TW539856B - Electrospray device for a mass spectrometer and method of delivering a plurality of sample streams to a mass spectrometer for sequential analysis - Google Patents

Electrospray device for a mass spectrometer and method of delivering a plurality of sample streams to a mass spectrometer for sequential analysis Download PDF

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Publication number
TW539856B
TW539856B TW088104829A TW88104829A TW539856B TW 539856 B TW539856 B TW 539856B TW 088104829 A TW088104829 A TW 088104829A TW 88104829 A TW88104829 A TW 88104829A TW 539856 B TW539856 B TW 539856B
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Taiwan
Prior art keywords
electrospray
needle
scope
mass spectrometer
item
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TW088104829A
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English (en)
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Ole Hindsgaul
David C Schriemer
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Synsorb Biotech Inc
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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph
    • G01N30/724—Nebulising, aerosol formation or ionisation
    • G01N30/7266—Nebulising, aerosol formation or ionisation by electric field, e.g. electrospray
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
    • G01N33/537—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody
    • G01N33/538—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody by sorbent column, particles or resin strip, i.e. sorbent materials
    • G—PHYSICS
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    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54306—Solid-phase reaction mechanisms
    • G—PHYSICS
    • G01—MEASURING; TESTING
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    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
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    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J2219/00704—Processes involving means for analysing and characterising the products integrated with the reactor apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
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    • B01J2219/00702—Processes involving means for analysing and characterising the products
    • B01J2219/00707—Processes involving means for analysing and characterising the products separated from the reactor apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00731—Saccharides
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    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00738—Organic catalysts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/00745—Inorganic compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/00745—Inorganic compounds
    • B01J2219/00747—Catalysts
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B30/00—Methods of screening libraries
    • C40B30/08—Methods of screening libraries by measuring catalytic activity
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/12—Libraries containing saccharides or polysaccharides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/18—Libraries containing only inorganic compounds or inorganic materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N2030/628—Multiplexing, i.e. several columns sharing a single detector
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/84—Preparation of the fraction to be distributed
    • G01N2030/8429—Preparation of the fraction to be distributed adding modificating material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/84—Preparation of the fraction to be distributed
    • G01N2030/8447—Nebulising, aerosol formation or ionisation
    • G01N2030/847—Nebulising, aerosol formation or ionisation by pneumatic means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/38—Flow patterns
    • G01N30/46—Flow patterns using more than one column
    • G01N30/466—Flow patterns using more than one column with separation columns in parallel
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
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    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
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    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
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Description

539856 A7
本申請文件為 U.S. Serial NO. 09/069,656, filed Apdl Μ 1998 之績編’它聲明出 u.s. provisi〇nai ApplieatiQn N。 60/079,622，filed March 27，1998 中之優點，這些申請文 件，每一條都納入本文中，並全部作參考之用。 1明背景 發明領域 本發明係有關液體輸送裝置，以及較特別地，本發明係 有關輸送多種流體樣品流至一質譜儀，以分析出化合物實 驗成份（libraries)之裝置。 相關技術之簡述 在最近幾年，發展出大量的合成化學技術，使得很多種 類的化學成分能很快地合成出來。在合成化學物質之過程 中，會產生一連串之化學反應，特別是每一個步驟中都會 使用到多種試劑，以產生一些化合物之實驗成份，像這二 技術，已使得新化合物的發現速度大為增加，由於這些新 化合物可提供生化篩選技術上所使用之多種化學成份，因 此，具備著有用之生化特性。 而質譜儀的出現，成為檢視合成物質實驗成份之一項重 要工具，直至今日，質譜儀已被用來評估實驗成份數量， 以及，田與匀子量鏗定技術（m〇lecular re⑺糾ition technology)配合使用時，可成功地分離出並判定出有作用 化合物實驗成份之特性，在合成化學及生化研究之領域 上，有關質譜儀之申請文件也變得愈加重要。 將分子離子化，測量出它們的飛行時間（time_〇f-flight), -4-本紙張尺度適用中國國家標準(CNS) A4規格(21〇 X 297公嫠) 539856 A7 B7 五、發明説明（2 ) 或是測量在電場以及/或磁場中，分子軌道之反應，質譜儀 便可得出化合物之分子量以及結構上之資料。電噴霧過程 則是最有可能可使一個範圍内之分子，產生氣相離子之技 術中之一。
裝 大數量樣品之分析，就愈加依賴質譜儀，特別是像辨識 蛋白物質之生化序列，就需要大量色譜分析之質子光譜曲 線圖，例如，像是SDS-PAGE(十二烷鈉聚丙烯硫酸凝膠電 泳法 sodium docecyl sulfatepolyacrylamide gel electrophoresis) 的二度空間的電泳分離法，就可從細胞粹取中，分離出數 千種的蛋白質，而在此的每一個分析，都須要用到質子光 譜特性圖。 鬌 依照傳統之電噴霧過程，其中含有我們所想要分子之一 樣品溶液，以及一適當之溶劑，會抽取入或經由電喷霧針 頭之吸取，而進入電噴霧室中，而高達數千伏特之電壓會 施加在針頭上，以產生帶電的細微霧滴。相反地，針頭也 可以接地，並且將溶液噴入一外加之電場中，特別是霧滴 會在大氣壓力下喷入喷霧室中，或者，在噴霧室中選擇使 用標準氣體（gas line，例如像氮氣），以幫助溶液之氣化以 及溶液之分解或蒸發，以電噴霧過程產生出之離子，會在 適當的電場梯度下被導入質譜儀中，特別是，這需要多次 的抽取過程，以除去像是溶液蒸氣之多餘電中性。 在傳統的電噴霧裝置中，電噴霧針頭是連接在一單一的 流體樣品（sample stream)上，並經由電喷霧過程將内含的分 子輸送至分析用之質譜儀上。而當須製備多種流體樣品 -5- 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐) 539856 五 、發明説明（ 接續下—種流體樣品就相當費時，這是譜有單-電噴霧針頭。因此，樣品以 必須再重建盥一 斷而 夺”下種泥姐樣品之連接。撇開流體樣品接續 ^ 1〈時間問題不提，也會出現不同流體樣 叉污染。 4 < 、因此’要作到能夠使多種流體樣品’由色譜柱 源頭處’輕易地連接至質譜儀之電噴霧裝置，並可由多 圖:中作出週期性之流體樣品分析，也儘可能地作到， j最短的時間内’由一種流體樣品之分析，自動地移至另 一流體樣品以至於多種流體樣品之分析。 發明掏要 本發明係有㈣，利用所裝設之多個電噴霧針頭，依序 輸送多種流體樣品流至-分析用質譜儀之電喷霧裝置。 依照本發明（-觀點，質譜儀之一電喷霧裝置包含一 喷霧室，裝設在支撐面板上大致成圓形排列之多個針頭 -可旋轉7C件’以及-充電器。電噴霧針頭可與多種流 樣品連接，並可輸送流體樣品之霧滴流至一質譜儀之 洞；可旋轉之元件可旋轉並將其中—種流體樣品之霧滴 次導至質譜儀之孔洞中；充電器則會施加電荷在電噴霧 中流體樣品之霧滴上，並使霧滴聚集成束以便經由孔洞 入質譜儀中。 依照本發明之另—觀點，提供—輸送多種流體樣品流至 —分析用質譜儀之方法’此方法所包含之步驟為，輸送多 交 品 種 能 電 體 孔 室 進 -6 五、發明説明（4 ) 種流體樣品流至裝設在支撐面柘 、 又？牙面板上又多個電喷霧針頭·瓦 將流體樣品作連續喷霧之雷嗜靈4 、’了 …"r 霧針頭，·以及依序為位於輪 迗位置上爻電噴霧針頭提供一出 m 供出口，並在預定的停留時間 (dwell)内，旋轉並停下可於絲-μ 吁口 . 謂騎下了旋轉疋件，以便輸送 至質譜儀上。 银"成 圖形之簡t 現在可參考附帶說明圖形之更佳具體實例，來描述本發 明更進一步U田節ϋ參考其中具有數字之部份，以^ 其中： 圖1為輸送多種流體樣品流至一質譜儀之多針頭電喷霧 裝置側視圖； 圖2為圖1多針頭電噴霧裝置之俯視圖； 圖3為多針頭電喷霧裝置另一具體實例之俯視圖形； 圖4為成放射狀位置，非旋轉針頭之多針頭電嘴霧裝 置’另一具體實例之俯視圖形； 圖5為成成平行排列，非旋轉針頭之多針頭電嘴霧裝 置，另一具體實例之側視圖形； 圖6為依照本發明一實例之一離子色譜柱圖； 圖7為圖6離子色譜柱圖中一部份之放大圖；及 圖8為依照本發明之更進一步實驗之離子色譜柱圖。 元件符號說明 10 電噴霧針頭 16 樣品充電板 12 旋轉面板 18 色譜柱 14 電噴霧室 20 質譜儀 本紙張尺度適用中國國家標準(CNS) Α4規格(210X 297公釐) 539856 五、發明説明（ Π 8色譜柱 120質譜儀 210電噴霧針頭 212固定板 2 14阻擋元件 216 開口 2 1 8色譜柱 222質譜儀之入口孔洞 22質譜儀入口孔洞 24 通道 26 電極 3 6 驅動軸 3 8 混合丁座 40 底匣 110電噴霧針頭 112旋轉面板 之細節 一種用在質譜儀上之多咎 多針頭電噴霧裝置，包括 凡 旋轉面板12上，用以依总、、、 匕括裝自又在可 力丄 序/王入多種流體樣品之多個雷喑霖 針頭1〇。這個可旋轉之電噴霖以％ 夕個电噴漆 ^ ^ 包臂霧裝置，精由面板12旋轉至 另一針頭之前，持續一短车 ^時間依序監控來自於每-針頭的 ^姐樣印’以便在很短之時間，藉由_單—個質譜儀，使 可旋轉之電噴霧針頭裝置收集到來自於多種流體樣品之資 料。 師選實驗成份方法之實例，牽涉到如u s. patent Application Serial Ν〇· 〇9/〇7〇，131，”，μ%，以及 U.S. Patent Application Serial No.__，甚至於附加在 此並全文作為參考之隨函資料（委任備審文件編號 026579-251)中所描述到，以電噴霧質譜儀來分析多種流體 樣品。根據此方法之申請文件，要製備出像是合成化學技 術中之實驗成份。而多種流體樣品中之每一種，都包含有 先前經過多個色譜柱實驗之實驗成份或副實驗成份 -8 - 本紙張尺度適用中國國家標準(CNS) A4規格(210X297公爱） 539856 A7 B7
五、發明説明（6 (sublibrary)。每一種流體樣品，也經過單一之色譜柱實驗， 以便以圖形中之目標接受器（target recept〇r)分析出流體樣 品間之交互作用。色譜柱包括一可使目標接受器聯結上或 偶接上之固體支撐或内部材料。當流體樣品連續地注入並 通過色譜柱時，流體樣品中這些對目標接受器（例如配位體） 有較高親和力的成份，會與目標接受器有較強的結合力。 當色譜柱中的成份到達平衡時，這些具有最低親和力之成 伤，便會最先解體（break through)並經過色譜柱並到達柱 外，而存留於色譖柱中之流體樣品，會以電噴霧質譜儀加 以分析，以求出每一種成份之解體時間。由於，質譜儀在 此過程中，可同時查出並定義出存留於柱中流體樣品之實 驗成份，因此特別具有用途。 圖不於圖1是輸送多種液狀流體樣品流至質譜儀2〇電噴 霧裝置足第一個具體實例，電喷霧裝置包含一電喷霧室 14，它會使以電噴霧針頭1〇輸送之流體樣品霧滴帶電，並 將帶電離子成束地輸送至質譜儀2〇中。 每一個電噴霧針頭、〇,都具有一裝設在可旋轉面板12 上<上端（upper end)，並如圖2所示之俯視圖中成環狀排 列电嘴霧針頭之下端（l〇wer ends)可旋轉進入電喷霧室14 中^再次（reproducible)輸送位置，輸送位置精確地位於相 對於％潛儀20孔洞22之位置上，使霧滴可集中成束並通 過孔洞。輸送位置最好是大約±〇·5公釐内之理想位置。如 ，圖π於圖1之色譜柱18，與每一個電噴霧針頭1〇之液 感連接’就是樣品源。色譜柱最好是裝設在可旋轉面板i 2
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之了:崎，或是以彎線與針頭1 〇作連接。 繞在質譜儀孔洞22周圍之電噴霧室14，係開放於大 截i 力 ~F* 〇 Ά 一 。為了達到包圍的目的，電喷霧室1 4則圍繞在針 頭10之周圖 士 、 .‘』圍’ /、有一個靠近於輸送位置上之針頭1〇會處 "鬲之黾场下，並將氣相離子有效地傳送至質譜儀2 0 中〇 减私2霧針頭10最好是同軸（coaxial)之針頭，它可輸送流 &樣使其通過針管内腔，並輸送像是氮氣之霧狀氣體， 同軸地％繞流體樣品，使流體樣品分解成霧滴。或者，針 顽10也可以是只輸送流體樣品之單一針管。電噴霧室Μ 包括包圍在質譜儀入口孔洞22處之一樣品充電板16，電 喷霧室14也可包括成半圓柱體元件之電極26。樣品充電 板16及半圓柱體電極26最好在〇至6〇〇〇伏特之電壓下加 以无電，以樣品充電板16及電極26所建立出之電場，環 繞在接地針頭1 〇之周圍，並且會對霧滴充電。 —依照本發明之另一具體實例，存留於電噴霧針頭1 〇内流 體樣品霧滴之充電，可藉由使用充電過之電噴霧針頭，一 偏壓樣品面板16，以及不用到電極26來達成。針頭1〇可 以作連續性之充電，或者只有在以電性接觸方法，而使針 頭到達電噴霧室14中之輸送位置上時，才作充電。 像是氮氣之逆流（counter current)乾燥氣體，會經由樣品 充電板16與入口孔洞22間之通道24,輸送入電噴霧室二 中’以助於流體樣品分解或蒸發成細微霧滴。根據本發明 之另一具體實例，乾燥氣體可以以不需經過通道24之方 -10 -
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法，而輸送至電嘴霧室14中。除此之外，霧氣可以不是同 ^(co-axml·)流經，而是分別地經由電噴霧針頭輸送至電喷 療i 14中務氣及乾燥氣體，兩者都可導入於電噴霧室 ^中、，以形成流體樣品之細微霧滴。無論如何，依流體樣 口口之流速而走也可以不需要霧氣和/或乾燥氣體，就可形 成細小之霧滴。
旋轉面板12藉由一馬達之旋轉，而連接至面板上之一驅 動軸36。馬達最好以—控制器作界面控制，以控制面板之 旋轉以及每-個針頭之停留時間。雖然所舉出之旋轉面板 12是-圓形面板’但必須了解的是，面板也可以是其他形 裝 :恭像是多邊形面板、環狀、以及，也可以是不至於偏離 本發明太多之其他形狀。 ij 4 k 射ϊΓ乍二多Γ流體樣品市樣品源’以舉例而言像是注 射幫浦，連~地輸送至每—個色譜柱18中 =中二體ΛΓ也可以在位於柱與針頭10之間：混 口至或此口 T座38上，與稀釋液結合。 態連續地經由電喷霧針頭…至流體::二= 使液=成霧滴。最好是’在同時經過所有二園1〇 = 置上之其中-種樣品加以分析。“：：： =輸送位 針頭10，會經由一底匣（tray)40作擇L、則迗位置上之 則無用而排出。 乍選擇性〈收集，其餘的 在作多種流體樣品之分析時，本發 — 出’旋轉面板、2是以同一方向，例J :具體實例提 了矸万向作旋轉，
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至通過大約戶斤有針5員10之+ 。當使用-四極 (㈣卿_)質譜儀時，每―個電嘴霧針頭ig之停留時間， 1大約由0_5至10秒’在切換至下一個色譜柱之前，最 至5心。在分析過大約半數之流體樣品後，旋轉面 板12會順時針轉回起始位置，並以相反方向，例如順時針 万向作旋轉’而完成㈣之半數針頭1G。最後，旋轉面板 12曰再回到起始位置，並重覆此程序。此系統會依據色譜 柱設備而預先調整出運作週期，並連續地運作著。旋轉接 續針頭（間之接替時間（step times)，最好低於大約⑽毫 秒’不超過大約10毫秒則會更好。由面板12作同一方向 二旋轉並隨後相反方向之旋轉，可以避免由幫浦將流體樣 P口輸送至柱中之送樣線（feed lines)變形扭曲。
裝 η 4 k 根據本發明之[具體實例，流體樣品，幫浦，或者兩 者中之 以及用來流體樣品輸送至柱18中之送樣線，都 可以裝設在面板12上。在這樣的具體實例下，面板12可 以連續地作同一方向之旋轉，以依序對由每一針頭所流出 t樣品作分析，而不需作反方向旋轉並回到起始位置。 本發明所使用之質譜儀，可以是我們所知，包括四極質 譜儀，四極離子底匣質譜儀，Penning或paul離子底匣質 譜儀’傅立葉轉換感應偶合共振（FTICR)質譜儀，飛行時間 式質譜儀，或是類似之質譜儀中之任一種。由於飛行時間 式質If儀之光請取得速率較高（每秒所取得之光譜大於1〇〇 種），因此較佳，無論如何，也可以使用記錄光譜之速率每 秒大約〇·5至1秒之較慢四極質譜儀。分析每一種流體樣 -12- 本紙張尺度適用中國國家標準(CNS) A4規格(210X297公釐) 539856
亍則，所使用質譜儀之光譜取得而定。 置，其四極質議儀Λ使用具有10種色譜柱之電喷霧裝 時間約為每-是每秒-種光譜，以及停留 譜柱上可取得大約秒時，則此設備-次在每-種色 大約需60秒。 切，並且’作完全部之色譜柱則 本發明之另一且蛐眷 ^隨實例，也可以包括，依所要流 體樣品數目，而有；、办m/r罟刀析之泥 頭10之間之間距，在泰嗜靈世裘、访 包1務玎 ^ 在私噴硌裝置足掭作上是相當重要的， =:電噴霧針頭1〇間要有足夠之間距，以避免-個色 口曰…之泥體樣品’對相鄰色譜柱中流體樣品之分析所造 成之叉互效應。除此之外，電喷霧針頭1G間之距離，也要 接近到可足以使旋轉相鄰針頭之接替時間能降至最低。依
所使用 <質譜儀，色譜柱之間距必須大約有〇·5公分至W 公分，或者，也可以使用物理阻擋元件，以避免交叉效應， 以及使針頭位置儘量靠近。 圖3是用來將流體樣品輸送流至質譜儀12〇之可旋轉式 電噴霧裝置，另一具體實例之俯視圖。電嘴霧裝置包括， 裝設在旋轉面板12上，成放射狀排列之多個電噴霧針頭 110，每一個針頭都與色譜柱118作液態連接。電噴霧針頭 110之放射狀排列，可以讓較多之色譜柱118，以較小之半 徑裝在旋轉面板112上。根據本具體實例，針頭11〇之放 電端最好要有足夠之距離，以避免相鄰針頭間之交又效 -13-
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應。典論如何’色譜柱11 8要夠接近以便能環繞在旋轉面 板112之周·圍。 =4所不疋用來將多種液態之流體樣品，輸送流至一單 負w儀之私噴霧裝置之另一具體實例。圖4之電噴霧裝 置包括’裝設在固定板212或其他種支撐結構上，成放射 狀排列 < 多個電噴霧針頭210，每一個針頭210都與色譜 枉11 8或另一樣品源作液態連接。一内部之可旋轉阻擋環 或圓柱體214 ’則位於針頭21〇之出口與質譜儀之入口孔 洞222之間。阻擋元件2丨4裝設在一驅動軸上，並以一馬 達（圖中沒有畫出）作旋轉。阻擋元件214包括，可使氣相 離子傳运進入質譜儀中之一開槽或開口 216，可旋轉之阻 w 一牛 4也了以疋質羅儀離子透鏡（i〇n 〇ptics)之一部份。 圖^所示，是用來將多種液態之流體樣品輸送流至一單 質碭儀裝置，更進一步之另一具體實例。圖5之具體實 例不同於圖4 ,在面板上212針頭21〇之排列成圓形，大 體上，針頭之排列為彼此平行。如圖S所圖示，色譜柱218 可以裝设在固定板212上，或者也可以以連接線連接到針 員210上如圖5所示，包圍住質譜儀之入口孔洞222之 可旋轉阻擋元彳214,可以是一圓柱體元件，並且包 使氣相離子由其中一個針頭，一次傳送進入入口孔洞之一 開口 216。可旋轉之圓柱體214，經由一馬達帶動一驅I 224來作旋轉。 切袖 在圖4與圖5之具體實例中，針頭21〇之放電端之玲 好要間隔足夠之距離，以避免如上述相鄰針頭間之交又： -14-
本紙張尺度適用中國國家標準(CNS) A4規格(210X297公袭:) 539856 A7
應。阻擋元件214停留在每個針頭 、+加# 貝仏置上之時間，如上所 述，根據圖1及圖2之具體實例，仕、山± ^ ® 4 ^ ^ 依端賴所使用之質譜儀。 圓4及圖5义多針頭電噴霧裝置 ★朴$、皮 罝優於圖1至圖3旋轉形 式針頭芡優點，在於流體樣品之 旋轉及㈣扭曲。 在㈣過程中 旋轉式或非旋轉式支撑…2，112,212之方向及排 色瑨柱18 , 118,218以及電噴霧針頭10, 110,210, 可乂夂化出.午多不同《角度關係、，而與不同類型之質譜儀 配合使用。例如，旋轉面板可以成垂直位置，並且色譜柱 及針可以成水平位置。！^此之外，在—些類型之質譜儀 中，電噴霧室並沒有以外壁關閉起來。 比起前述一次操作及篩選一個色譜柱之技術，本發明物 提供了距離上之優點。可旋轉之電喷霧裝置，可以讓多種 流體樣品輕易地輸送流至一單一質譜儀中，並且在以一單 一質瑨儀對流體樣品作同步之色譜柱操作時，可以快速地 重覆分析動作。 範例 · 根據圖3之具體實例，將針頭成放射狀地排列在一旋轉 面板12或葉片上’架構起一四針頭之多噴霧裝置，在此所 描述的，是成垂直方向地組裝於樣品面板之前，並且四隻 針頭彼此成90度放置。如同此裝置所示範，選出一單一針 頭’並與含有以1: 1之氰化甲烷：緩衝液（pH值7.2之2 mM 乙酸铵）’調製出10 μΜ之衍生三醣（derivatized trisaccharide 681.2 u之m/z)溶液，而不分析其他之樣品。 -15- 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐) 539856 A7
在選擇離子監控模式時，係使用一 Hewlett_packard系列之 1100MSD電噴霧質譜儀（四極），而與流體樣品（1〇 pL/min) 連接之針#員，位於樣品孔洞之前方，使離子傳送度能到達 取大，並且可選用質譜儀之條件，以監控此成份。使用可 以作到每次運轉200步進（steps)，且停留時間為1〇秒之步 進馬達，則組裝之針頭便可以在每秒5〇〇步進之固定速率 下，旋轉90度。這樣的運轉，可以使電噴霧針頭擺動至最 佳位置上，在1 〇秒結束後，電噴霧針頭會倒退擺動度。 圖6圖示出此實驗所得出之離子色譜柱圖形，當流體樣品 與多電噴霧針頭連接上，只有當步進馬達將流體樣品轉回 位於樣品孔洞前方之原處，才會看得到信號，要注意整個 信號在五個循環過程中是相當快速而重覆地。所顯示出圖 6色譜柱圖形放大之圖7 ,可看出快速的上升時間（小於的 ms)，此實驗表現出四極質譜儀之.最大速率樣品。 在更進一步之範例，實驗中在樣品孔洞前方之停留時 間，由3秒轉變成〇.5秒，而步進馬達的速率仍固定:每 秒500步進，所得出之色譜柱圖形圖示於圖8中。在每一 個例子中，上升時間都小於60 ms,而信號也都能完全地 恢復至原狀（要注意色譜柱圖形中之任一峰值所反映出的 是嘴霧的一般不穩定狀況而不是多電噴霧針頭之本身性 能）。圖8中建議，在相當高之質譜儀樣品速率下（例如 TOF)，應該會得到較短之上升時間及較短之停留時間。 根據參考其中較佳具體實例之細節所描述出之本發明， 可以很明顯地看出，在不至於偏離本發明太遠之前提下， -16 -
裝 訂
539856 A7 B7 五、發明説明（14 ) 同之設備，則可以達 經過不同之改變及修正，以及使用不 成一種技術。 -17- 本紙張尺度適用中國園家標準(CNS) A4規格(210X 297公釐)

Claims (1)

  1. 539856 申請專利範圍 A8 B8 C8 D8
    1· 一質譖儀用之電噴霧裝置，包括： 斜Γί:支撐面板上’依序成圓形排列之多個電噴露 針頭，電噴霧針頭可與多種流 彡個电噴療 體樣品之液滴流至一質譜儀之孔洞’以便輸送流 旋轉元件，用來引導其中二種流體樣品之液、、自一 次流至一質譜儀之孔洞；以及 <履，同一 一可將電荷施加在流體樣品液 聚集成束，以通過„儀之孔洞^无^，並使離子 2,；據申請專利範圍第1項之電嘴霧裝置，其中針頭裝投 於一可旋轉之針頭支撐面板。 針M裝汉 3·根據中請專利範圍第2項之電嘴霧裝置，其中可之 =擇面板為一可旋轉之圓盤，並裝設有針頭中心軸 依序成平行之多個電喷霧針頭。 4·根據中凊專利範圍第2項之電嘴霧裝置，其中可旋轉之 =員支撐面板為-可旋轉之圓盤，並裝設有.針頭成放射 狀排列之多個電噴霧針頭。 經濟部中央標準局員工消費合作社印策 其中多個電1 以及可輸送| 其中多個電1 (請先閲讀背面之注意事項再填寫本頁) 根據申叫專利範圍第1項之電嘴霧裝置 霧針頭為，具有可輸送流體樣品之内腔 狀氣體之外腔之同軸針頭。 6·根據申請專利範圍第i項之電噴霧裝置… 霧針頭為，可輸送流體樣品之單一管腔針頭。 7·根據申請專利範圍第i項之電噴霧裝置，其中充電器 括位於電噴霧室内，依序圍繞在質譜儀之孔洞周圍 —帶電樣品面板，以及接地之電噴霧針頭。
    539856 申请專利範圍 8.根據申請專利範圍第i項之電喷霧裝置，其中 :頭Si— »源之連接，使其電性接觸可對St 乍无^，以及一偏壓樣品面板。 A 專利範圍第1項之電噴霧裝置，還包括裝設在 中二上《多個色譜柱，其中，每-個色譜柱均與其 針頭作液態連接，以便輸送存留於色譜柱中之流 像p口流至質譜儀中。 10.H中請專利範圍第9項之電喷霧裝置，還包括裝設在 並與多個色譜柱連接之一樣品源，其中一 』:可使針頭支撐面板作單—方向之旋轉，以分析來 自於電嘴霧針頭之流體樣品。 .:據申5B專利範圍第i項之電喷霧裝置，還包括以液熊 連接線連接上電嘴霧針頭之多個色譜柱。 ^ .根據申吨專利範圍第i項之電噴霧 :住並包圍住針頭之，霧室圍繞著其h喷霧針 .=申^專利範圍第1項之電噴霧裳置，另包括一可使 it件:婦之馬達，以及可使旋轉元件作旋轉2 ;。使母-個電嘴霧針頭都可達到-固定之停留時 14.根據申請專利範圍第2項之 可使針頭支撐面板作第—種方其中“以 將近半數針頭之流 ^向《旋轉’以分析來自於 二種方向之旋m二使針頭支撐面板作第 流體樣品 ^來自於㈣餘料半數針頭之 -19 本纸張尺度相_雜準(⑽）A4規格(21〇; 公釐) 539856
    申請專利範圍 A BCD 5·根據申請專利範圍第1項之電噴霧裝 杜、a u 衣夏，其中可旋轉元 件為-可旋轉之阻擋元件’它具有可輪送其中一種樣品 〇從滴’一次流至質譜儀孔洞之開口。 根據申請專利範圍第丨5項之電噴霧 阻擒疋件為，具有旋轉軸依序與質譜儀孔洞排列成 線之可旋轉圓柱體。 17·根據申請專利範圍第15項之電噴霧裝置，其中多個 霧針頭是裝設在面板上之固定位置， 私— 久可旋轉义阻 搞几件疋位於多個質譜儀之間。 18·種輸运多種流體樣品流至一質譜儀以依序作分析之方 法，此方法包括： 提供多種流體樣品至裝設在支撐面板上之多個電噴霧 針頭中； 以電噴霧針頭連續地噴出流體樣品；以及 在預疋<停留時間下，以旋轉並停下可旋轉元件之方 法，依序為每個位於輸送位置上之電噴霧針頭提供一出 口 ’以輸送流體樣品流至質譜儀中。 19·根據申請專利範圍第18項之方法，其中預定之停留時間 低於大約5秒。 20.，據申請專利範圍第18項之方法，其中可旋轉元件可作 罘一種方向之旋轉，以依序輸送多種流體樣品流至質譜 儀中及面板上，然後，作第二種方向之旋轉。 21·根據申請專利範圍第18項之方法，其中電噴霧針頭並不 在輸送流體樣品流至一收集底匣之輸送位置上。 -20- 本紙張尺度適用中國國家賴CNS) Μ規格(勝撕公董)- 8 8 8 8 A BCD 539856 六、申請專利範圍 22. 根據申請專利範圍第1 8項之方法，其中依序在一輸送位 置上提供一出口之步騾，係由旋轉針頭之支撐面板來完 成。 23. 根據申請專利範圍第1 8項之方法，其中依序在一輸送位 置上提供一出口之步驟，係由維持針頭不動，並旋轉具 有開口之阻擋元件形式之可旋轉元件來完成。 -21 - 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐)
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