圖 中,第一偵檢器13定位於三通閥12與分流泵15之間)。 在其他例示性實施例中,本發明之設備包括(i)層析管 柱;(ii)二個或更多偵檢器;及(iii)一成分收集器,與該二 個或更多偵檢器以流體連通,且其中該成分收集器係作動 式地調整成適應於,反應來自該二個或更多偵檢器之一個 馨 或更多偵檢器信號,收集一個或更多樣本成分。在某些實 施例中,該二個或更多偵檢器包括二個或更多非破壞性偵 檢器(譬如,二個或更多紫外線偵檢器),而系統中無任何 破壞性偵檢器(譬如,質譜儀)。 當存有二個或更多偵檢器時,可使用一分流泵或梭 閥,以在一第一偵檢器與一第二偵檢器之間分離出一體積 量流體。在其他實施例中,可使用一分流泵或梭閥,以反 φ 應來自某一偵檢器之一偵檢器反應,來起動或停止流動至 另一偵檢器之流體。此外,可在一給定系統中使用多重分 流栗及/或梭閥,以主動地控制流動至二個或更多偵檢器之 流體。 如上所述者,該設備可尙包括系統硬體,其允許由一 個或更多偵檢器反應生成一偵檢器信號。在某一例示性實 施例中,該設備包括系統硬體,其允許生成一偵檢器信號, 該偵檢器信號之生成係反應(i)一偵檢器反應以時間爲函數 -49- 201022666 之斜率(g卩,一偵檢器反應之一階導數),(ii)該偵檢器反應 斜率以時間爲函數之一變化(即,該偵檢器反應之二階導 數)’(iii)可任選地,一臨界偵檢器反應値,或(iv)該⑴至(iii) 之任何組合’而符合期望地包括至少(i)或至少(ii)。該系統 硬體依符合期望地尙包括低通數値濾波能力,在經歷一段 時間下,對⑴斜率資料,(ii)斜率資料之變化,(iii)可任選 地,一臨界偵檢器反應値,或(iv)該⑴至(iii)之任何組合濾 波,以區分一給定偵檢器反應中,⑴斜率資料,(ii)斜率資 料之變化,(iii)可任選地,一臨界偵檢器反應値,或(iv)該 (i)至(iii)之任何組合等中的實際變化,與一給定偵檢器反 應中之可能的雜訊。 在多重偵檢器系統中,系統硬體亦可用於允許生成一 組合信號,該組合信號包括來自每一偵檢器之一偵檢反應 組成部、以及來自一給定偵檢器內多重感測器之複數個偵 檢反應組成部。在這些實施例中,該系統硬體係作動式地 φ 調整成適應於,傳送一命令/信號至一成分收集器,以指示 該成分收集器反應該組合中之一變化,收集一新樣本成 分。該組合信號可包括數學地相關對比(i) 一偵檢器反應 値,(ii)—給定偵檢器反應以時間爲函數之斜率(即,一給 定偵檢器反應之一階導數),(iii)該給定偵檢器反應以時間 爲函數之斜率的一變化(即,該給定偵檢器反應之二階導 數),或(iv)來自每一偵檢器之⑴至(iii)的任何組合。例如, 該組合信號可包括(i)在一給定時間下,每一偵檢器之偵檢 -50- 201022666 器反應値的乘積,(π)在一給定時間下,該等偵檢器反應之 一階導數的乘積,(in)在一給定時間下,該等偵檢器反應 之二階導數的乘積,或(iv)該⑴至(iii)之任何組合。 在某一期望之架構中,該分析一樣本用設備包括至少 一偵檢器,作動式地調整成適應於以二個或更多特定光學 波長(譬如,在紫外線頻譜內者)來觀察一樣本,及系統硬 體,允許一成分收集器反應(i)在一第一波長下之一偵檢器 反應變化,(ii)在一第二波長下之一偵檢器反應變化,或(iii) 參 該等第一及第二波長下之偵檢器反應所表達之一組合反應 的一變化,收集一新樣本。每一偵檢器可在(複數個)相同 波長、不同波長、或多重波長下作動。又,每一偵檢器可 呈一相互並聯關係、相互串聯、或爲並聯與串聯偵檢器之 某些組合。 如上所述者,在某一例示性實施例中,該設備可包括 一單一偵檢器,該偵檢器包括η個感測器,作動式地調整 〇 成適應於以橫跨一部份或整個紫外線吸光頻譜(或使用某 些其他型態偵檢器時之吸光頻譜的任何其他部份)之η個特 定光學波長來觀察一樣本,及系統硬體,允許一成分收集 器反應(i)在η個特定光學波長下,η個偵檢器反應中任何 一個的一變化,或(ii)由η個偵檢器反應所表達之一組合反 應中的一變化,收集一新樣本成分。 當設置一分流泵或梭閥而用於主動地控制流動到至少 一偵檢器之流體時,該分析一樣本用設備可尙包括系統硬 -51- 201022666 體,其允許生成一致動信號,提供該分流泵或梭閥,以(i) 致動該分流泵或梭閥,(ϋ)解除致動該分流泵或梭閥,(in) 改變該分流泵或梭閥之一個或更多流動或壓力設定,或(iv) 該⑴至(iii)之任何組合。該致動信號之生成可譬如藉由一 系統操作者、或如一偵檢器(即,該致動信號係藉該偵檢器 反應該偵檢器之一偵檢器反應値、或一偵檢器反應値中之 變化而生成及傳送,如上所述者)等一系統組件達成。 在依據本發明之又更一實施例中,一種使用層析法分 參 析一流體樣本之設備包含一第一流體路徑,自一層析管柱 或卡匣流出;至少一偵檢器,能夠分析該流體樣本;及一 梭閥,可將一整分流體樣本自該第一流體路徑轉運至該(等) 偵檢器,而大致不影響通過該第一流體路徑之流體的流體 特性。由於該第一流體路徑或通道係呈大致線性或筆直地 通過該閥之至少一部分,因此通過該第一流體路徑之流體 流動可大致呈層流。在又一例示性實施例中,通過該第一 Φ 流體路徑之流體壓力可大致保持定値、及/或其大致不增 加。在另一實施例中,該流體之流率在通過該第一流體路 徑時,可大致呈定値。在一替代實施例中,可運用一第二 流體路徑,以將該整分流體樣本自該梭閥運送至該(等)偵 檢器。由於該第二流體路徑或通道係呈大致線性或筆直地 通過該閥之至少一部分,因此通過該第二流體路徑之流體 流動可大致呈層流。在一例示性實施例中,通過該第二流 體路徑之流體壓力可大致爲定値、及/或其大致不增加。在 -52- 201022666 又一實施例中,該流體之流率在通過該第二流體路徑時, 可大致呈定値。 在又更一例示性實施例中,一種使用層析法分析一流 體樣本之設備包含一第一流體路徑,自一層析管柱或卡匣 流出;一第二流體路徑,將該流體樣本運送至能夠分析該 流體樣本之至少一偵檢器;及一梭閥,可將一整分流體樣 本自該第一流體路徑轉運至該第二流體路徑,且同時維持 美 住貫通該梭閥之一連續第二流體路徑。在某一實施例中, φ 當該整分流體樣本自該第一流體路徑移開時,仍可維持住 貫通該梭閥之一連續第一流體路徑。在另一實施例中,當 該整分流體樣本自該第一流體路徑移開且轉運至該第二流 體路徑時,仍可維持住貫通該梭閥之連續第一及第二流體 路徑。 在本發明之例示性實施例中,該分析一樣本用設備尙 包括一成分收集器,其作動式地調整成適應於,反應來自 Φ (i)一第一偵檢器,(ii)一第二偵檢器(或任何數量之附加偵 檢器),或著(iii)該等第一與第二偵檢器二者(或任何數量之 附加偵檢器)之一個或更多偵檢器信號,收集一個或更多樣 本成分。當運用多重偵檢器時,該設備可包括一成分收集 器,作動式地調整成適應於,針對可表達來自每一上述偵 檢器之一個或更多偵檢器反應的一組合信號中之一變化作 反應,收集一新樣本成分。 如上所述者,在某些例示性實施例中,該分析一樣本 -53- 201022666 用設備包括一成分收集器,其作動式地調整成適應於識 別、接收、及處理來自至少一偵檢器之一個或更多信號, 及根據該一個或更多信號爲基礎來收集一個或更多樣本成 分。在其他實施例中,該分析一樣本用設備包括附加的電 腦或微處理設備,其能夠處理來自至少一偵檢器之一個或 更多信號,且將一外來進入信號轉換成可由該成分收集器 識別之一信號。在此後者實施例中,該成分收集器係根據 來自該附加電腦或微處理設備、而非來自該成分收集器中 之信號處理組件的一個或更多信號爲基礎,收集一個或更 多樣本成分。 請注意到,任何的上述例示性液相層析系統皆可包括 任何數量的偵檢器、分流泵、三通閥、及梭閥,該等者可 策略性地置於一給定系統內,以提供一個或更多系統特 性。例如,僅管第6圖中之例示性液相層析系統60未顯示 出,然一附加之偵檢器可定位於管柱11與梭閥151之間、 φ 及/或梭閥151與偵檢器161之間。僅管第7圖中之例示性 液相層析系統70未顯示出,然一附加之偵檢器可定位於管 柱11與梭閥151之間、及/或梭閥151與梭閥171之間、及 /或梭閥171與成分收集器14之間。附加之偵檢器可相似 地分別定位於第8圖與第9圖中所顯示之例示性液相層析 系統80與90內。 , 數個可商業取得之組件,將可用於本發明之設備中, 如下所述者。 -54- 201022666 A、 層析管柱 任何已知的偵檢器,皆可用於本發明之設備中。適當 的可商業取得之偵檢器包含、但不限於由Grace Davison Discovery Sciences(Deerfield,美國伊利諾州)取得商標爲 GRACEPURE™、GRACERESOLV™、VYDAC®、及 DAVISIL® 之層析管柱。 B、 偵檢器 任何已知的偵檢器,皆可用於本發明之設備中。適當 的可商業取得之偵檢器包含、但不限於由 Ocean Optics (Dunedin,美國佛羅里達州)取得商標爲USB 2000™之紫外 線偵檢器;由 Grace Davison Discovery Sciences(Deerfield, 美國伊利諾州)取得商標爲3300 ELSD™之蒸發光散射偵檢 器(ELSD);由 Waters Corporation(Milford,美國麻薩諸塞 州)取得商標爲ZQ™之質譜儀(MS)、由Quant(Blaine,美國 明尼蘇達州)取得商標爲QT-5 00™之一凝聚成核光散射偵 Φ 檢器(CNLSD);由 ESA(Chelmsford,美國麻薩諸塞州)取得 商標爲CORONA CAD™之電暈放電偵檢器(CDD);由Waters Corporation(Milford,美國麻薩諸塞州)取得商標爲2414之 折射率偵檢器(RID);由Laballiance(St. Collect,美國賓夕 法尼亞州)取得商標爲ULTRAFLOR™之螢光偵檢器(fd)。 在某些實施例中,需對一商業取得之偵檢器進行修飾 或以程式規劃,或著需設立一特定偵檢器,以實施本發明 之一個或更多上述方法步驟。 -55- 201022666 c、分流泵 任何已知的分流泵’皆可用於本發明之設備中。適當 的可商業取得之分流泵包含、但不限於由KNF(Trenton ’美 國新澤西州)取得商標爲LIQUID MICRO™之分流泵。 D、 梭閥 任何已知的梭閥,皆可用於本發明之設備中。適當的 可商業取得之梭閥包含、但不限於由Valco(Houston,美國 德州)取得商標爲CHEMINERT™、Rheodyne®之梭閥:由Idex ❹In any of the above liquid chromatography systems, at least one detector, such as at least one ultraviolet UV-38-201022666 detector, is positioned, for example, at least one other ultraviolet uv detector or an evaporative light scattering detector. At least one other detector downstream (for example, in series) is preferred. In this embodiment, one of the first detectors can be used to generate and transmit a signal to (1) the shunt pump, (2) the shuttle valve, (3) - At least one of the second detector and the (4)-three-way valve. For example, one of the first detectors can be used to generate and transmit a signal to a shunt pump or a shuttle valve to (i) actuate the shunt pump or the shuttle valve, ( Ii) deactuating the shunt pump or the shuttle valve, (iii) changing one or more flow or pressure settings of the shunt pump or the shuttle valve, or (iv) any combination of the (1) to (iii). Appropriate flow and pressure settings include, but are not limited to, the flow and pressure settings described above. Typically, the signal is, for example, an electrical signal, a pneumatic signal, a digital signal, or a wireless signal pattern. In some embodiments, multiple detectors (ie, two or more detectors) can be positioned such that each detector can transmit a separate independent of other detectors φ in the system. The signal is at least one of (1) a shunt pump, (2) a shuttle valve, (3) another detector, and (4) a three-way valve. For example, multiple optical absorbance detectors (e.g., ultraviolet detectors) can be positioned in a given system to provide a plurality of independently independent signals to a shuttle valve, such that the shuttle valve provides an actively controlled fluid Sampling to another detector such as an evaporative light scattering detector. In other embodiments, a first detector in a first detector can be used to generate and transmit a signal to a second detector to (i) actuate -39-201022666 the second a detector, (ii) actuating the second detector at a wavelength similar to the wavelength used in the first detector, (iii) a wavelength at a first wavelength used by the detector Actuating the device, (iv) deactivating the second detector, and (v) changing the second certain other settings (eg, the wavelength observed by the second detector (1) to (V) Any other combination. In other embodiments, a detective reaction in a first detector can be used to generate and transmit a signal to a three-way valve to valve the valve, or (ii) close a valve to activate Or stopping the fluid passing through a portion of the liquid phase layer. As described above, typically, the signal is an electrical signal, a pneumatic signal, a digital signal, or a wireless f|C, and a signal is generated by a detector reaction. The method of the invention may include the step of a signal by one or more detectors, as exemplified in Figure 1. In some embodiments, such as liquid system 10, a single detector can detect the presence of the same φ and generate a detector response based on the degree of one of the sample compositions within a fluid stream. In other embodiments, such as exemplary liquid chromatography system 50, a multi-detector can be used to detect the presence of one or more sample constituents, the presence of one or more sample constituents within the fluid stream. And the underlying 'to generate two or more detector responses. As mentioned above, a given detector provides one or more of one of the liquids that should be used to generate and transmit a signal to one of the Together with the second detection and detection device, or (vi) one of the first (i) open the analysis system such as a f-type. Reaction-generated phase chromatography is one or more components (eg, one component) present or concentrated in the presence or concentration of the present composition or more in accordance with a concentration-based detector reverse-phase chromatography system-40-201022666 Collector, another detector, a split pump, a shuttle valve, or a three-way valve). Typically, a change in a given detector response triggers the generation and transmission of a signal. The generation and transmission of a signal can be triggered to one of the one or more components. The change in the response of the given detector includes, is not limited to, a change in one of the detector responses, reaching or exceeding a critical detector response.値, the detector response 値 undergoes a slope for a period of time, the detector response 値 undergoes a critical slope for a period of time, a change in one of the slopes of the detector response, a period of time, the detector The reaction enthalpy undergoes a critical change in slope of one of the periods, or any combination thereof. In an exemplary embodiment, the method of the present invention includes the step of generating a Detector signal by at least one Detector, the generation of the Detector signal is a reaction u) - the Detector response is a function of time The slope (ie, the first derivative of a detector response), (u) a change in the slope of the detector response as a function of time (ie, the second derivative of the detector response), (iii) Alternatively, φ - critical detector reaction 値, or (iv) any combination of (1) to (iii), and desirably includes at least (i) or at least (ii). In an exemplary embodiment, the manifestation of the detector response may be used, explicitly the one-step and/or second derivative of the detector's response over a period of time (ie, the slope, and the change in slope, respectively), To identify a substance. In particular, a computer program can analyze the time series of the detector response and measure the rate of change (i.e., the first derivative) and the rate of change (i.e., the second derivative). When both the first derivative and the second derivative increase, a substance is detected. Similarly, when both the first-order -41 - 201022666 number and the second-order derivative are reduced, the detection of the substance is stopped. Real-world detectives are typically full of noise (for example, jagged), so it is desirable to use low-pass filtering (for example, smoothing) over a period of time. As a result, the step of generating a Detector signal by at least one Detector includes, depending on the desired range, (i) slope data over a period of time, (Π) a slope data change over a period of time, (iii) optional Ground, a critical detector response 値, or (iv) any combination of (1) to (iii), performing low-pass 値 filtering to distinguish between (i) slope data over a period of time, (ii) over a period of time An oblique m-rate data change, (iii) optionally, a critical detector response, or (iv) an actual change in any combination of (1) to (iii) and possible noise in the detector response . In a preferred embodiment, a finite impulse response (FIR) filter or an infinite impulse response (IIR) filter can be used to implement low pass 値 filtering over a period of time (e.g., perhaps only a few samples) An average). Typically, the decision-making algorithm uses a small number of successes over a period of time to confirm that it is a true detector response/signal, rather than noise. φ In other embodiments, the method of analyzing the same may include generating a combined signal, and the signal includes detecting a reaction component from one of each of the detectors, and reacting one of the combined signals to collect a new one. Sample composition. In these embodiments, the step of generating a combined signal can include mathematically having correlation (1) a detector response, (ii) a given detector response as a function of time (ie, a given a one-step derivative of the detector response, (iii) a change in the slope of the given detector response as a function of time (ie, the second derivative of the given detector response), or (iv) from Each detection - 42 - 201022666 (ie, each of two or more detectors) any combination of (ii) to (iii). For example, in some embodiments, the combined signal can include (i) a detector response for each detector (ie, each of two or more detectors) at a given time. Product, (Π) the product of the first derivative of the detector response at a given time, (iii) the product of the second derivative of the detector response at a given time, or (iv) Any combination of (1) to (iii). In other embodiments in which a combined signal is used, the step of generating a combined signal can include mathematically correlating (i) a detector response, (ii) - giving a detector response in time Is the slope of the function (ie, a derivative of a given detector response), (iii) a change in the slope of the given detector response as a function of time (ie, the given detector response) Second derivative), or (iv) each individual sensor from within a detector (ie, n sensors that are observed at n specific wavelengths), or any other stimuli present in the system Combination of detector reactions, etc., any combination of (1) to (iii). For example, in some embodiments, the combined signal can include (i) each sensor within a detector at a given time φ (ie, n as observed at n specific wavelengths) The detector's detector response, and the product of any additional detectors from other detectors (for example, from an evaporative light scattering detector used in conjunction with an ultraviolet detector), Ii) a detector response of each sensor in a detector (ie, n sensors that are observed at n specific wavelengths) at a given time, and from other detectors The first derivative product of any additional detector response, (iii) each sensor within a detector at a given time (ie, one-43-201022666 samples are observed at n specific wavelengths) Detector response of n sensors) and second derivative product of any additional detector responses from other detectors, or (iv) any combination of (1) to (iii). D. Collecting One or More Sample Components The method of the present invention includes the use of a component collector such as the exemplary composition collector 14 shown in Figures 1 to 3A and Figures 4 to 9, the reaction comes from One or more signals of at least one detector in a given liquid chromatography system, one or more sample components are collected. For example, in the exemplary liquid chromatography systems 10, 20, 30 shown in Figures 1, 2, and 3A, respectively, the method of analyzing the same may include, the reaction is from the first detector. The step of one or more signals of 13 to collect one or more sample components. In the exemplary liquid chromatography systems 40, 50, 60 shown in Figures 4, 5, and 6, respectively, the analysis of the same method may include the reaction from the first detector 13 ( Or the first detector 131), the second detector 16 (or the second detector 161), or both the first and second detectors Φ 13 and 16 (or the first and second detections) The step of collecting one or more sample components by one or more signals of both 131 and 161. In some embodiments of the invention, the component collector is operatively adapted to identify, receive, and process one or more signals from the at least one detector, and based on the one or more signals Foundation, collecting one or more sample components. In other embodiments, an additional computer or microprocessor device can be utilized to process one or more signals from at least one detector, and then provide a identifiable signal from the component collector to indicate the -44 - 201022666 The ingredient collector collects one or more sample components based on one or more signals from the additional computer or micro-device. As noted above, system components can be positioned within a given liquid chromatography system to provide one or more system characteristics. For example, at least one detector can be positioned within a given liquid chromatography system such that (i) detection of a given detector is detected, and (ii) generation by reaction by the detector One of the signal-based collections minimizes any time delay between steps of this component. In an exemplary embodiment of the invention, the liquid chromatography system exhibits a maximum time delay for a given detector signal to the component collector (ie, (i) to one The time delay between the detection of a given detector response and (ii) the step of collecting the same component based on a signal generated by the reaction of the detector is less than about 2 · 0 seconds (or less than About 1.5 seconds, or less than about 1.0 seconds, or less than about 0.5 seconds). In an exemplary embodiment of the invention (as described above) employing two or more detectors including n sensors, or at least one detector, the liquid φ phase chromatography system is compliant Desirably exhibiting a maximum time delay from any detector signal from any of the detectors to the component collector (ie, (i) detection of a given detector, and (ii) The time delay between the steps of collecting the same component based on one of the signals generated by the detector reaction (eg, single or combined signal) is less than about 2.0 seconds (or less than about 1.5 seconds, or less than about 1.0 second), Or less than about 0 · 5 seconds) E, sample (plural) composition separation step The method of the present invention uses a liquid chromatography (LC) step to separate the compound in a sample of -45-201022666 . Depending on the particular sample, various LC columns, mobile phases, and other processing step conditions (eg, feedrate, gradient, etc.) can be used. Several LC columns can be used in the present invention. In general, any polymer or inorganic based normal phase, reverse phase, ion exchange, affinity, hydrophobic interaction, hydrophilic interaction, hybrid, and size exclusion column can be used in the present invention. Exemplary commercially available columns include, but are not limited to, those obtained by Grace Davison Discovery Sciences under the trade names VYDAC®, φ GRACERESOLVTM, DAVISIL®, ALLTIMATM, VISIONTM, GRACEPURETM, EVEREST®, and DENALI® , as well as those obtained by other similar companies. Several mobile phase compositions can be used in the present invention. Suitable mobile phase compositions include, but are not limited to, acetonitrile, dichloromethane, ethyl acetate, heptane, acetone, diethyl ether, tetrahydrofuran, chloroform, hexane, methanol, isopropanol, water, ethanol, buffers, and Its combination. φ F, User Interface Steps The method of the present invention can include one or more steps in which one operator or user is associated with one or more system components of a liquid chromatography system. For example, the methods of the analysis may include one or more steps: inputting the same to the liquid chromatography system for testing; adjusting one or more settings of one or more components within the system (eg, , flow or pressure setting, wavelength, etc.); program at least one detector to take into account one or more detectors from one or more sensors and/or detectors -46- 201022666 Based on a desired mathematical algorithm of the reaction, to generate a signal; to program one or more system components (other than a detector) to make it based on one or more of the detector responses considered Based on a mathematical algorithm to generate a signal; program a component collector to identify a signal from at least one of the detectors (eg, a single or combined signal) and based on a received signal To collect one or more sample components; program one or more system components (other than a component collector) to identify an incoming incoming signal from one of the at least one detector Converting the incoming signal into a component collector identifiable and processing one of the signals such that the component collector is capable of collecting one or more sample components based on input from the one or more system components; A desired time, or reaction to some other activity in the liquid chromatography system (for example, showing that the operator or user is one of the detectors) to actuate or deactivate one or more System components (for example, a three-way valve, a split runner, a shuttle valve, or a detector). II. Apparatus for analyzing samples The present invention is also directed to an apparatus and apparatus component capable of analyzing the same, or capable of facilitating one sample analysis by one or more of the above method steps. As described above, in some exemplary embodiments of the present invention, an analytically-used device may include (i) a chromatography column; (ii) a three-way valve having a first inlet, a first An outlet, and a second outlet; (iii) a component collector 'in fluid communication with the first outlet of the three-way valve; (iv) - a first detector - 47 - 201022666 detector, and the three-way valve The second outlet is in fluid communication; and (V)-dividing runners are positioned in fluid communication with the second outlet of the three-way valve and the first detector, and wherein the split pump is operatively adjusted Adapted to actively controlling the flow of fluid to the first detector. In other exemplary embodiments of the invention, a shuttle valve may be used in place of a three-way valve/shunt pump composition to actively control fluid flow to the first detector. Despite Figures 1 through 9 It is not shown that any of the above devices (e.g., exemplary liquid chromatography systems 10 to 90), or device components, may include a system hardware that allows (i) to identify a detector reaction, or a change in one of the detector responses, (ii) generating a signal from the detector response, or a change in the detector response, (iii) transmitting the signal to one or more system components And (iv) identifying a signal generated by a receiving component, (v) processing the identified signal within the receiving component, and (vi) reacting the identified signal to initiate a processing step of the receiving component. In an embodiment, the apparatus (such as the exemplary liquid chromatography system 10 φ to 90), or a given device component, may include a system hardware that allows a first detector to transmit an responsive signal to a split pump or a shuttle valve to (i) actuate the split runner or shuttle valve, (ii) deactivate the splitter or shuttle valve, (iii) change the splitter or reducer or two or more Multiple flow or pressure settings 'or (iv) any combination of (i) to (iii). Suitable flow and pressure settings may include, but are not limited to, (1) a valve position, (ii) a split pump or shuttle valve pressure, (iii) a pressure supplied to a valve, or (iv) any combination of (1) to (iii) . In some embodiments, a split pump can be positioned between a three-way valve and a #48-201022666 detector (see, for example, Figure 1, the split pump 15 is positioned at the three-way valve 12 and Between a detector 13). In other embodiments, a first detector can be positioned between a three-way valve and a split pump (see, for example, FIG. 2, the first detector 13 is positioned between the three-way valve 12 and the split pump 15 between). In other exemplary embodiments, the apparatus of the present invention comprises (i) a chromatography column; (ii) two or more detectors; and (iii) a component collector, with the two or more detectors The detector is in fluid communication, and wherein the component collector is operatively adapted to receive one or more detector signals from the two or more detectors to collect one or more sample components . In some embodiments, the two or more detectors include two or more non-destructive detectors (eg, two or more ultraviolet detectors) without any destructive detection in the system Checker (for example, mass spectrometer). When two or more detectors are present, a split pump or shuttle valve can be used to separate a volume of fluid between a first detector and a second detector. In other embodiments, a split pump or shuttle valve may be used to initiate or stop fluid flow to another detector in response to a detector reaction from one of the detectors. In addition, multiple split and/or shuttle valves can be used in a given system to actively control the flow of fluid to two or more detectors. As noted above, the device can include system hardware that allows one detector signal to be generated by one or more detector responses. In an exemplary embodiment, the apparatus includes a system hardware that allows generation of a detector signal, the detector signal generation response (i) a detector response as a function of time -49- 201022666 The slope (g卩, a detector derivative of the detector), (ii) the detector response slope changes as a function of time (ie, the second derivative of the detector response)' (iii) Optionally, a critical detector reaction 値, or (iv) any combination of (1) to (iii) 'and desirably includes at least (i) or at least (ii). The system hardware includes a low pass 値 filtering capability, a period of time, a (1) slope data, (ii) a change in slope data, (iii) optionally, a critical detector response.値, or (iv) any combination of the filters (1) to (iii) to distinguish between a given detector response, (1) slope data, (ii) change in slope data, (iii) optionally, a critical Detector reaction 値, or (iv) actual changes in any combination of (i) to (iii), etc., possible noise in response to a given detector. In a multiple-detector system, the system hardware can also be used to allow for the generation of a combined signal comprising a detection reaction component from one of each detectors and multiple sensing from a given detector. A plurality of detection reaction components of the device. In these embodiments, the system hard system is operatively φ adapted to transmit a command/signal to a component collector to indicate that the component collector reflects a change in the combination to collect a new sample component. The combined signal can include a mathematically correlated comparison (i) a detector response, (ii) - a slope of a given detector response as a function of time (ie, a given derivative of a given detector response) (iii) a change in the slope of the given detector response as a function of time (ie, the second derivative of the given detector response), or (iv) from each detector (1) to (iii) Any combination of ). For example, the combined signal may comprise (i) the product of each detector's detection -50 - 201022666 reaction 値 at a given time, (π) at a given time, the detectors The product of the first derivative of the reaction, (in) the product of the second derivative of the detector response at a given time, or (iv) any combination of (1) to (iii). In a desired architecture, the analysis apparatus includes at least one detector that is operatively adapted to accommodate two or more specific optical wavelengths (e.g., in the ultraviolet spectrum) to observe the same And system hardware that allows a component collector to react (i) one of the detector response changes at a first wavelength, (ii) one of the detector responses at a second wavelength, or (iii) A new sample is collected by a change in the combined reaction expressed by the detector reaction at the first and second wavelengths. Each detector can operate at (multiple) the same wavelength, different wavelengths, or multiple wavelengths. Also, each of the detectors may be in a parallel relationship, in series with each other, or in some combination of parallel and series detectors. As described above, in an exemplary embodiment, the apparatus can include a single detector that includes n sensors that are operatively adjusted to fit across a portion or η specific optical wavelengths of the entire UV absorption spectrum (or any other part of the absorption spectrum when using some other type of detector) to observe the same, and the system hardware, allowing a component collector reaction (i) A new sample component is collected at a particular optical wavelength, a change in any of the n detector responses, or (ii) a change in one of the combined reactions expressed by the n detector responses. When a shunt pump or shuttle valve is provided for actively controlling the flow of fluid to at least one of the detectors, the analysis apparatus may include a system hard-51-201022666 body that allows for the generation of a consistent motion signal. The split pump or shuttle valve to (i) actuate the split pump or shuttle valve, (ϋ) deactivate the split pump or shuttle valve, (in) change one or more of the split or shuttle valve or Pressure setting, or (iv) any combination of (1) to (iii). The actuating signal can be generated by, for example, a system operator or a detector (ie, the actuating signal is reacted by the detector to react to the detector, or a detective A system component is achieved by generating and transmitting a change in the reaction ,, as described above. In still another embodiment of the present invention, an apparatus for separating a fluid sample by chromatography comprises a first fluid path flowing from a chromatography column or a cassette; at least one detector is capable of The fluid sample is analyzed; and a shuttle valve transports an entire fluid sample from the first fluid path to the detector, substantially without affecting fluid characteristics of the fluid passing through the first fluid path. Since the first fluid path or passageway passes through at least a portion of the valve substantially linearly or straightly, fluid flow through the first fluid path can be substantially laminar. In yet another exemplary embodiment, the fluid pressure through the first Φ fluid path may remain substantially constant, and/or it may not increase substantially. In another embodiment, the flow rate of the fluid can be substantially constant as it passes through the first fluid path. In an alternate embodiment, a second fluid path can be utilized to transport the aliquot of the fluid sample from the shuttle valve to the detector. Since the second fluid path or passageway passes through at least a portion of the valve substantially linearly or straightly, the fluid flow through the second fluid path can be substantially laminar. In an exemplary embodiment, the fluid pressure through the second fluid path may be substantially constant, and/or it may not increase substantially. In still another embodiment of -52-201022666, the flow rate of the fluid is substantially constant when passing through the second fluid path. In still another exemplary embodiment, an apparatus for analyzing a fluid sample using chromatography comprises a first fluid path flowing from a chromatography column or cassette; a second fluid path transporting the fluid sample And at least one detector capable of analyzing the fluid sample; and a shuttle valve for transporting an entire fluid sample from the first fluid path to the second fluid path while maintaining one of the shuttle valves A continuous second fluid path. In one embodiment, φ maintains a continuous first fluid path through one of the shuttle valves when the aliquot of the fluid sample is removed from the first fluid path. In another embodiment, the continuous first and second fluid paths through the shuttle valve are maintained while the aliquot of the fluid sample is removed from the first fluid path and transported to the second fluid path. In an exemplary embodiment of the invention, the analysis apparatus comprises a component collector operatively adapted to respond to Φ (i) a first detector, (ii) a first Two detectors (or any number of additional detectors), or (iii) one or more detectors of both the first and second detectors (or any number of additional detectors) Signal, collect one or more sample components. When multiple detectors are employed, the apparatus can include a component collector operatively adapted to be adapted to a combined signal that can express one or more detector responses from each of the detectors A change reacts to collect a new sample component. As noted above, in some exemplary embodiments, the analysis is the same as the apparatus used in the present invention, including a component collector that is operatively adapted to be adapted to receive, receive, and process from at least one detector. One or more signals, and one or more sample components are collected based on the one or more signals. In other embodiments, the analysis-like device includes an additional computer or microprocessor device capable of processing one or more signals from at least one detector and converting an incoming signal into a component collector Identify one of the signals. In the latter embodiment, the component collector collects one or more sample components based on one or more signals from the additional computer or microprocessing device rather than from a signal processing component in the component collector. . It is noted that any of the above exemplary liquid chromatography systems can include any number of detectors, split pumps, three-way valves, and shuttle valves that can be strategically placed in a given system. To provide one or more system features. For example, although the exemplary liquid chromatography system 60 of FIG. 6 is not shown, an additional detector can be positioned between the column 11 and the shuttle valve 151, φ and/or the shuttle valve 151 and the detector. Between detectors 161. Although the exemplary liquid chromatography system 70 of FIG. 7 is not shown, an additional detector can be positioned between the column 11 and the shuttle valve 151, and/or between the shuttle valve 151 and the shuttle valve 171. Between, and/or between the shuttle valve 171 and the component collector 14. Additional detectors can be similarly positioned within the exemplary liquid chromatography systems 80 and 90 shown in Figures 8 and 9, respectively. Several commercially available components will be used in the apparatus of the present invention, as described below. -54- 201022666 A. Chromatographic column Any known detector can be used in the apparatus of the present invention. Suitable commercially available detectors include, but are not limited to, chromatography columns available from Grace Davison Discovery Sciences (Deerfield, Ill., USA) under the trademarks GRACEPURETM, GRACERESOLVTM, VYDAC®, and DAVISIL®. B. Detector Any known detector can be used in the apparatus of the present invention. Suitable commercially available detectors include, but are not limited to, UV detectors licensed by Ocean Optics (Dunedin, Fla., USA) under the trademark USB 2000TM; obtained by Grace Davison Discovery Sciences (Deerfield, Ill.) Evaporative Light Scattering Detector (ELSD) under the trademark 3300 ELSDTM; mass spectrometer (MS) available from Waters Corporation (Milford, MA) under the trademark ZQTM, by Quant (Blaine, Minnesota, USA) Obtained a condensed nucleation light scattering detector (CNLSD) with the trademark QT-5 00TM; Corona Discharge Detector (CDD) with the trademark CORONA CADTM from ESA (Chelmsford, Massachusetts, USA) ); a refractive index detector (RID) with a trademark of 2414 obtained by Waters Corporation (Milford, Massachusetts, USA); a fluorescent detection of ULTRAFLORTM by Laballiance (St. Collect, PA) (fd). In some embodiments, a commercially available detector is modified or programmed, or a particular detector is required to implement one or more of the above method steps of the present invention. -55- 201022666 c. Shunt pump Any known split pump' can be used in the apparatus of the present invention. Suitable commercially available split pumps include, but are not limited to, a split pump available from KNF (Trenton ' New Jersey, USA) under the trademark LIQUID MICROTM. D. Shuttle Valves Any known shuttle valve can be used in the apparatus of the present invention. Suitable commercially available shuttle valves include, but are not limited to, shuttle valves sold by Valco (Houston, Texas) under the trademark CHEMINERTTM, Rheodyne®: by Idex ❹

Corporation取得商標名爲MRA®之梭閥;及此中所述之一 連續流動梭閥。 E、 成分收集器 任何已知的成分收集器,皆可用於本發明之設備中。 適當的可商業取得之成分收集器包含、但不限於由 Gilson(Middleton,美國威斯康辛州)取得商標爲215之成分 收集器。 φ 在某些實施例中,需對一商業取得之成分收集器進行 修飾及/或以程式規劃,或著需設立一特定成分收集器,以 實施本發明之一個或更多上述方法步驟。例如,以作動式 地調整成適應於識別、接收、及處理來自至少一偵檢器之 一個或更多信號,及根據該一個或更多信號爲基礎來收集 一個或更多樣本成分之成分收集器,此時即無法商業地取 得。 III、電腦軟體 -56- 201022666 本發明又針對一種電腦可讀媒體’其上儲存有可實施 一個或更多上述方法步驟之電腦可讀指令。例如’該電腦 可讀媒體上,可儲存有電腦可執行指令’用於:調整該系 統內一個或更多組件之一個或更多設定(譬如’流動設定、 波長等);根據考慮了一個或更多偵檢器反應之一期望的數 學演算法爲基礎,來生成一信號;識別來自至少一偵檢器 之一信號;根據一接收到之信號爲基礎’收集一個或更多 樣本成分;識別來自至少一偵檢器之一外來進入信號,將 該外來進入信號轉換成可由一成分收集器識別與處理之一 信號,使得.該成分收集器能夠根據來自該一個或更多系統 組件之輸入爲基礎,收集一個或更多樣本成分;及在一期 望之時間、或反應該液相層析系統內之某些其他活動(譬 如,一偵檢器反應),來致動或解除致動一個或更多系統組 件(譬如,一三通閥閥、一分流泵、一梭閥、或一偵檢器)。 IV、應用/使用 Φ 可使用上述方法、設備、及電腦軟體,來偵檢各式各 類樣本中是否存有一個或更多化合物。上述方法、設備、 及電腦軟體’可在運用液相層析法之任何工業中發現其適 用性,該工業包含、但不限於石化工業、製藥工業、分析 實驗室等。 範例 可由以下範例進一步闡明本發明,不應將該等範例解 釋爲對本發明範疇加諸限制者。相反地,可清楚地了解到, -57- 201022666 應訴諸熟知此項技藝之人士在閱讀此中之說明後可聯想到 的各種其他實施例、修飾、及其等效者,而不致脫離本發 明之精神、及/或附屬申請專利範圍之範疇。 範例1 在本範例中,可運用快速REVELERIS™系統(可由Grace . Davison Discovery Sciences取得)。將包含有蔗糖及阿斯匹 靈之一4毫升(mL)混合物注入至,安裝於該快速系統中之 -4 公克(g)GRACERES0LV™C18 快速管柱(可由 Grace Davison Discovery Sciences 取得)中。使用 一 ALLTECH® 300 LC型泵,將一50/5 0甲醇/水移動相抽吸通過該系統。將該 管柱流出物導至一 KNF分流泵,而由該分流栗將3 00微升/ 分鐘UL/min)之管柱流出物轉向至一ALLTECH® 3300蒸 發光散射偵檢器。該流出物之剩餘部分將通過一Ocean Optics紫外線偵檢器,而至一 Gilson成分收集器。 蔗糖與阿斯匹靈可在該快速管柱上相互分離。蔗糖與 φ 該阿斯匹靈可由該蒸發光散射偵檢器偵檢到。該紫外線偵 檢器僅可偵檢到阿斯匹靈。該等偵檢器二者可同時對阿斯 匹靈產生反應。該成分收集器可反應來自該紫外線及ELS 偵檢器之一組合信號,將蔗糖與阿斯匹靈沉積於分離之收 集小瓶中。 範例2 在本範例中,可運用快速REVELERIS™系統(可由Grace Davison Discovery Sciences取得)。將包含有鄰苯二甲酸二 -58- 201022666 辛酯及對羥基苯甲酸丁酯之一4毫升(mL)混合物注入至, 安裝於該快速系統中之一4公克(g) GRACERESOLV™ci8快 速管柱(可由 Grace Davison Discovery Sciences 取得)中。使 用一 ALLTECH® 3 00 LC型泵,將一80/20甲醇/水移動相抽 吸通過該系統。將該管柱流出物導至如此中所述之一梭 閥,而由該分流泵將300微升/分鐘(m L/min)之管柱流出物 轉向至一ALLTECH® 3300蒸發光散射偵檢器。該流出之 • 剩餘部分將通過一 Ocean Optics紫外線偵檢器,而至一 ❹Corporation has obtained a shuttle valve under the trade name MRA®; and one of the continuous flow shuttle valves described herein. E. Component Collector Any known ingredient collector can be used in the apparatus of the present invention. Suitable commercially available component collectors include, but are not limited to, a component of the composition of 215 obtained by Gilson (Middleton, Wisconsin, USA). φ In some embodiments, a commercially available component collector is modified and/or programmed, or a specific component collector is required to implement one or more of the above method steps of the present invention. For example, component adjustments that are operatively adapted to identify, receive, and process one or more signals from at least one detector and collect one or more sample components based on the one or more signals This is not commercially available at this time. III. Computer Software -56- 201022666 The present invention is further directed to a computer readable medium having stored thereon computer readable instructions that perform one or more of the above method steps. For example, 'the computer readable medium can be stored with computer executable instructions' for: adjusting one or more settings of one or more components of the system (eg, 'flow settings, wavelengths, etc.); More of the detector response is based on a desired mathematical algorithm to generate a signal; identifying a signal from at least one of the detectors; collecting one or more sample components based on a received signal; identifying An incoming signal from one of the at least one detectors that converts the incoming signal into a signal that can be identified and processed by a component collector such that the component collector can input based on input from the one or more system components Basis, collecting one or more sample components; and actuating or deactivating one or the other at a desired time, or in response to some other activity in the liquid chromatography system (eg, a detector response) More system components (for example, a three-way valve, a split pump, a shuttle valve, or a detector). IV. Application/Use Φ The above methods, equipment, and computer software can be used to detect the presence or absence of one or more compounds in various samples. The above methods, apparatus, and computer software can be found to be useful in any industry employing liquid chromatography, including, but not limited to, the petrochemical industry, the pharmaceutical industry, analytical laboratories, and the like. The invention is further clarified by the following examples, which should not be construed as limiting the scope of the invention. Conversely, it is to be understood that the various other embodiments, modifications, and equivalents thereof that are known to those skilled in the art after reading this description are not to be The spirit of the invention, and/or the scope of the scope of the appended claims. Example 1 In this example, the fast REVELERISTM system (available from Grace. Davison Discovery Sciences) can be used. A 4 ml (mL) mixture containing one of sucrose and aspirin was injected into a -4 g (g) GRACERES0LVTM C18 fast column (available from Grace Davison Discovery Sciences) in the rapid system. A 50/5 methanol/water mobile phase was pumped through the system using an ALLTECH® 300 LC pump. The column effluent is directed to a KNF shunt pump from which the 300 liter/min UL/min column effluent is diverted to an ALLTECH® 3300 evaporative scatter detector. The remainder of the effluent will pass through an Ocean Optics UV detector to a Gilson ingredient collector. Sucrose and aspirin can be separated from each other on the fast column. Sucrose and φ The aspirin can be detected by the evaporative light scattering detector. The UV detector only detects aspirin. Both of these detectors can simultaneously react to aspirin. The component collector reacts with a combined signal from one of the UV and ELS detectors to deposit sucrose and aspirin in separate collection vials. Example 2 In this example, the fast REVELERISTM system (available from Grace Davison Discovery Sciences) is available. Inject 4 ml (mL) mixture containing octyl phthalate di-58- 201022666 octyl ester and butyl parahydroxybenzoate into one of the fast systems, 4 g (g) GRACERESOLVTMci8 fast tube Column (available from Grace Davison Discovery Sciences). An 80/20 methanol/water mobile phase was pumped through the system using an ALLTECH® 3 00 LC pump. The column effluent is directed to one of the shuttle valves described herein, and the 300 liter/minute (m L/min) column effluent is diverted by the split pump to an ALLTECH® 3300 evaporative light scattering detection Device. The outflow of the remaining part will pass through an Ocean Optics UV detector, to the same

Gilson成分收集器。 該二組成物混合物包含有一非載色化合物(不吸收紫 外線者)、及一載色化合物。該非載色化合物先由該快速卡 匣洗提。第11圖描繪出一層析圖,其闡明僅蒸發光散射偵 檢器,即鑑別出樣本中之所有組成物,這可由該層析圖上 之二峰値獲得證明。即使在二波長下,紫外線偵檢器仍未 鑑別出非載色化合物(由蒸發光散射偵檢器鑑別出之第一 〇 峰値者)。僅蒸發光散射偵檢器信號即能夠適洽地控制成分 收集器,來捕獲該二化合物。倘由紫外線偵檢器驅動該成 分收集器(習知快速系統中即爲此情形),則該第一化合物 將認定爲廢棄物或錯誤地沉積於收集器皿中,而無該等成 分包含有期望樣本之訊息。在習知快速儀器中,所有成分 皆將於層析分離後,藉薄層層析(TLC)篩選,以尋找紫外線 偵檢器未能鑑別出之化合物。本範例可展現出,依據本發 明之配備有一蒸發光散射偵檢器的快速儀器,將能夠鑑別 -59- 201022666 且分離載色及非載色化合物二者’且不再需要後分離TLC 篩選。 儘管可藉有限數量之實施例來說明本發明,然並非意 欲以這些特定實施例來限制本發明之範疇,而發明範疇係 於此中說明及主張者。顯而易見地,熟知此項技藝之人士 在檢視此中之例示性實施例後將可明白,進一步之修飾、 等效物、及替代者皆屬可能。除非特別指定,否則範例中、 及說明書其餘部中之所有分部及百分率皆依重量計。又, Φ 說明書或申請專利範圍中所列舉之任何數字範圍,如表達 —特殊組特性、量測單位、條件、物理狀態、或百分率者, 皆意欲藉參考方式逐字而明確地倂入此中,或著爲屬於這 種範圍內之任何數字,這包含任何所列舉範圍內之任何數 字子集。例如,每當揭示具有下限Ri·與一上限Ru之一數 値範圍時,則係明確地揭示爲屬於該範圍內之任何數字 R。尤其,明確地揭示爲該範圍內之以下數字 R: Φ R = RL + k(Ru-RL),其中k爲範圍介於1%至100%且以1%爲遞 增量之一變數,譬如k爲1 %、2%、3%、4%、5%、…50%、 51%、52%...95%、96%、97%、98%、9 9%、或 100%。此外, 亦可明確揭示由任何二R値表達、依以上者計算出之任何 數値範圍。熟知此項技藝之人士由以上說明及隨附圖式將 可發現,除此中顯示及說明者以外的任何發明修飾。意欲 使這種修飾屬於附靥申請專利範圍內。此中引用之所有公 開案皆以參考方式完全倂入本案中。 -60- 201022666 【圖式簡單說明】 第1圖描繪出本發明之一例示性液相層析系統,其包 括一分流泵’來主動地控制流動至一偵檢器之流體; 第2圖描繪出本發明之另一例示性液相層析系統,其 包括一分流泵及一偵檢器; 第3A圖描繪出本發明之一例示性液相層析系統,其包 括一梭閥及一偵檢器; ❹ 第3B圖及第3C圖描繪出適合於本發明中之—例示性 梭閥的作動; 第4圖描繪出本發明之一例示性液相層析系統,其包 括一分流泵及二偵檢器; 第5圖描繪出本發明之一例示性液相層析系統,其包 括二分流泵及二偵檢器; 第6圖描繪出本發明之一例示性液相層析系統,其包 括一梭閥及二偵檢器; 〇 第7圖描繪出本發明之一例示性液相層析系統,其包 括二梭閥及二偵檢器; 第8圖描繪出本發明之一例示性液相層析系統,其包 括一分流泵、一蒸發光散射偵檢器(ELSD)、及一紫外線(UV) 偵檢器; 第9圖描繪出本發明之另一例示性液相層析系統,其 包括一分流泵、一蒸發光散射偵檢器、及一紫外線偵檢器; 第10A圖及第10C圖描繪出適合於本發明中之一例示 -61- 201022666 性梭閥的作動;及 第11圖描繪出經由使用本發明之一例示性層析系統 來分離一具有二組成物之混合物時,所產生之一層析圖。 【主要元件符號.說明】 10 液相層析系統 11 層析管柱 12 三通閥Gilson ingredient collector. The two composition mixture contains a non-ferrous compound (which does not absorb ultraviolet rays), and a coloring compound. The non-coloured compound is first eluted from the flash card. Figure 11 depicts a chromatogram illustrating the evaporative light scattering detector, i.e., identifying all of the constituents in the sample, as evidenced by the two peaks on the chromatogram. Even at the two wavelengths, the UV detector did not identify non-carrier compounds (the first peak identified by the Evaporative Light Scatter Detector). Evaporating the light scattering detector signal only allows the component collector to be properly controlled to capture the two compounds. If the component collector is driven by an ultraviolet detector (as is the case in conventional rapid systems), the first compound will be identified as waste or erroneously deposited in the collection vessel without the inclusion of such ingredients Sample message. In conventional fast instruments, all components are chromatographed and chromatographed by thin layer chromatography (TLC) to find compounds that are not identified by the UV detector. This example demonstrates that a fast instrument equipped with an evaporative light scattering detector in accordance with the present invention will be able to identify -59-201022666 and separate both the color and non-ferrous compounds' and no longer require post-separation TLC screening. While the invention may be described by a limited number of embodiments, it is not intended to limit the scope of the invention, and the scope of the invention is described and claimed. It will be apparent that those skilled in the art will recognize that further modifications, equivalents, and alternatives are possible. All divisions and percentages in the examples, and in the remainder of the specification, are by weight unless otherwise specified. Also, any numerical range recited in the specification or the scope of the patent application, such as expression - special group characteristics, measurement unit, condition, physical state, or percentage, is intended to be entered literally and explicitly by reference. Or any number falling within this range, which includes any subset of numbers within any recited range. For example, whenever a range of the lower limit Ri· and an upper limit Ru is revealed, it is explicitly disclosed as any number R within the range. In particular, it is explicitly disclosed as the following number R in the range: Φ R = RL + k(Ru-RL), where k is a variable ranging from 1% to 100% and incremented by 1%, such as k It is 1%, 2%, 3%, 4%, 5%, ... 50%, 51%, 52%...95%, 96%, 97%, 98%, 99%, or 100%. In addition, any range of numbers calculated by any of the two R 、 and calculated by the above may also be clearly disclosed. Any person skilled in the art will be able to devise various modifications of the invention in addition to those shown and described herein. It is intended that such modifications are within the scope of the patent application. All publications cited herein are incorporated by reference in their entirety. -60- 201022666 [Simultaneous Description of the Drawings] Figure 1 depicts an exemplary liquid chromatography system of the present invention comprising a shunt pump to actively control the flow of fluid to a detector; Figure 2 depicts Another exemplary liquid chromatography system of the present invention includes a shunt pump and a detector; FIG. 3A depicts an exemplary liquid chromatography system of the present invention including a shuttle valve and a detector ❹ 3B and 3C depict the operation of an exemplary shuttle valve suitable for use in the present invention; FIG. 4 depicts an exemplary liquid chromatography system of the present invention including a split pump and Second detector; Figure 5 depicts an exemplary liquid chromatography system of the present invention comprising a two-split pump and a second detector; Figure 6 depicts an exemplary liquid chromatography system of the present invention, It comprises a shuttle valve and a second detector; 〇 Figure 7 depicts an exemplary liquid chromatography system of the present invention comprising a second shuttle valve and a second detector; Figure 8 depicts an illustration of the invention Liquid chromatography system, including a shunt pump, an evaporative light scattering detector (ELSD) And an ultraviolet (UV) detector; FIG. 9 depicts another exemplary liquid chromatography system of the present invention, including a shunt pump, an evaporative light scattering detector, and an ultraviolet detector; 10A and 10C depict the operation of an exemplary -61-201022666 shuttle valve suitable for use in the present invention; and FIG. 11 depicts the separation of a two-component composition using an exemplary chromatography system of the present invention. One of the chromatograms produced when the mixture is mixed. [Main component symbol. Description] 10 Liquid chromatography system 11 Chromatography column 12 3-way valve

13 第一偵檢器 14 成分收集器 15 分流泵 16 第二偵檢器 17 第二分流泵 18 第二三通閥 20 液相層析系統 21 第一入口 22 第一出口 23 第二出口 30 液相層析系統 3 1 第一入口偵檢器)信號 32 第一出口 33 第二出口 40 液相層析系統 50 液相層析系統 -62- 20102266613 first detector 14 component collector 15 split pump 16 second detector 17 second split pump 18 second three-way valve 20 liquid chromatography system 21 first inlet 22 first outlet 23 second outlet 30 liquid Phase tomography system 3 1 first inlet detector) signal 32 first outlet 33 second outlet 40 liquid chromatography system 50 liquid chromatography system -62- 201022666

60 液 相 層 析 系 統 61 (偵檢器)信號 70 液 相 層 析 系 統 80 液 相 層 析 系 統 90 液 相 層 析 系 統 111 層 析 卡 匣 入 Ρ 113 偵 檢 器 出 □ 114 成 分 收 集 器 出 Ρ 115 氣 體 或 液 體 入 □ 116 外 來 進 入 樣 本 整 分 體 凹 坑 1 17 排 出 樣 本 整 分 體 通 道 118 樣 本 整 分 外 來 進 入 樣 本 整分體 119 動 態 本 體 120 通 道 121 凹 坑 旋 轉 路 徑 122 態 本 體 R.3Z. 123 氣 囊 124 成 分 收 集 器 出 口 125 氣 體 或 液 體 入 13 1 第 —* 偵 檢 器 151 梭 閥 152 流 體 供 應 裝 置 161 第 二 偵 檢 器 -63- 201022666 171 梭閥 172 流體供應裝置 3 11 (偵檢器)信號 611 (偵檢器)信號60 liquid chromatography system 61 (detector) signal 70 liquid chromatography system 80 liquid chromatography system 90 liquid chromatography system 111 chromatography card Ρ 113 detector □ 114 component collector Ρ 115 Gas or liquid into □ 116 Externally entering the sample whole body pit 1 17 Discharge sample plough body channel 118 Sample aliquot Exogenous into sample ploid body 119 Dynamic body 120 Channel 121 Pit rotation path 122 State body R.3Z. 123 Airbag 124 Component Collector Outlet 125 Gas or Liquid Into 13 1 -* Detector 151 Shuttle Valve 152 Fluid Supply 161 Second Detector -63 - 201022666 171 Shuttle Valve 172 Fluid Supply 3 11 (Detector ) signal 611 (detector) signal

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Claims (1)

201022666 七、申請專利範圍: 1. 一種分析一樣本之方法’該方法之步驟包括: (a) 由一液相層析系統中之二個或更多偵檢器生成 合信號,該組合信號包括來自每一該等偵檢器之一 反應組成部;及 (b) 反應該組合信號中之一變化,將一新樣本成分 於一成分收集器中。 2. 如申請專利範圍第1項之方法,該生成一組合信號 U)數學地使以下具有相關性:(i)一偵檢器反應値 一給定偵檢器反應以時間爲函數之斜率(即,一給定 器反應之一階導數),(iii)該給定偵檢器反應以時間 數之斜率的一變化(即,該給定偵檢器反應之二階導 或(iv)來自每一該等偵檢器之⑴至(iii)的任何組合。 3. 如申請專利範圍第1項之方法,其中該組合信號包 每一該等偵檢器在一給定時間下之偵檢器反應値乘 (ii)該等偵檢器反應之一階導數在一給定時間下 積,(iii)該等偵檢器反應之二階導數在一給定時間下 積,或(iv)該⑴至(iii)之任何組合》 4. 如申請專利範圍第丨項之方法,其步驟尙包括: (a)使用至少一偵檢器,在二個或更多特定光學波 觀察該樣本,以產生在該二個或更多特定光學波長 二個或更多偵檢器反應;該組合信號包括一偵檢反 成部,其係來自該二個或更多特定光學波長下之該 一組 偵檢 收集 之步 ,(ii) 偵檢 爲函 數), 括⑴ 積, 的乘 的乘 長下 下之 應組 二個 -65- 201022666 或更多偵檢器反應者。 5. 如申請專利範圍第4項之方法,其中該至少—偵檢器觀 察二個或更多特定光學波長者包括至少—紫外線(uv)偵 檢器’且該組合信號包括(i)來自該紫外線偵檢器於該二 個或更多特定光學波長下之該二個或更多偵檢器反應的 一偵檢反應組成部,及(ii)來自一蒸發光散射偵檢器 (ELSD)之一偵檢反應組成部。 6. 如申請專利範圍第1項之方法,其中該組合信號包括⑴ 來自至少一紫外線偵檢器之一偵檢反應組成部,及(ii)來 自至少一蒸發光散射偵檢器(ELSD)之一偵檢反應組成 部。 7. 如申請專利範圍第1項之方法,其尙包括: (a)經由定位成可與至少一偵檢器以流體連通之(i) 一 分流泵、(ii)—梭閥、或著(iii)該⑴與(ii)二者,主動地控 制流動至該液相層析系統中之該至少一偵檢器的流體。 φ 8.如申請專利範圍第1項之方法,其尙包括: (a)經由定位成可與至少一偵檢器以流體連通之一梭 閥,主動地控制流動至該液相層析系統中之該至少一偵 檢器的流體。 9. 如申請專利範圍第8項之方法,其中該至少一偵檢器包 括一蒸發光散射偵檢器(ELSD)。 10. 如申請專利範圍第8項之方法,其尙包括: (a)利用空氣將一樣本整分自該梭閥傳輸至該至少一 -66- 201022666 偵檢器。 11·如申請專利範圍第8項之方法,其中該梭閥係以每10 秒(s)至少1樣本整分之一取樣頻率,將一樣本整分自該 樣本移開,而傳輸至該至少一偵檢器。 12. —種分析一樣本之方法,該方法之步驟包括: (a) 使用至少一偵檢器,而在二個或更多特定波長下觀 察一樣本:及 (b) 反應(i) 一偵檢器反應在一第一波長下之一變化,(ii) 參 —偵檢器反應在一第二波長下之一變化,或(iii)該等偵 檢器反應所表達之一組合反應在該等第一與第二波長下 的一變化,將一新樣本成分收集於一成分收集器中。 13. 如申請專利範圍第12項之方法’其步驟尙包括: (a)反應(i)—偵檢器反應在一第一波長下之一變化, (ii) 一偵檢器反應在—第二波長下之一變化’或(出)該等 偵檢器反應所表達之一組合反應在該等第一與第二波長 φ 下的一變化,將一新樣本成分收集於該成分收集器中。 14. 如申請專利範圍第12項之方法’其步驟尙包括: (a) 使用至少一偵檢器中之η個感測器’在橫跨一吸光 頻譜之一範圍內的η個特定波長下觀察該樣本’其中η 係大於1之一整數;及 (b) 反應⑴來自該η個感測器之η個偵檢器反應中任— 個的一變化,或(丨丨)由該η個偵檢器反應所表達之一組合 反應中的一變化,將一新樣本成分收集於該成分收集器 -67- 201022666 中〇 15. 如申請專利範圍第14項之方法,其中該吸光頻譜之範 圍係一紫外線(UV)範圍。 16. 如申請專利範圍第14項之方法,其中該系統包括—單 一紫外線偵檢器’其單獨包括了 η個感測器、或其可結 合一個或更多附加偵檢器。 17. 如申請專利範圍第14項之方法,其尙包括: φ (a)經由定位成可與至少一偵檢器以流體連通之⑴一 分流泵、(ii)—梭閥、或著(iii)該⑴與(ii)二者,主動地 控制流至該液相層析系統中之該至少一偵檢器的流體。 18. 如申請專利範圍第14項之方法,其尙包括: (a) 經由定位成可與至少一偵檢器以流體連通之一梭 閥,主動地控制流動至該液相層析系統中之該至少一偵 檢器的流體。 19. 一種分析一樣本之方法,該方法之步驟包括: 〇 U)提供一液相層析系統,其包括⑴一層析管柱’(ii) 一成分收集器,及(iii)—第一偵檢器;及 (b) 經由定位成與該第一偵檢器以流體連通之(iv)—分 流泵或一梭閥,主動地控制流動至該第一偵檢器之流體。 20. 如申請專利範圍第19項之方法’該主動地控制流動至 第一偵檢器之流體的步驟包括: U)傳送一致動信號至該分流泵或梭閥,來⑴致動該分 流泵或梭閥,(Π)解除致動該分流泵或梭閥’(111)改變該 -68- 201022666 分流泵或梭閥之一個或更多流動或壓力設定,或(iv)該⑴ 至(iii)之任何組合。 21. 如申請專利範圍第20項之方法,其中該一個或更多流 動或壓力設定包括(i) 一閥位置,(ii)分流泵或梭閥壓 力,(iii)提供至一閥之氣壓,或(iv)該⑴至(iii)之任何組 合。 22. 如申請專利範圍第20項之方法,其中該致動信號包括 A —電氣信號、一氣動信號、一數位信號、或一無線信號。 2 3.如申請專利範圍第19項之方法,其中該主動地控制流 動至第一偵檢器之流體的步驟包括,經由該分流泵將流 體抽吸至該第一偵檢器中者。 24.如申請專利範圍第19項之方法,其中該主動地控制流 動至第一偵檢器之流體的歩驟包括,經由該分流泵將流 體拉拖通過該第一偵檢器者。 2 5.如申請專利範圍第19項之方法,其中該主動地控制流 〇 動至第一偵檢器之流體的步驟包括,經由一梭閥將一個 或更多樣本整分提供至該第一偵檢器者。 26. 如申請專利範圍第19項之方法,其中該液相層析系統 尙包括(v)—第二偵檢器;該主動地控制流動至第一偵檢 器之流體的步驟包括,在該第一偵檢器與該第二偵檢器 之間,將一體積量之流體流動分流者。 27. 如申請專利範圍第19項之方法,其中該液相層析系統 尙包括(v) —第二偵檢器;該方法之步驟尙包括: -69- 201022666 (a)反應該第二偵檢器偵檢出一樣本中之一組成物,傳 送一信號至該分流泵或該梭閥,以指示該分流泵或該梭 閥起始或停止流體流動至該第一偵檢器。 28.如申請專利範圍第19項之方法,其中該液相層析系統 尙包括(v)—第二偵檢器,及(Vi) —第二分流泵或一第二 梭閥;該方法之步驟尙包括: (a)經由該第二分流泵或該第二梭閥,主動地控制流動 至該第二偵檢器之流體。 φ 2 9.如申請專利範圍第19項之方法,其步驟尙包括: (a)反應來自該第一偵檢器之一個或更多信號,收集一 個或更多樣本成分。 3 0.如申請專利範圍第26項之方法,其步驟尙包括: (a)反應來自(i)該第一偵檢器,(ii)該第二偵檢器,或 (iii)該等第一與該第二偵檢器二者之一個或更多偵檢器 信號,收集一個或更多樣本成分。 φ 31.如申請專利範圍第26項之方法,其中該液相層析系統 係包括一個或更多非破壞性偵檢器且無任何破壞性偵檢 器之一非破壞性系統。 32.如申請專利範圍第19項之方法,其步驟尙包括: (a)由至少一偵檢器生成一偵檢器信號,該偵檢器信號 之生成係反應(i) 一偵檢器反應以時間爲函數之斜率 (即,一偵檢器反應之一階導數),(ii)該偵檢器反應以時 間爲函數之斜率的一變化(即,該偵檢器反應之二階導 -70- 201022666 數)’(iii)可任選地’到達或超過一臨界偵檢器反應値, 或(iv)包括至少(i)或至少(iii)之⑴至(iii)之任何組合者。 33·如申請專利範圍第32項之方法,其中該由至少一偵檢 器生成一偵檢器信號之步驟尙包括: (a)針對(i)經歷一段時間之斜率資料,(ii)經歷一段時 間之斜率資料變化,(iii)可任選地,一臨界偵檢器反應 値,或(iv)該⑴至(iii)之任何組合,進行低通數値濾波, 以區分(i)經歷一段時間之斜率資料,(ii)經歷—段時間 之斜率資料變化’(iii)可任選地,—臨界偵檢器反應値, 或(iv)該⑴至(iii)之任何組合中之實際變化與該偵檢器 反應中可能的雜訊。 34.如申請專利範圍第26項之方法,其步驟尙包括: (a) 生成一組合信號,其包括來自每一該等偵檢器之一 偵檢反應組成部;及 (b) 反應該組合信號中之一變化,收集一新樣本成分。 3 5.如申請專利範圍第34項之方法,該生成一組合信號之 步驟包括: (a)數學地使以下具有相關性⑴一偵檢器反應値,(ii) 一給定偵檢器反應以時間爲函數之斜率(即,一給定偵檢 器反應之一階導數),(iii)該給定偵檢器反應以時間爲函 數之斜率的一變化(SP,該給定偵檢器反應之二階導 數),或(iv)來自每一該等偵檢器之(i)至(iii)的任何組 合。 -71- 201022666 36. 如申請專利範圍第35項之方法’其中該組合信號包括⑴ 每一該等偵檢器在一給定時間下之偵檢器反應値乘積’ (ii)該等偵檢器反應之一階導數在一給定時間下的乘 積,(iii)該等偵檢器反應之二階導數在一給定時間下的 乘積,或(iv)該⑴至(iii)之任何組合。 37. 如申請專利範圍第19項之方法,其中該液相層析系統 顯現出,在(i) 一偵檢器反應之偵檢、與(ii)根據由該偵 檢器反應所生成之一信號爲基礎來收集一樣本成分之一 ❹ 步驟間,小於大約2.0秒之最大時間延遲。 38. —種分析一樣本之方法,該方法之步驟包括: (a) 提供一非破壞性系統液相層析系統,其包括(i)一層 析管柱,(ii)二個或更多非破壞性偵檢器,且該系統中不 存有任何破壞性偵檢器,及(iii)一成分收集器,與該二 個或更多非破壞性偵檢器以流體連通;及 (b) 反應來自該二個或更多非破壞性偵檢器之偵檢器 φ 信號,收集一個或更多樣本成分。 39. 如申請專利範圍第38項之方法,其步驟尙包括: (a) 生成一組合信號’其包括來自每一該等偵檢器之一 偵檢反應組成部;及 (b) 反應該組合信號中之一變化,收集一新樣本成分。 4 0.如申請專利範圍第38項之方法,其尙包括: U)經由定位成可與至少一非破壞性偵檢器以流體連 通之一分流泵,主動地控制流動至該至少一非破壞性偵 -72- 201022666 檢器的流體。 41. 一種分析一樣本之方法,該方法之步驟包括: (a) 由一液相層析系統中之至少一偵檢器生成一偵檢 器信號,該偵檢器信號之生成係反應⑴―偵檢器反應以 時間爲函數之斜率(即,一偵檢器反應之—階導數),(ii) 該偵檢器反應以時間爲函數之斜率的一變化(即,該偵檢 器反應之二階導數),(iii)可任選地,一臨界偵檢器反應 値,或(iv)包括至少⑴或至少(ii)之該⑴至(iii)之任何組 合者;及 (b) 反應來自該至少一偵檢器之至少一偵檢器信號,收 集一個或更多樣本成分。 4 2.如申請專利範圍第41項之方法,其中該由至少一偵檢 器生成一偵檢器信號之步驟尙包括: U)針對(i)經歷一段時間之斜率資料,(ii)經歷一段時 間之斜率資料變化,(iii)可任選地,一臨界偵檢器反應 參 値’或(iv)該⑴至(iii)之任何組合,進行低通數値濾波, 以區分(i)經歷一段時間之斜率資料,(ii)經歷一段時間 之斜率資料變化’(iii)可任選地,一臨界偵檢器反應値, 或(iv)該⑴至(iii)之任何組合中之實際變化與該偵檢器 反應中可能的雜訊。 4 3.如申請專利範圍第41項之方法,其中該液相層析系統 包括二個或更多偵檢器。 44.如申請專利範圍第43項之方法,其步驟尙包括: -73- 201022666 (a) 生成一組合信號,其包括來自每一該等偵檢器之一 偵檢反應組成部;及 (b) 反應該組合信號中之一變化,收集一新樣本成分。 45. 如申請專利範圍第41項之方法,其尙包括: (a)經由定位成可與至少一偵檢器以流體連通之(i) 一 分流泵、及(ii) 一梭閥至少其中之一,主動地控制流至 該液相層析系統中之該至少一偵檢器的流體。 46. —種分析一樣本之方法,該方法之步驟包括: 參 U)將一樣本成分收集於一液相層析系統之一成分收 集器中,該成分收集器係作動式地調整成適應於識別、 接收、及處理來自至少一偵檢器之一個或更多信號,及 根據該一個或更多信號爲基礎,收集一個或更多樣本成 分。 47. 如申請專利範圍第1項至第46項任一項之方法,其中 該液相層析系統包括至少一偵檢器,其選自至少一紫外 φ 線偵檢器、至少一蒸發光散射偵檢器(ELSD)、至少一質 譜儀(MS)、至少一凝聚成核光散射偵檢器(CNLSD)、至 少一電暈放電偵檢器(CDD)、至少一折射率偵檢器 (RID)、至少一螢光偵檢器(FD)、至少一手性偵檢器 (CD)、或其任何組合。 48. —種電腦可讀式媒體,其上儲存有電腦可執行之指令, 以實施如申請專利範圍第1項至第47項任一項中所述之 方法步驟者。 -74- 201022666 49.一種能夠使用如申請專利範圍第1項至第47項任一項 之方法來分析一樣本之設備。 5 0.—種設備或設備組件,其能夠有助於使用如申請專利範 圍第1項至第47項任一項之方法所達成的一樣本分析 者。 51. —種設備或設備組件,其能夠有助於使用如申請專利範 圍第48項之電腦可讀式媒體所達成的一樣本分析者。 52. —種分析一樣本之設備,該設備包括: (a) 系統硬體,作動式地調整成適應於,由一液相層析 系統中之二個或更多偵檢器生成一組合信號,該組合信 號包括來自每一偵檢器之一偵檢反應組成部;及 (b) —成分收集器,作動式地調整成適應於,反應該組 合信號中之一變化,收集一新樣本成分。 53. 如申請專利範圍第52項之設備,其中該組合信號包括 一數學地使以下具有相關性(i)—偵檢器反應値,(ii) 一 φ 給定偵檢器反應以時間爲函數之斜率(即,一給定偵檢器 反應之一階導數),(iii)該給定偵檢器反應以時間爲函數 之斜率的一變化(即,該給定偵檢器反應之二階導數), 或(iv)來自每一該等偵檢器之⑴至(iii)的任何組合。 54. 如申請專利範圍第52項之設備,其中該組合信號包括(i) 每一該等偵檢器在一給定時間下之偵檢器反應値乘積, (ii)該等偵檢器反應之一階導數在一給定時間下的乘 積,(iii)該等偵檢器反應之二階導數在一給定時間下的 -75- 201022666 乘積,或(iv)該(i)至(iii)之任何組合。 55. 如申請專利範圍第52項之設備,該設備 多偵檢器,作動式地調整成適應於,在二 光學波長下觀察該樣本;及系統硬體,其 集器反應(i) 一偵檢器反應在一第一波長下 一偵檢器反應在一第二波長下之一變化, 檢器反應所表達之一組合反應在該等第一 的一變化,收集一新樣本成分。 參 56. 如申請專利範圍第52項之設備,該設備 泵或一梭閥,定位成可與至少一偵檢器以 主動地控制流動至該至少一偵檢器之流體 5 7.如申請專利範圍第52項之設備,該設備传 定位成可與至少一偵檢器以流體連通,且 動至該至少一偵檢器之流體者。 5 8.如申請專利範圍第57項之設備,其中該 Φ 包括一蒸發光散射偵檢器(ELSD〉。 59. 如申請專利範圍第52項之設備,其尙包 體供應裝置,該氣體或液體供應裝置係作 適應於,將一樣本整分自該梭閥傳輸至該i 60. 如申請專利範圍第59項之設備,其中該 規劃,以每1 0秒至少1樣本整分之一取榡 本整分自該樣本移開,而傳輸至該至少一 61. —種分析一樣本之設備,該設備包括: 包括二個或更 個或更多特定 允許該成分收 之一變化,(i i) 或(iii)該等偵 與第二波長下 尙包括一分流 流體連通,且 者。 包括一梭閥, 主動地控制流 至少一偵檢器 括一氣體或液 動式地調整成 5少一偵檢器。 梭閥係由程式 :頻率,將一樣 偵檢器。 -76- 201022666 (a) 至少一偵檢器,作動式地調整成適應於’在二個或 更多特定波長下觀察一樣本;及 (b) —成分收集器,作動式地調整成適應於’反應⑴ 一偵檢器反應在一第一波長下之一變化,(ii)一偵檢器反 應在一第二波長下之一變化,或(iii)該等偵檢器反應所 表達之一組合反應在該等第一與第二波長下的一變化’ 收集一新樣本。 62.如申請專利範圍第61項之設備,其中該成分收集器係 參 作動式地調整成適應於,反應(i) 一偵檢器反應在一第— 波長下之一變化,(ii) 一偵檢器反應在一第二波長下之一 變化,或(iii)該等偵檢器反應所表達之一組合反應在該 等第一與第二波長下的一變化,收集一新樣本。 6 3.如申請專利範圍第61項之設備,其中該至少一偵檢器 包括η個感測器,作動式地調整成適應於,在橫跨一吸 光頻譜之一範圍內的η個特定波長下觀察該樣本,其中 φ η係大於1之一整數;及反應⑴來自該η個感測器之η 個偵檢器反應中任一個的一變化,或(ii)由該η個偵檢器 反應所表達之一組合反應中的一變化,收集一新樣本。 64. 如申請專利範圔第63項之設備,其中該吸光頻譜之範 圍係一紫外線(UV)範圍》 65. 如申請專利範圍第63項之設備,其中該系統包括一單 一紫外線偵檢器,其單獨包括了 η個感測器、或其可結 合一個或更多附加偵檢器。 -77- 201022666 66.如申請專利範圍第61項之設備,其尙包括(i)一分流泵、 及(ii) 一梭閥至少其中之一,以主動地控制流動至該液相 層析系統中之至少一偵檢器的流體。 6 7.如申請專利範圍第66項之設備,其尙包括至少一梭閥, 主動地控制流動至該液相層析系統中之至少一偵檢器的 流體。 68. 如申請專利範圍第67項之設備,其中該至少一偵檢器 包括一蒸發光散射偵檢器(ELSD)。 ❹ 69. —種分析一樣本之設備,該設備包括: U)—層析管柱; (b) 一成分收集器; (c) 一第一偵檢器;及 (d) —分流泵或一梭閥,定位成與該第一偵檢器以流體 連通,該分流泵或梭閥係作動式地調整成適應於,主動 地控制流動至該第一偵檢器之流體。 φ 70.如申請專利範圍第69項之設備,其尙包括系統硬體, 允許該第一偵檢器傳送一致動信號至該分流泵或該梭 閥,來(i)致動該分流泵或該梭閥,(ii)解除致動該分流 泵或該梭閥,(iii)改變該分流泵或該梭閥之一個或更多 流動或壓力設定,或(iv)該⑴至(iii)之任何組合。 71.如申請專利範圍第70項之設備,其中該一個或更多流 動或壓力設定包括(i)一閥位置,(ii)分流泵或梭閥壓 力,(iii)提供至一閥之氣壓,或(iv)該⑴至(iii)之任何組 •78- 201022666 合。 72. 如申請專利範圍第70項之設備’其中該致動信號包括 一電氣信號、一氣動信號、一數位信號、或一無線信號。 73. 如申請專利範圍第69項之設備,其中該分流泵係定位 於~三通闕與該第一偵檢器之間。 7 4.如申請專利範圍第69項之設備’其中該第一偵檢器係 定位於一三通閥與該分流泵之間° 75.如申請專利範圍第69項之設備,其尙包括: e (e)—第二偵檢器。 76·如申請專利範圍第75項之設備’其中該分流泵或該梭 閥係在該第一偵檢器與該第一偵檢器之間’將一體積量 之流體流動分流者。 77. 如申請專利範圍第75項之設備,其中反應偵檢出該樣 本中之一組成物,該第二偵檢器係作動式地調整成適應 於,傳送一信號至該分流泵或該梭閥’以指示該分流泵 φ 或該梭閥起始或停止流體流動至該第一偵檢器。 78. 如申請專利範圍第69項之設備’其尙包括: (f) 一第二偵檢器,與一第二三通閥之一第二出口以流 體連通;及 (g) (vi) —第二分流泵或一第二梭閥,該第二分流泵或 該第二梭閥係主動地控制流動至該第二偵檢器之流體 者。 79. 如申請專利範圍第69項之設備,其中該成分收集器係 -79- 201022666 作動式地調整成適應於,反應來自該第一偵檢器之一個 或更多信號,來收集一個或更多樣本成分》 80. 如申請專利範圍第75項之設備,其中該成分收集器係 作動式地調整成適應於,反應來自(i)該第一偵檢器,(ii) 該第二偵檢器,或(iii)該等第一與第二偵檢器二者之一 個或更多偵檢器信號,來收集一個或更多樣本成分。 81. 如申請專利範圍第75項之設備,其中該設備係包括一 個或更多非破壞性偵檢器、且該系統中無任何破壞性偵 ❹ 檢器之一非破壞性系統。 8 2.如申請專利範圍第69項之設備,其尙包括系統硬體, 允許由至少一偵檢器生成一偵檢器信號,該偵檢器信號 之生成係反應(i) 一偵檢器反應以時間爲函數之斜率 (即,一偵檢器反應之一階導數),(Π)該偵檢器反應以時 間爲函數之斜率的一變化(即,該偵檢器反應之二階導 數),(iii)可任選地,一臨界偵檢器反應値,或(iv)包括 φ 至少⑴或至少(ii)之該⑴至(iii)之任何組合者。 83.如申請專利範圍第82項之設備,其中該系統硬體允許 針對(i)經歷一段時間之斜率資料,(ii)經歷一段時間之 斜率資料變化,(iii)可任選地,一臨界偵檢器反應値, 或(iv)該⑴至(iii)之任何組合,進行低通數値濾波,以區 分(i)經歷一段時間之斜率資料,(ii)經歷一段時間之斜 率資料變化,(iii)可任選地,一臨界偵檢器反應値,或 (iv)該(i)至(iii)之任何組合中之實際變化與該偵檢器反 -80- 201022666 應中可能的雜訊。 84. 如申請專利範圍第75項之設備,其尙包括系統硬體, 允許生成一組合信號,該組合信號包括來自每一該等偵 檢器之一偵檢反應組成部,該系統硬體係作動式地調整 成適應於,傳送一命令至該成分收集器,以反應該組合 信號中之一變化,收集一新樣本成分。 85. 如申請專利範圍第84項之設備,其中該組合信號包括 一數學地使以下具有相關性比(i)—偵檢器反應値,(ii) —給定偵檢器反應以時間爲函數之斜率(即,一給定偵檢 器反應之一階導數),(iii)該給定偵檢器反應以時間爲函 數之斜率的一變化(即,該給定偵檢器反應之二階導 數)’或(iv)來自每一該等偵檢器之(i)至(iii)的任何組 合。 8 6.如申請專利範圍第84項之設備,其中該組合信號包括(i) 每一該等偵檢器在一給定時間下之偵檢器反應値乘積, (ii)該等偵檢器反應之一階導數在一給定時間下的乘 積,(iii)該等偵檢器反應之二階導數在一給定時間下的 乘積,或(iv)該⑴至(iii)之任何組合。 87.如申請專利範圍第69項之設備,該設備包括至少一偵 檢器,作動式地調整成適應於,在二個或更多特定波長 下観察一樣本;及系統硬體,允許該成分收集器,作動 式地調整成適應於,反應⑴一偵檢器反應在一第一波長 下之一變化’(ii) 一偵檢器反應在一第二波長下之一變 -81- 201022666 化,或(iii)該等偵檢器反應所表達之一組合反應在該等 第一與第二波長下的一變化’收集一新樣本成分。 88.如申請專利範圍第69項之設備’該設備包括一單一偵 檢器,其包括η個感測器’作動式地調整成適應於’在 橫跨一吸光頻譜之一範圍內的η個特定波長下觀察該樣 本,其中η係大於1之一整數;及系統硬體’允許該成 分收集器,作動式地調整成適應於’反應⑴該η個特定 紫外線波長下之η個偵檢器反應中任一個的一變化’或 (ii)由該η個偵檢器反應所表達之一組合反應中的一變 化,來收集一新樣本成分。’ 8 9.如申請專利範圍第69項之設備’該成分收集器係作動 式地調整成適應於識別、接收、及處理來自至少一偵檢 器之一個或更多信號,以及根據該一個或更多信號爲基 * 礎,收集一個或更多樣本成分。 9 0.如申請專利範圍第69項之設備,該設備顯現出,在⑴ 0 一偵檢器反應之偵檢、與(ii)根據由該偵檢器反應所生成 之一信號爲基礎來收集一樣本成分之一步驟間,小於大 約2.0秒之最大時間延遲。 91. 一種分析一樣本之設備,該設備包括: (a)系統硬體,允許由一液相層析系統中之至少一偵檢 器生成一偵檢器信號,該偵檢器信號之生成係反應(i) — 偵檢器反應以時間爲函數之斜率(即,一偵檢器反應之一 階導數),(ii)該偵檢器反應以時間爲函數之斜率的一變 -82- 201022666 化(即,該偵檢器反應之二階導數),(iii)可任選地’一 臨界偵檢器反應値,或(iv)包括至少⑴或至少(ii)之該⑴ 至(iii)之任何組合者。 92.如申請專利範圍第91項之設備,其中該系統硬體允許 針對(i)經歷一段時間之斜率資料,(ii)經歷一段時間之 斜率資料變化,(iii)可任選地,一臨界偵檢器反應値, 或(iv)該(i)至(iii)之任何組合,進行低通數値濾波,以區 分(i)經歷一段時間之斜率資料,(ii)經歷一段時間之斜 e 率資料變化,(iii)可任選地,一臨界偵檢器反應値,或 (iv)該(i)至(iii)之任何組合中之實際變化與該偵檢器反 應中可能的雜訊。 9 3.如申請專利範圍第91項之設備,該設備尙包括一成分 收集器,作動式地調整成適應於,反應來自至少一偵檢 器之該至少一偵檢器信號,收集一個或更多樣本成分。 94. 如申請專利範圍第91項之設備,該設備包括二個或更 φ 多偵檢器。 95. 如申請專利範圍第94項之設備,其中該系統硬體允許 生成一組合信號,包括來自每一該等偵檢器之一偵檢反 應組成部。 96. 如申請專利範圍第95項之設備,其中該組合信號包括 一數學地使以下具有相關性(i) 一偵檢器反應値,(ii) — 給定偵檢器反應以時間爲函數之斜率(即,一給定偵檢器 反應之一階導數),(iii)該給定偵檢器反應以時間爲函數 -83- 201022666 之斜率的一變化(即,該給定偵檢器反應之二階導數), 或(iv)來自每一該等偵檢器之(i)至(iii)的任何組合。 97. 如申請專利範圍第95項之設備,其中該組合信號包括⑴ 每一該等偵檢器在一給定時間下之偵檢器反應値乘積, (ii)該等偵檢器反應之一階導數在一給定時間下的乘 積,(iii)該等偵檢器反應之二階導數在一給定時間下的 乘積,或(iv)該⑴至(iii)之任何組合。 98. 如申請專利範圍第95項之設備,該設備尙包括一成分 〇 收集器,作動式地調整成適應於,反應該組合信號中之 一變化,來收集一新樣本成分。 9 9.如申請專利範圍第91項之設備,該設備包括⑴一層析 管柱,(ii)二個或更多非破壞性偵檢器,且該系統中不存 有任何破壞性偵檢器,及(iii)一成分收集器,與該二個 或更多非破壞性偵檢器以流體連通。 100. 如申請專利範圍第94項之設備,該設備包括一分流泵 φ 或一梭閥,定位成可與至少一偵檢器以流體連通,且主 動地控制流動至該至少一偵檢器之流體者。 101. —種分析一樣本之設備,該設備包括: (a)—液相層析系統中之一成分收集器中,該成分收 集器係作動式地調整成適應於識別、接收、及處理來自 至少一偵檢器之一個或更多信號,以及根據該一個或更 多信號爲基礎,收集一個或更多樣本成分。 102·如申請專利範圍第52項至第101項任一項之設備,其 -84- 201022666 中該設備包括至少一偵檢器’其選自至少一紫外線偵檢 器、至少一蒸發光散射偵檢器(ELSD)、至少一質譜儀 (MS)、至少一凝聚成核光散射偵檢器(CNLSD)、至少一 電暈放電偵檢器(CDD)、至少一折射率偵檢器(RID)、至 少一螢光偵檢器(FD)、至少一手性偵檢器(CD)、或其任 何組合。 103. —種使用層析法分析一樣本之方法,該方法之步驟包 括: (a) 使用至少一偵檢器觀察包括至少一非載色待測化 合物之該樣本;及 (b) 反應一偵檢器反應中關於該非載色化合物之一變 化,將一新樣本成分收集於一成分收集器中。 104. 如申請專利範圍第103項之方法,其中該樣本係由一 非載色移動相組成。 105. —種使用層析法分析一流體樣本之設備,該設備包括: φ (a)至少一偵檢器,其能夠偵檢出該樣本中之載色與 非載色待測化合物;及 (b)—成分收集器,其能夠反應一偵檢器反應中關於 該非載色化合物之一變化。 106. 如申請專利範圍第1〇5項之設備,其中該樣本係由一 非載色移動相組成。 107. —種使用層析法分析一流體樣本之方法,該方法之步 驟包括: -85- 201022666 (a) 提供一第一流體; (b) 使用一梭閥,自該第一流體移開一整分流體樣 本,而大致不影響該第一流體之流動特性;; (c) 使用至少一偵檢器來觀察該流體整分樣本;及 (d) 反應一偵檢器反應中之一變化,自該第一流體收 集一新樣本成分於一成分收集器中。 10 8.如申請專利範圍第107項之方法,其中通過該梭閥之 該第一流體流動係大致呈層流。 109. 如申請專利範圍第107項之方法,其中通過該梭閥之 該第一流體壓力係大致不增加或大致保持定値 110. 如申請專利範圍第107項之方法,其中該方法尙包括 一第二流體’將該整分流體樣本運送至該(等)偵檢器。 111. 如申請專利範圍第107項之方法,其中通過該梭閥之 該第二流體流動係大致呈層流。 112. 如申請專利範圍第107項之方法,其中通過該梭閥之 0 該第二流體壓力係大致不增加或大致保持定値。 113. —種使用層析法分析一流體樣本之設備,該設備包括: (a) —第一流體路徑; (b) 至少一偵檢器,能夠分析該流體樣本;及 (c) 一梭閥,可將一整分流體樣本自該第一流體路徑 轉運至該偵檢器,而大致不影響通過該第一流體路徑之 流體的流體特性。 1 14.如申請專利範圍第113項之設備,其中通過該閥之該 -86- 201022666 第一流體路徑至少一部分係呈大致線性或筆直。 115.如申請專利範圍第113項之設備,其中通過該第一流 體路徑之流體壓力係大致不增加或大致保持定値。 I 16.如申請專利範圍第113項之設備,其中該設備尙包括 一第二流體路徑,將該整分流體樣本運送至該(等)偵檢 器》 117.如申請專利範圍第116項之設備,其中通過該閥之該 第二流體路徑至少一部分係呈大致線性或筆直。 參 II 8.如申請專利範圍第116項之設備,其中通過該第二流 體路徑之流體壓力係大致不增加或大致保持定値。 119. 如申請專利範圍第113項之設備,其中該設備包括一 整分凹坑,使得該第一流體路徑與該整分凹坑大致平 行。 120. —種使用層析法分析一流體樣本之設備,該設備包括: U)—第一流體路徑; . (b)—第二流體路徑; (c) 至少一偵檢器,其能夠分析該樣本;及 (d) —梭閥,可將一整分樣本自該第一流體路徑轉運至 該第二流體路徑,且同時維持通過該該梭閥之一連續第 二流體路徑。 12 1.如申請專利範圍第120項之設備,其中通過該梭閥之 該第一流體路徑及/或第二流體路徑中的流體壓力係大 致不增加及/或大致保持定値。 -87- 201022666 1 2 2.如申請專利範圍第120項之設備,其中該設備包括一 整分凹坑’使得該第一流體路徑與該整分凹坑大致平 行。 123· —種使用層析法分析一流體樣本之方法,該方法之步 驟包括: U)提供自一層析管柱流出之一第—流體; (b) 提供一第二流體,將該流體樣本運送到至少一偵 檢器; 參 (c) 使用一梭閥,將一整分樣本自該第一流體移至該 第二流體,且同時維持該第二流體通過該梭閥之一連續 路徑; (d) 使用至少一偵檢器來觀察該整分樣本;及 (e) 反應一偵檢器反應中之一變化,自該第一流體收 集一新樣本成分於一成分收集器中。 124. 如申請專利範圍第123項之方法,其中當該整分樣本 Q 自該第一流體移開且轉運至該第二流體時,該第一流體 通過該梭閥之一連續流動路徑,仍將維持。 125. 如申請專利範圍第123項之方法,其中當該整分樣本 自該第一流體移開且轉運至該第二流體時,該等第一及 第二流體通過該梭閥之連續流動路徑,仍將維持。 126. —種使用層析法分析一流體樣本之方法,該方法之步 驟包括: (a)提供包括有該樣本之一流束; -88 - 201022666 (b) 使用一通用載運流體’自該流束移開一整分該樣 本;及 (c) 使用至少一偵檢器,來分析該通用載運流體中之 該整分, (d) 其中該通用載運流體包括一氣體或—液體,其可 溶混於有機溶劑及水中、具較低揮發性、且爲非載色者。 127. 如申請專利範圍第126項之方法,其中該載運流體包 括異丙醇、丙酮、甲醇、乙醇、丙醇、丁醇、異丁醇、 參 四氫呋喃、或其混合物。 128. 如申請專利範圍第126項之方法,其中該載運流體包 括異丙醇。 129. —種使用快速層析法分析一流體樣本之設備,該設備 包括’· (a)—蒸發微粒偵檢器’其能夠偵檢出該樣本中之各 別化合物;及 φ (b)—成分收集器,其能夠反應關於該'偵檢出之化合 物的一偵檢器反應中之一變化, (c)其中該蒸發微粒偵檢器係該設備中之唯一偵檢 器。 130. 如申請專利範圍第129項之設備,其中該蒸發微粒偵 檢器能夠偵檢化學成分、化學結構、分子重量、或其組 合。 131·如申請專利範圍第129項之設備,其中該蒸發微粒偵 -89- 201022666 檢器包括蒸發光散射偵檢器、凝聚成核光散射偵檢器、 或質譜儀。 132.—種使用快速層析法分析一流體樣本之方法,該方法 之步驟包括·: (a) 使用能夠偵檢出各別化合物一蒸發微粒偵檢器, 來觀察該樣本;及 (b) 反應關於該化合物之一偵檢器反應中的一變化, 將一新樣本成分收集於一成分收集器中, (c) 其中該蒸發微粒偵檢器係唯一用於分析該樣本之 偵檢器。 13 3.如申請專利範圍第132項之方法,其中該蒸發微粒偵 檢器能夠偵檢化學成分、化學結構、分子重量、或其組 合。 134.如申請專利範圍第132項之方法,其中該蒸發微粒偵 檢器包括蒸發光散射偵檢器、凝聚成核光散射偵檢器、 . 或質譜儀。 -90-201022666 VII. Patent application scope: 1.  A method of analyzing the same method 'The steps of the method include: (a) generating a combined signal from two or more detectors in a liquid chromatography system, the combined signal including from each of the detectors a reaction component; and (b) reacting one of the combined signals to convert a new sample into a component collector. 2.  As in the method of claim 1, the generating of a combined signal U) mathematically correlates: (i) a detector response 斜率 a given detector response as a function of time (ie, a given derivative response () a change in the slope of the given detector response by the number of times (ie, the second derivative of the given detector response or (iv) from each of the Any combination of (1) to (iii) of the detector.  The method of claim 1, wherein the combined signal packet of each of the detectors at a given time is multiplied by a detector (ii) the first derivative of the detector response is in a The product is given at a given time, (iii) the second derivative of the detector response is accumulated at a given time, or (iv) any combination of (1) to (iii).  The method of claim 2, the steps comprising: (a) using at least one detector to observe the sample at two or more specific optical waves to produce at the two or more specific optical wavelengths Two or more detectors react; the combined signal includes a detection counter, which is from the set of detection collections of the two or more specific optical wavelengths, (ii) the detection is The function), including (1) product, multiply by the length of the group should be two -65-201022666 or more detector responders. 5.  The method of claim 4, wherein the at least the detector detects two or more specific optical wavelengths including at least an ultraviolet (UV) detector and the combined signal comprises (i) from the ultraviolet detection Detecting a detection reaction component of the two or more detectors at the two or more specific optical wavelengths, and (ii) detecting from one of the Evaporative Light Scattering Detectors (ELSD) Check the reaction components. 6.  The method of claim 1, wherein the combined signal comprises (1) a detection reaction component from one of the at least one ultraviolet detector, and (ii) one of the at least one evaporative light scattering detector (ELSD) Check the reaction components. 7.  The method of claim 1, wherein the method comprises: (a) via (i) a shunt pump, (ii) a shuttle valve, or (iii) positioned in fluid communication with the at least one detector. Both (1) and (ii) actively control the flow of fluid to the at least one detector in the liquid chromatography system. Φ 8. The method of claim 1, wherein: (a) actively controlling the flow into the liquid chromatography system via a shuttle valve positioned in fluid communication with the at least one detector A detector's fluid. 9.  The method of claim 8, wherein the at least one detector comprises an evaporative light scattering detector (ELSD). 10.  For example, the method of claim 8 includes: (a) using air to transfer the same split from the shuttle valve to the at least one -66-201022666 detector. 11. The method of claim 8, wherein the shuttle valve is moved from the sample to the sample at a sampling frequency of at least 1 sample per 10 seconds (s). A detective. 12.  - A method of analyzing the same method, the steps of the method comprising: (a) using at least one detector, and observing the same at two or more specific wavelengths: and (b) reacting (i) a detector The reaction changes at one of the first wavelengths, (ii) the Detector-Detector reaction changes at one of the second wavelengths, or (iii) the one of the detector responses expresses a combination reaction at the A new sample component is collected in a component collector at a change from the second wavelength. 13.  The method of claim 12, wherein the steps include: (a) reaction (i) - the detector response changes at one of the first wavelengths, (ii) a detector reacts at - the second wavelength The next one changes 'or' a change in the combination of one of the first and second wavelengths φ expressed by the detector response, and a new sample component is collected in the component collector. 14.  The method of claim 12, wherein the steps include: (a) using at least one of the at least one detectors to observe the n specific wavelengths across a range of one of the optical absorption spectra Sample 'where η is greater than one integer of 1; and (b) reaction (1) a change from any of the n detector responses of the n sensors, or (丨丨) by the n detection A change in one of the combined reactions expressed by the reaction, a new sample component is collected in the component collector -67-201022666 〇15.  The method of claim 14, wherein the range of the absorption spectrum is a range of ultraviolet (UV). 16.  The method of claim 14, wherein the system comprises - a single ultraviolet detector - which separately includes n sensors, or it may incorporate one or more additional detectors. 17.  The method of claim 14, wherein: φ (a) is via (1) a shunt pump, (ii) a shuttle valve, or (iii) positioned in fluid communication with the at least one detector. (1) and (ii), actively controlling the flow of fluid to the at least one detector in the liquid chromatography system. 18.  The method of claim 14, wherein the method comprises: (a) actively controlling the flow into the liquid chromatography system via a shuttle valve positioned in fluid communication with the at least one detector A detector's fluid. 19.  A method of analyzing the same method, the method comprising the steps of: providing a liquid chromatography system comprising: (1) a chromatography column '(ii) a component collector, and (iii) - a first detection And (b) actively controlling the flow of fluid to the first detector via an (iv)-split pump or a shuttle valve positioned in fluid communication with the first detector. 20.  The method of claim 19, wherein the step of actively controlling the flow of fluid to the first detector comprises: U) transmitting an actuation signal to the split pump or shuttle valve to (1) actuate the split pump or shuttle Valve, (Π) deactivates the split pump or shuttle valve '(111) to change one or more flow or pressure settings of the -68-201022666 split pump or shuttle valve, or (iv) the (1) to (iii) Any combination. twenty one.  The method of claim 20, wherein the one or more flow or pressure settings comprise (i) a valve position, (ii) a split pump or shuttle valve pressure, (iii) a pressure supplied to a valve, or ( Iv) any combination of (1) to (iii). twenty two.  The method of claim 20, wherein the actuation signal comprises A - an electrical signal, a pneumatic signal, a digital signal, or a wireless signal. twenty three. The method of claim 19, wherein the step of actively controlling the flow of fluid to the first detector comprises pumping fluid to the first detector via the split pump. twenty four. The method of claim 19, wherein the step of actively controlling the flow of fluid to the first detector comprises dragging the fluid through the first detector through the split pump. 2 5. The method of claim 19, wherein the step of actively controlling the flow of fluid to the first detector comprises providing one or more samples to the first detector via a shuttle valve By. 26.  The method of claim 19, wherein the liquid chromatography system includes (v) a second detector; the step of actively controlling the fluid flowing to the first detector includes, at the first Between the detector and the second detector, a volume of fluid is diverted. 27.  The method of claim 19, wherein the liquid chromatography system comprises (v) a second detector; the method comprises the steps of: -69- 201022666 (a) reacting the second detector Detecting a composition of the same type, transmitting a signal to the shunt pump or the shuttle valve to indicate that the shunt pump or the shuttle valve initiates or stops fluid flow to the first detector. 28. The method of claim 19, wherein the liquid chromatography system comprises (v) - a second detector, and (Vi) - a second split pump or a second shuttle valve; steps of the method The method includes: (a) actively controlling fluid flowing to the second detector via the second bypass pump or the second shuttle valve. Φ 2 9. In the method of claim 19, the steps of the method include: (a) reacting one or more signals from the first detector to collect one or more sample components. 3 0. The method of claim 26, the steps comprising: (a) reacting from (i) the first detector, (ii) the second detector, or (iii) the first and the One or more of the second detectors, one or more detector signals, collect one or more sample components. Φ 31. The method of claim 26, wherein the liquid chromatography system comprises one or more non-destructive detectors and is free of any non-destructive system of any destructive detector. 32. For example, in the method of claim 19, the steps include: (a) generating a detector signal by at least one detector, the generation of the detector signal (i) a detector response in time Is the slope of the function (ie, the first derivative of a detector response), (ii) a change in the slope of the detector response as a function of time (ie, the second derivative of the detector response -70- 201022666) The number '(iii) optionally 'reaches or exceeds a critical detector response 値, or (iv) includes at least (i) or at least (iii) any combination of (1) to (iii). 33. The method of claim 32, wherein the step of generating a detector signal by the at least one detector comprises: (a) for (i) a slope of the data over a period of time, (ii) a period of time Time slope data change, (iii) optionally, a critical detector response, or (iv) any combination of (1) to (iii), performing low pass 値 filtering to distinguish (i) from a period of time Slope data of time, (ii) experiencing - slope data change over time - (iii) optionally, - critical detector response 値, or (iv) actual change in any combination of (1) to (iii) Possible noise in response to the detector. 34. The method of claim 26, wherein the steps include: (a) generating a combined signal comprising one of the detection reaction components from each of the detectors; and (b) reacting the combined signal One change, collecting a new sample component. 3 5. As in the method of claim 34, the step of generating a combined signal comprises: (a) mathematically making the following correlation (1) a detector response, (ii) a given detector response in time The slope of the function (ie, a derivative of a given detector response), (iii) a change in the slope of the given detector response as a function of time (SP, the second order of the given detector response) Derivative), or (iv) any combination of (i) to (iii) from each of the detectors. -71- 201022666 36.  The method of claim 35, wherein the combined signal comprises (1) a detector reaction 値 product of each of the detectors at a given time' (ii) a first derivative of the detector response The product at a given time, (iii) the product of the second derivative of the detector response at a given time, or (iv) any combination of (1) to (iii). 37.  The method of claim 19, wherein the liquid chromatography system exhibits, in (i) a detection of a detector response, and (ii) a signal generated by the reaction of the detector is The basis is to collect one of the same ingredients ❹ between steps, less than about 2. The maximum time delay of 0 seconds. 38.  - A method of analyzing the same, the steps of the method comprising: (a) providing a non-destructive system liquid chromatography system comprising (i) a chromatography column, (ii) two or more non-destructive a sex detector, and the system does not have any destructive detectors, and (iii) a component collector in fluid communication with the two or more non-destructive detectors; and (b) a reaction A detector φ signal from the two or more non-destructive detectors collects one or more sample components. 39.  For example, in the method of claim 38, the steps include: (a) generating a combined signal 'which includes one of the detection reaction components from each of the detectors; and (b) reacting the combined signal One change, collecting a new sample component. 4 0. The method of claim 38, wherein the method comprises: U) actively controlling the flow to the at least one non-destructive detection via a split pump positioned in fluid communication with the at least one non-destructive detector. 72- 201022666 The fluid of the detector. 41.  A method for analyzing the same method, the method comprising the steps of: (a) generating a detector signal from at least one detector in a liquid chromatography system, the generation of the detector signal (1) - detection The slope of the response as a function of time (ie, the derivative of a detector reaction), (ii) a change in the slope of the detector response as a function of time (ie, the second derivative of the detector response) And (b) optionally, a critical detector reaction 値, or (iv) includes at least (1) or at least (ii) any combination of the (1) to (iii); and (b) the reaction comes from the at least At least one detector signal of a detector collects one or more sample components. 4 2. The method of claim 41, wherein the step of generating a detector signal by the at least one detector comprises: U) a slope for (i) a period of time, (ii) a slope of a period of time Data change, (iii) optionally, a critical detector response parameter or (iv) any combination of (1) to (iii), performing low pass 値 filtering to distinguish (i) over a period of time Slope data, (ii) slope data changes over a period of time '(iii) optionally, a critical detector response 値, or (iv) actual changes in any combination of (1) to (iii) with the Detect Possible noise in the detector response. 4 3. The method of claim 41, wherein the liquid chromatography system comprises two or more detectors. 44. For example, the method of claim 43 includes the steps of: -73- 201022666 (a) generating a combined signal comprising one of the detection reaction components from each of the detectors; and (b) A change in one of the signals should be combined to collect a new sample component. 45.  The method of claim 41, wherein: (a) at least one of (i) a shunt pump, and (ii) a shuttle valve positioned in fluid communication with the at least one detector, The fluid flowing to the at least one detector in the liquid chromatography system is actively controlled. 46.  As an analysis of the same method, the method comprises the steps of: collecting the same component in a component collector of a liquid chromatography system, the component collector being operatively adjusted to be adapted to the identification, Receiving, and processing one or more signals from at least one detector, and collecting one or more sample components based on the one or more signals. 47.  The method of any one of claims 1 to 46, wherein the liquid chromatography system comprises at least one detector selected from the group consisting of at least one ultraviolet ray detector, at least one evaporative light scattering detection (ELSD), at least one mass spectrometer (MS), at least one condensed nucleation light scattering detector (CNLSD), at least one corona discharge detector (CDD), at least one refractive index detector (RID), At least one fluorescent detector (FD), at least one chiral detector (CD), or any combination thereof. 48.  A computer readable medium having stored thereon computer executable instructions for performing the method steps as set forth in any one of claims 1 to 47. -74- 201022666 49. A device capable of analyzing the same as the method of any one of claims 1 to 47. 5 0. A device or device component capable of facilitating the use of the same analyst as that achieved by the method of any one of claims 1 to 47. 51.  A device or device component that can facilitate the use of the present analyst as defined by the computer readable medium of claim 48 of the patent application. 52.  An apparatus for analyzing an apparatus comprising: (a) a system hardware operatively adapted to generate a combined signal from two or more detectors in a liquid chromatography system The combined signal includes a detection reaction component from one of each of the detectors; and (b) a component collector operatively adapted to, responsive to, one of the combined signals, to collect a new sample component. 53.  The apparatus of claim 52, wherein the combined signal comprises a mathematically correlative (i)-detector response, (ii) a φ given detector response as a function of time slope (ie, a given detector response, a derivative of the order), (iii) a change in the slope of the given detector response as a function of time (ie, the second derivative of the given detector response), Or (iv) any combination of (1) to (iii) from each of the detectors. 54.  The device of claim 52, wherein the combined signal comprises (i) a detector reaction 値 product of each of the detectors at a given time, (ii) one of the detector responses The product of the order derivative at a given time, (iii) the product of the second derivative of the detector response at -75-201022666 at a given time, or (iv) any of (i) to (iii) combination. 55.  For example, in the device of claim 52, the device has multiple detectors that are operatively adjusted to accommodate the observation of the sample at two optical wavelengths; and the system hardware, the collector reaction (i) a detector The reaction changes at a first wavelength under a detector response at a second wavelength, and the detector reaction expresses a combination of one of the first changes in the first reaction to collect a new sample component. Reference 56.  7. The apparatus of claim 52, the equipment pump or a shuttle valve positioned to interact with at least one detector to actively control fluid flow to the at least one detector. The device of claim 52, wherein the device is positioned to be in fluid communication with the at least one detector and to the fluid of the at least one detector. 5 8. For example, the device of claim 57, wherein the Φ comprises an evaporative light scattering detector (ELSD).  The apparatus of claim 52, wherein the gas supply device is adapted to transfer the same split from the shuttle valve to the i 60.  For example, in the device of claim 59, wherein the plan is to take at least one sample of the entire sample every 10 seconds, the whole point is removed from the sample and transmitted to the at least one.  An apparatus for analyzing an apparatus comprising: including two or more specific ones that permit the change of the component, (ii) or (iii) the detecting and the second wavelength to include a diverting fluid Connected, and. A shuttle valve is included to actively control the flow of at least one detector including a gas or a hydraulically adjusted to less than one detector. The shuttle valve is programmed by the program: the frequency will be the same as the detector. -76- 201022666 (a) At least one detector, operatively adapted to 'see the same at two or more specific wavelengths; and (b) - the component collector, operatively adjusted to accommodate 'Reaction (1) a detector response changes at one of the first wavelengths, (ii) a detector response changes at one of the second wavelengths, or (iii) one of the detector responses A new sample is collected by a change in the combination of the first and second wavelengths. 62. For example, in the device of claim 61, wherein the component collector is dynamically adjusted to suit, the reaction (i) a detector response changes at one of the first wavelengths, (ii) a detection The reactor reacts at one of the second wavelengths, or (iii) a change in the combination of the first and second wavelengths of the combination of the detectors, and a new sample is collected. 6 3. The apparatus of claim 61, wherein the at least one detector comprises n sensors, operatively adapted to be adapted to observe the n specific wavelengths across a range of one of the light absorption spectra a sample, wherein φ η is greater than one integer of 1; and (1) a change from any of the n detector responses of the n sensors, or (ii) expressed by the n detector responses One of the changes in the combined reaction collects a new sample. 64.  For example, the device of claim 63, wherein the range of the absorption spectrum is an ultraviolet (UV) range.  The apparatus of claim 63, wherein the system comprises a single ultraviolet detector comprising n sensors individually or in combination with one or more additional detectors. -77- 201022666 66. The apparatus of claim 61, comprising at least one of (i) a split pump, and (ii) a shuttle valve to actively control at least one of the detections flowing into the liquid chromatography system Fluid. 6 7. The apparatus of claim 66, further comprising at least one shuttle valve for actively controlling fluid flowing to at least one of the detectors in the liquid chromatography system. 68.  The device of claim 67, wherein the at least one detector comprises an evaporative light scattering detector (ELSD). ❹ 69.  An apparatus for analyzing an apparatus comprising: U) a chromatography column; (b) a component collector; (c) a first detector; and (d) a diverter pump or a shuttle valve, Positioned in fluid communication with the first detector, the split pump or shuttle valve is operatively adapted to actively control fluid flow to the first detector. Φ 70. The device of claim 69, wherein the device includes a system hardware that allows the first detector to transmit an actuating signal to the shunt pump or the shuttle valve to (i) actuate the shunt pump or the shuttle valve (ii) deactuating the split pump or the shuttle valve, (iii) changing one or more flow or pressure settings of the split pump or the shuttle valve, or (iv) any combination of the (1) to (iii). 71. The apparatus of claim 70, wherein the one or more flow or pressure settings comprise (i) a valve position, (ii) a split pump or shuttle valve pressure, (iii) a pressure supplied to a valve, or ( Iv) Any of the groups (1) to (iii) • 78- 201022666. 72.  The device of claim 70, wherein the actuation signal comprises an electrical signal, a pneumatic signal, a digital signal, or a wireless signal. 73.  The device of claim 69, wherein the shunt pump is positioned between the three-way port and the first detector. 7 4. For example, the apparatus of claim 69 wherein the first detector is located between a three-way valve and the split pump. For example, the equipment of claim 69 of the patent scope includes: e (e) - the second detector. 76. The apparatus of claim 75, wherein the split pump or the shuttle valve is between the first detector and the first detector to divert a volume of fluid flow. 77.  The apparatus of claim 75, wherein the reaction detects one of the components of the sample, and the second detector is operatively adapted to transmit a signal to the shunt pump or the shuttle valve To indicate that the split pump φ or the shuttle valve starts or stops fluid flow to the first detector. 78.  The apparatus of claim 69 includes: (f) a second detector in fluid communication with a second outlet of a second three-way valve; and (g) (vi) - second A split pump or a second shuttle valve, the second split pump or the second shuttle valve actively controls the fluid flowing to the second detector. 79.  An apparatus as claimed in claim 69, wherein the component collector system -79-201022666 is operatively adapted to receive one or more signals from the first detector to collect one or more samples Ingredients 80.  The apparatus of claim 75, wherein the component collector is operatively adapted to be adapted to (i) the first detector, (ii) the second detector, or (iii) One or more detector signals of the first and second detectors to collect one or more sample components. 81.  The device of claim 75, wherein the device comprises one or more non-destructive detectors and the system is non-destructive without any destructive detector. 8 2. The device of claim 69, which includes the system hardware, allows a detector signal to be generated by at least one detector, the detector signal generation reaction (i) a detector response time Is the slope of the function (ie, the first derivative of a detector response), (Π) the change in the slope of the detector response as a function of time (ie, the second derivative of the detector response), (iii) Optionally, a critical detector reaction 値, or (iv) includes any combination of φ at least (1) or at least (ii) of (1) to (iii). 83. For example, the device of claim 82, wherein the system hardware allows for (i) slope data for a period of time, (ii) slope data changes over a period of time, (iii) optionally, a critical detection値, or (iv) any combination of (1) to (iii), performing low-pass 値 filtering to distinguish between (i) slope data over a period of time, (ii) slope data changes over a period of time, (iii) Optionally, a critical detector response 値, or (iv) the actual variation in any combination of (i) to (iii) and the possible noise of the detector counter-80-201022666. 84.  The device of claim 75, which includes a system hardware, is configured to generate a combined signal, the combined signal comprising a detection reaction component from one of each of the detectors, the system hard-actingly Adjusted to accommodate, transmitting a command to the component collector to reflect a change in one of the combined signals to collect a new sample component. 85.  The apparatus of claim 84, wherein the combined signal comprises a mathematically having a correlation ratio (i) - a detector response 値, (ii) - a slope of a given detector response as a function of time (ie, a given derivative of the detector response), (iii) a change in the slope of the given detector response as a function of time (ie, the second derivative of the given detector response) Or (iv) any combination of (i) to (iii) from each of the detectors. 8 6. The apparatus of claim 84, wherein the combined signal comprises (i) a detector reaction 値 product of each of the detectors at a given time, (ii) one of the detector responses The product of the order derivative at a given time, (iii) the product of the second derivative of the detector response at a given time, or (iv) any combination of (1) to (iii). 87. An apparatus as claimed in claim 69, the apparatus comprising at least one detector, operatively adapted to adapt to observing the same at two or more specific wavelengths; and system hardware allowing the component collector Actually adjusted to accommodate, reaction (1) a detector response changes at one of the first wavelengths' (ii) a detector reaction at one of the second wavelengths - 81- 201022666, or (iii) collecting a new sample component from a change in the combination of the first and second wavelengths expressed by one of the detector responses. 88. Apparatus as claimed in claim 69, the apparatus comprising a single detector comprising n sensors configured to be adapted to 'nize a particular wavelength across a range of one absorption spectrum Observing the sample, wherein the η system is greater than one integer of 1; and the system hardware 'allows the component collector to be operatively adjusted to accommodate the reaction (1) of the n detector responses at the n specific UV wavelengths A change in either one or (ii) a change in one of the combined reactions expressed by the n detector responses to collect a new sample component. ’ 8 9. The device of claim 69, wherein the component collector is operatively adapted to identify, receive, and process one or more signals from the at least one detector, and based on the one or more signals Base one or more sample components. 9 0. For example, in the device of claim 69, the device exhibits the same component as the detection of the (1) 0 detector response and (ii) the signal generated by the reaction of the detector. Between one step, less than about 2. The maximum time delay of 0 seconds. 91.  An apparatus for analyzing an apparatus comprising: (a) a system hardware that allows a detector signal to be generated by at least one detector in a liquid chromatography system, the detector signal generating system reaction ( i) – the detector response is a function of the slope of time (ie, the first derivative of a detector response), (ii) a change in the slope of the detector response as a function of time -82- 201022666 ( That is, the second derivative of the detector response), (iii) optionally 'a critical detector response 値, or (iv) includes at least (1) or at least (ii) any combination of the (1) to (iii) By. 92. For example, the device of claim 91, wherein the system hardware allows for (i) slope data for a period of time, (ii) slope data changes over a period of time, (iii) optionally, a critical detection値, or (iv) any combination of (i) to (iii), performing low-pass 値 filtering to distinguish between (i) slope data over a period of time, (ii) oblique e-rate data over a period of time The change, (iii) optionally, a critical detector response, or (iv) the actual change in any combination of (i) to (iii) may be a possible noise in the reaction with the detector. 9 3. The apparatus of claim 91, wherein the apparatus includes a component collector operatively adapted to: react to the at least one detector signal from the at least one detector to collect one or more sample components . 94.  For equipment of claim 91, the apparatus includes two or more detectors. 95.  The device of claim 94, wherein the system hardware allows for generating a combined signal, including a detection reaction component from one of each of the detectors. 96.  The apparatus of claim 95, wherein the combined signal comprises a mathematically correlated correlation (i) a detector response, (ii) - a slope of the given detector response as a function of time ( That is, a given detector response is a derivative of the order), (iii) a change in the slope of the given detector response as a function of time -83- 201022666 (ie, the second order of the given detector response) Derivative), or (iv) any combination of (i) to (iii) from each of the detectors. 97.  The device of claim 95, wherein the combined signal comprises (1) a detector reaction 値 product of each of the detectors at a given time, (ii) a first derivative of the detector response The product at a given time, (iii) the product of the second derivative of the detector response at a given time, or (iv) any combination of (1) to (iii). 98.  For example, the apparatus of claim 95 includes a component 收集 collector operatively adapted to, responsive to, a change in the combined signal to collect a new sample component. 9 9. The apparatus of claim 91, the apparatus comprising (1) a chromatography column, (ii) two or more non-destructive detectors, and no destructive detector in the system, and (iii) a component collector in fluid communication with the two or more non-destructive detectors. 100.  The apparatus of claim 94, the apparatus comprising a shunt pump φ or a shuttle valve positioned to be in fluid communication with the at least one detector and actively controlling fluid flow to the at least one detector . 101.  An apparatus for analyzing an apparatus comprising: (a) a component collector in a liquid chromatography system, the component collector being operatively adapted to be adapted to receive, receive, and process from at least one One or more signals of the detector, and one or more sample components are collected based on the one or more signals. 102. The device of any one of claims 52 to 101, wherein the device comprises at least one detector selected from the group consisting of at least one ultraviolet detector, at least one evaporative light scattering detection Detector (ELSD), at least one mass spectrometer (MS), at least one condensed nucleation light scattering detector (CNLSD), at least one corona discharge detector (CDD), at least one refractive index detector (RID) At least one fluorescent detector (FD), at least one chiral detector (CD), or any combination thereof. 103.  - A method of analyzing the same method using chromatography, the method comprising the steps of: (a) observing the sample comprising at least one non-colour-bearing test compound using at least one detector; and (b) reacting a detector In response to a change in one of the non-chromophoric compounds, a new sample component is collected in a component collector. 104.  The method of claim 103, wherein the sample consists of a non-carrier mobile phase. 105.  An apparatus for analyzing a fluid sample using chromatography, the apparatus comprising: φ (a) at least one detector capable of detecting a color-bearing and non-carrier-test compound in the sample; and (b) - a component collector capable of reacting to a change in one of the non-carrier compounds in a detector reaction. 106.  The apparatus of claim 1, wherein the sample consists of a non-carrier mobile phase. 107.  A method of analyzing a fluid sample using chromatography, the method comprising the steps of: -85- 201022666 (a) providing a first fluid; (b) using a shuttle valve to remove an integral point from the first fluid a fluid sample that does not substantially affect the flow characteristics of the first fluid; (c) using at least one detector to observe the fluid sample; and (d) a change in the reaction-detector response from The first fluid collects a new sample component in a component collector. 10 8. The method of claim 107, wherein the first fluid flow through the shuttle valve is substantially laminar. 109.  The method of claim 107, wherein the first fluid pressure system passing through the shuttle valve does not substantially increase or substantially maintain a constant temperature.  The method of claim 107, wherein the method includes a second fluid to transport the whole fluid sample to the detector. 111.  The method of claim 107, wherein the second fluid flow through the shuttle valve is substantially laminar. 112.  The method of claim 107, wherein the second fluid pressure system is substantially not increased or substantially maintained by the shuttle valve. 113.  An apparatus for analyzing a fluid sample using chromatography, the apparatus comprising: (a) a first fluid path; (b) at least one detector capable of analyzing the fluid sample; and (c) a shuttle valve An aliquot of the fluid sample is transported from the first fluid path to the detector without substantially affecting the fluid properties of the fluid passing through the first fluid path. 1 14. The apparatus of claim 113, wherein the at least a portion of the first fluid path through the valve is substantially linear or straight. 115. The apparatus of claim 113, wherein the fluid pressure system passing through the first fluid path does not substantially increase or substantially maintain a constant. I 16. The apparatus of claim 113, wherein the apparatus includes a second fluid path, the whole fluid sample is transported to the detector, 117. The apparatus of claim 116, wherein at least a portion of the second fluid path through the valve is substantially linear or straight. Reference II 8. The apparatus of claim 116, wherein the fluid pressure system passing through the second fluid path does not substantially increase or substantially maintain a constant. 119.  The apparatus of claim 113, wherein the apparatus includes a plurality of dimples such that the first fluid path is substantially parallel to the dimple. 120.  - Apparatus for analyzing a fluid sample using chromatography, the apparatus comprising: U) - a first fluid path;  (b) a second fluid path; (c) at least one detector capable of analyzing the sample; and (d) a shuttle valve for transporting an entire sample from the first fluid path to the second fluid The path, while maintaining a continuous second fluid path through one of the shuttle valves. 12 1. The apparatus of claim 120, wherein the fluid pressure in the first fluid path and/or the second fluid path through the shuttle valve is substantially not increased and/or substantially maintained. -87- 201022666 1 2 2. The apparatus of claim 120, wherein the apparatus includes a plurality of dimples such that the first fluid path is substantially parallel to the dimple. 123. A method of analyzing a fluid sample using chromatography, the method comprising the steps of: U) providing a first fluid flowing from a chromatography column; (b) providing a second fluid, the fluid sample Served to at least one detector; reference (c) using a shuttle valve to move a aliquot of sample from the first fluid to the second fluid while maintaining a continuous path of the second fluid through the shuttle valve; (d) using at least one detector to observe the aliquot; and (e) reacting one of the detector responses to collect a new sample component from the first fluid in a component collector. 124.  The method of claim 123, wherein when the aliquot Q is removed from the first fluid and transported to the second fluid, the first fluid passes through a continuous flow path of the shuttle valve and remains . 125.  The method of claim 123, wherein the first and second fluids pass through the continuous flow path of the shuttle valve when the aliquot is removed from the first fluid and transported to the second fluid Will be maintained. 126.  A method of analyzing a fluid sample using chromatography, the method comprising the steps of: (a) providing a stream comprising one of the samples; -88 - 201022666 (b) using a general carrier fluid 'moving away from the stream And (c) using at least one detector to analyze the integral portion of the universal carrier fluid, (d) wherein the universal carrier fluid comprises a gas or a liquid, which is miscible with the organic Solvent and water, low volatility, and non-carrier color. 127.  The method of claim 126, wherein the carrier fluid comprises isopropanol, acetone, methanol, ethanol, propanol, butanol, isobutanol, stilbene, or a mixture thereof. 128.  The method of claim 126, wherein the carrier fluid comprises isopropyl alcohol. 129.  - A device for analyzing a fluid sample using flash chromatography, the device comprising '· (a) - an evaporative particle detector 'which is capable of detecting individual compounds in the sample; and φ (b) - component collection A device capable of reacting to a change in one of the detector responses to the 'detected compound', (c) wherein the evaporative particle detector is the only detector in the device. 130.  An apparatus as claimed in claim 129, wherein the evaporative particle detector is capable of detecting chemical composition, chemical structure, molecular weight, or a combination thereof. 131. The apparatus of claim 129, wherein the evaporative particle detector-89-201022666 detector comprises an evaporative light scattering detector, a condensed nucleation light scattering detector, or a mass spectrometer. 132. - A method of analyzing a fluid sample using flash chromatography, the method comprising the steps of: (a) observing the sample using an evaporative particle detector capable of detecting a respective compound; and (b) reacting about A change in the detector response of the compound collects a new sample component in a component collector, (c) wherein the evaporative particle detector is the only detector used to analyze the sample. 13 3. The method of claim 132, wherein the evaporative particle detector is capable of detecting chemical composition, chemical structure, molecular weight, or a combination thereof. 134. The method of claim 132, wherein the evaporative particle detector comprises an evaporative light scattering detector, a condensed nucleation light scattering detector, .  Or mass spectrometer. -90-
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