TW297094B - - Google Patents

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TW297094B
TW297094B TW082109320A TW82109320A TW297094B TW 297094 B TW297094 B TW 297094B TW 082109320 A TW082109320 A TW 082109320A TW 82109320 A TW82109320 A TW 82109320A TW 297094 B TW297094 B TW 297094B
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density
test tube
antibody
antigen
specific
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TW082109320A
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Levine Robert A
Wardlaw Stephen C
Becton Dickinson Co
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5021—Test tubes specially adapted for centrifugation purposes
    • 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
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G01N33/491—Blood by separating the blood components
    • 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
    • G01N33/5375—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody by changing the physical or chemical properties of the medium or immunochemicals, e.g. temperature, density, pH, partitioning
    • 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
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • G01N33/56972—White blood cells
    • 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
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/585—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with a particulate label, e.g. coloured latex
    • 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • 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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    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/81—Packaged device or kit
    • 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
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/967—Standards, controls, materials, e.g. validation studies, buffer systems
    • 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
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/971—Capture of complex after antigen-antibody reaction
    • 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
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/973—Simultaneous determination of more than one analyte
    • 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
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/805—Optical property
    • 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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    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/807—Apparatus included in process claim, e.g. physical support structures
    • Y10S436/81—Tube, bottle, or dipstick
    • 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
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/824—Immunological separation techniques
    • 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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    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/829—Liposomes, e.g. encapsulation
    • 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
    • Y10T436/11—Automated chemical analysis
    • Y10T436/111666—Utilizing a centrifuge or compartmented rotor

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
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  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
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  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Medicinal Chemistry (AREA)
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  • Biochemistry (AREA)
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  • Microbiology (AREA)
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  • Tropical Medicine & Parasitology (AREA)
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  • Biophysics (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)

Description

經濟部中央標準局8工消費合作社印製 A6 _ _B6_ 一 五、發明説明（1 ) 發明範圍： 本發明係以單一步驟同時來檢定全血，血漿或血清檢體 中’是否有一種或多種結合生物性粒子之活性偶合體之配 體成份，且本發明並可視需要進行定量檢定。 發明背景： 分析血液檢體中抗原或抗體之存在與否，可用來做某呰 疾病診斷，例如人類免疫不全病毒（HIV )感染、肝炎、 來姆症（Lyme disease)，產前締檢，包括TORCH (下列 名稱字頭姐成之單字，即毒漿體原蟲病，德國麻疹，巨噬 细胞病毒、疱疹）之篩檢，及其他感染性拷病之篩檢。現 行ώ清診斷多採標準間接螢光免疫檢定法。此法係先將可 抗原（其係待測抗體之偶合配體）固定在一固體材質上， 如玻璃片，紙膜或類似物。再將病人之血清檢體與該固定 之抗原接觸培養，其反應時間必須足Μ使配體抗體（如果 有的話）接附至該固定抗原。然後祌洗該撑體表面以除去 所有未結合之抗體。而後將含人類免疫球蛋白之標記抗體 之試劑再與撐體表面進行足夠時間培育，使該標記物質與 结合至固定抗原之病人抗體的任何痕量物相連接。再沖除 過量試劑並檢査撐體表面Μ鑑別是否有任何標記物存在。 Μ目测，分光比色測定法或螢光計量法來测定製備檢體。 值得注意的是，前述方法需經多重檢體處理步驟，包括冲 洗及分析技術*而造成大量勞力和時間之消耗。且前述步 驟僅能每次試驗偵測單一種特定抗原抗體存在與否，除非 做更進一步之測試，否則便無法區分特定之IgG或IgM ， 一 3 一 本紙張尺度適用中a國家標準（CNS)甲4規格（210 X 297公釐） (請先間讀背面之注意事項再塡寫本頁) .裝. 訂. A6 B6 經濟部中央標準局員工消費合作社印製 五、發明説明（2 ) 亦不能同時檢測多重抗原及/或抗體。 發明揭示： 1991年1〇月4日共同申請案USSN 07/770,875號揭示一 種K具有不同比重之微粒（以下稱密度標識物）形成各種 密度分佈帶區分紅血球計數之方法及裝置。本發明係關快 速而簡單檢定全血、血漿或血清檢體中，是否含有一種或 多種结合生物性粒子活性配偶體之配體成份的方法及設傲 。此可檢測之配偶體之賁例為TSH/抗TSH複合物，T4/抗 Τ 4複合物，德國痳疹抗體/抗德國麻疹抗體，人類免疫不 全病毒抗體/人類免疫不全病毒抗原。其中，T S Η ，Τ 4， 德國麻疹抗體及人類免疫不全病毒抗體為標的分析物。本 法係在離心管中執行且僅靠試管中含有數種試劑之血液檢 體加離心，再觀察離心步驟之结果。本鑑定可在豁生或技 術員完全不接觸血液檢體之情況下做成。 將含全血檢體置之試管離心，紅血球會在試管底部依其 密度形成不同之層次，密度最大之紅血球在底部。當血液 檢體在含有不同比重粒子群或微脂粒群而離心時，這些粒 子群或微脂粒群將在谁疊紅血球之各層間形成明顯可視的 標識環。離心試管中亦可含圓柱狀塑膠嵌入物固定於試管 、 _ . - t..…..·.·.，· — ' · I部，或於試管中自由移動，若該嵌入物可自由移動.，則 其比重讓該嵌入物能下沉至經離心血液檢體之紅血球層中 ° 之紅血球層 形成之標識環的距離拉長，且可迫使粒子群或微脂粒群至 試管的周邊而易於觀察，使其不致被紅血球所掩蓋。 -4- 本紙張尺度適用中國國家標準（CNS)甲4規格（210 X 297公釐） (請先間讀背面之注意事項再塡寫衣玎) 經濟部中央標準局員工消費合作社印製 A6 ___B6_ 五、發明説明（3 ) 在實施本發明中，粒子群或微脂粒群可偶合存在於病患 血液中之抗原或抗體，或其他互補之生物活性物質，或结 合配偶物（其可稱為"'標的分析物〃）。生物活性互補之 偶合Sa之實例包括：酵素及其受質，核脊酸及其互補核甘 ，源自天然之蛋白質結合物如甲狀腺结合球蛋白（TGB) 及甲狀腺素，“内在因子"和維生素B - 1 2，及S t ο 1 1 a r和 Rashtchian 在、、分析生物化學 a ，1987，161 ，387-394 中所提出、、Immunochemical Approaches to Gene Probe Assays 〃中所述用可選擇性偶合RNA-DNA雜種之特定抗體 〇 每一密度標識群都會包含一種與偶合粒子结合，而該粒 子可與血液或其他生物檢體中特定之標的分析物结合。將 檢體加入試管後，必須與密度標識物偶合粒子群充分混合 ，以便檢體中任何標的分析物可與密度標識物上之互補配 體偶合。 當使用本發明方法創造结合偶合物於偶合步驟完成後， 可產生一種已標記或附註之、''抗一抗原一抗體一複合物" 抗體（AAAC抗體）’其特定（亦可能在加入檢體前先加入 試管中）與密度標識物上之所有偶合體结合。此類AAAC抗 體可先乾燥塗覆於試管内壁，例如可以液態型式存在空試 管中如美國專利號碼5.086,784 ，所述。（Robert A. Levine 及 Stephen C. Wardlaw在 1992年 2 月 11 日獲得之專 利）。 此種抗體已由 Immunocytometry System Division of (請先閲讀背而之注意事項办填寫"頁) —裝· 訂- -5 - 本紙張尺度適用中國國家標準（CNS)甲4規格（210 X 297公釐） A6 經濟部中央標準局貝工消費合作社印製 B6 五、發明説明（4 ) Becton Dickinson and Company , of San Jose, California所製造。除對抗原/抗體偶合物有特異性外， 已附註之AAAC抗體亦可對免疫球蛋白亞群（如Igci或igM 抗體—抗原複合物）有特異性。同理，如待測物為R N A或 DNA ，則試管中應含有與RNA-DNA對有特異性標記抗體俾 與其结合，述於Stollar及Rashtchian。 該標記物可以用微脂粒包袤之著色劑，螢光著色劑或放 射性發散劑，此標記物必須可偵測，且最好可定量偵測。 已附註抗體將與所有密度標識物（具有偶合物）结合。離 心檢體Μ密度區分密度標識物而在試管中形成分離之帶狀 或環狀。而後檢査試管中不同密度標識帶是否含有可測得 之標記童，而且可能的話，測量標示量的多寡。常用的標 記物為螢光分子如FITC。 視需要，不同密度的珠子可Κ用不同顔色（若有一種Κ 上帶），不同顔色帶可用來鑑別不同之標的分析物。若使 用不同顔色的密度標識物|則某些試管中標記帶顔色會明 示结合分析物存於檢體中。若沒有分析物，則管中密度標 識帶不會鑑定任何有關標記物。如果有色密度標識物並未 被引用，則管中標記帶之位置可用Μ顯示分析物係在檢髏 中，或不在檢體中。這些資料當然可用來診斷檢體所有人 之健康。 因此，本發明提供一種分析生物性檢體之改良技術，Μ 決定其中是否有某些標的分析物存在。 本發明進一步目標係提供一種改良所述特性的技術，其 (請先閲讀背而之注意事碩再填寫衣頁) •'31. 一 6 — 泰紙張又度適用中國國家標準（CNS)甲y規格(210 X 297公釐） 第82109320IK専利申請案 Φ t 袒明窖 TF 苜 fat fe R Β7 五、發明説明（） vr 經濟部中央掭準局员工消費合作社印製 中Μ密度匾別法在透明檢體試管中進行分析。 '本發明更進一步目檷係提供一種改良所述特性的 其中以多種不同比重之珠子偁合至抗體及/或抗原 析使多種檢定可Κ同時在同一試管中進行。 本發明另一目檷係提供一種改良所述特性的技術 Μ形成醒目的抗《/抗原偁合帶來進行分析。 前述之其它欏的及優點將配合下列附鼷及由本發 較佳具體實施例之詳细描敘後•更明確顯示出來。 I示說明：；* ^ 匾1為迪用實腌本發明程序之《心試管之俩面上 圖2是經離心全血檢腰在圖1試管中之情況，其 球被放大來特別顯示本發明之特性。 圖3為適用實施本發明第二種具Μ實施例之離心 袖切面圖。 前述画中之代號於下文中說明。 最佳模式之詳细說明 參見圖1及圈2，圔1中，管>2〃係一玻璃毛畑管 它透明管，且係可含一浮《或塱膠嵌入物* 4 # · 物之比重f使其在全血檢《8鐮心時，穿越紅血球到 部6的位置。管2上糰塊5的位置可安置幾群偁合抗 或抗原之不同比重塑應小珠的配體基團（fraternal groups)。塑膠蓋子10接近管2之底部6。每一群塑 之比重都比最輕的紅血球（即最年輕的網狀血球）要 將血液檢嫌加入管2 ，在逋當培育時間後•輿嵌 技術· 進行分 ，其中 明下列 升釀。 中紅血 試管其 ，或其 該嵌入 管2底 «及/ 膠小珠 大。 入物4 -----1---.---j -裝----------訂-------{ ~ 線 (請先閲讀背面之注意事項再填寫本頁) 本紙張疋度適用中國國家標準（CNS)A4規格（210 X 29"7公釐） 83.3.10,000 經濟部中央標準局員工消費合作社印製 A6 _B6 _ 五、發明説明（6 ) 及塑膠小珠5 —起離心。該小珠圃塊在培苛期散佈於血液 檢體中，且在離心後移至紅血球層所形成明顯帶狀（如圖 2所示），浮體則移動與穿過紅血球R 。管2亦含有上述 附註之AAAC抗體。 白血球W會出琨在紅血球/白血球介面I之上面帶區。 密度標識小珠帶B依其密度分布在紅血球層中。檢査B帶 可明示B帶已被附註，原因是具螢光附鞋物只可在附註帶 中偵測到。 圖3是本發明中另一種型式之離心試管。管1 2為漏斗吠 ，上有寬闊開口末端部分1 4及限制封閉末端部份1 6。本試 管之口徑大小使血液檢體離心後，紅血球R沉人限制部分 1 6而白血球和血漿留在開口部分1 4。被附註的密度標識帶 B分佈在紅血球層中。管1 2係由透明玻璃或塑膠材質製成 。值得注意的是圖3中並沒有使用漂浮成份。 值得注意的是在圖2和圖3中，密度標識帶間之距離足 K進行蠻.光法或其它能量放射法且甚至可進行下述之定量 測定而不會受到其它B帶干擾。當全血檢體進行檢測時， 因紅血球在離心時有互相緊密结合排開血漿之特性，故要 確信所有未結合之標記A A AC抗體會停止於血漿層而不會干 擾程序。 本發明定量檢體中標的分析物使用之一般實例如下。翳 師由文獻中査明在一定量待測生物檢體中，有多少分子或 單位之標的分析物預期被檢測之近似範圍。例如* 一個被 感染或暴露在來姆症之病人預期每毫升血液中最多含50個 1------- I--— ---一 --------Λ*衣 -------S7 (請先閲讀背面之注意事項再.'«寫本頁) 一 8 — 本紙張尺度通用中國國家標準（CNS〉甲4規格（210 X 297公釐） A6 B6 經濟部中央標準局員工消費合作社印製 五、發明説明（7 ) 單位來姆分析物。貉師對每毫升血液檢體應至少加入100 單位密度標識/抗原/抗體偶合單元K及每毫升檢體加入 至少100單位已標記之AAAC抗體。因在檢體中有過量結合 位置及附註粒子相較於預期發現檢體中分析物單元之最大 數量，故由來姆珠子帶之標記放射強度量應與真正存在檢 體中來姆分析物數量成正比。因此，血液中來姆分析物之 定量，應可藉測得之放射強度定量近似計算出來。定量程 序的關鐽，在檢體中提供功能性過量之結合部位及附註抗 體以相較於預期出琨檢體中分析物單元之最大量。但是， 如果分析物的量與最後结合密度標識物AAAC抗體偶合體之 分析物其量間若存在有數學關係，則甚至在结合一* A A AC抗 體單元其存在莫耳量少於分析莫耳量下依然能定垦分析物 Ο 如果賁驗室想用血清、血漿檢體或須要其它更進一步預 測密度梯度，如不同密度之物質必須能夠互相分離，則圖 3所示管中狭窄之部分必須預先注入一穩定物質，如菲可 膠（Fico丨1 gel) ，Μ提供所需之密度梯度。此種密度梯 度的物質除了可將已有之帶分離外，亦可在離心的過程中 將未结合之AAAC抗體由結合層中冲洗掉。 須知悉，本發明雖然一直Μ血液診斷來說明，但本發明 亦可用於其他生物性體液中是杏有高特異性偶合體的診斷 。例如，Μ與全血性質不同的血漿來進行分析時，其離心 須於密度梯度流體（例如前述之菲可膠，來進行）此種物 質不會與水性相之生物性流體混合，而且在密度梯度流體 (請先閲讀背面之注芑事項再塡寫本頁) .裝· •11. -9 - 本紙張尺度適用中國國家捸準（CNS)甲4規格（210 X 297公釐） 297094
A6 BG 五、發明説明（8 ) 中可提供密度區分各帶，並且可沖洗密度標識物之梯度流 體*以確信由各帶中分離所有未結合標記物，Μ減少非結 合標記對定量標記帶產生之干擾。由於全血檢體測試時可 自動將來自標記细胞之未结合標記物沖洗掉，在利用菲可 膠對非细胞性流體進行檢定時係在離心期有冲洗之功能， 這項特性可省掉從前技術中須另有一沖洗步驟Μ防止未结 合標示物干擾實驗精確度。此項自動沖洗功能對本發明之 操作程序實有重大貢獻。 在不偏離本發明觀念下可由本發明揭示具體賁胞例導引 出許多變化與變異，並非用Μ限制本發明，而如申請專利 範圍所需。 (請先閲讀背面之注意事項再塡，Tct本1) 經濟部中央標準局員工消費合作社印製 -10- 本紙張尺度適用中國國家標準（CNS)甲4規格（210 X 297公釐）

Claims (1)

  1. 第82109320號専利申請案 中女由讅裒利鮪_tt7F太 A8 (84 钜 K 月）B8 C8 D8 公 表 申請專利範圍年 W3" 1 一種在透明試管中偵测生物性流《檢體中可疑檷的分析 其包括Μ下步》: ζ 物之方法* a) 在檢體 定之比重， 合，Μ形成 b) 加入已 c) 培育密 合物； d) 依密度 顯帶狀；及 e) 測量此 決定是否有 根據申謫專 檷識物群至 檢體中之一 檢»中之檷 檷識物均與 一種檷的分 一密度檷嫌 中加入一群密度 且該群中每一密 對可疑檷的分析 檷記偁合《结合 度檷識物/已檷 檷識物，該密度標識物具預 度檷雄物可與结合性物質偁 物特異之密度檷識偶合》; 性抗體至檢體中； 記偶合《I结合性抗體檢體混 聚集密度檷識物•在試管中形成至少一俚明 帶狀是 檷的分 利範圍 該檢體 或多種 的分析 他群之 析物有 物/结 否有已檷記偶合«结合性抗《存在而 析物存在。 第1項之 中而於該 方法，其 透明試管 不同檷的分析物* 物使用一群密度檷 比重不同 特異性之 合性物質 ,且每一 结合性物 偶合基團 係»加入不同密度 中偵測生物性流Η 每一種懷疑存在於 識物*每一群密度 群密度檷識物與對 質偁合•因此，每 均對不同之可疑檷 (請先間讀背面之注意事項再塡寫本頁) 經濟部中央標準局員工消费合作社印製 行檷 全 進已 是 在之 體 括合 檢 包结 體 步未 流 1 換 該 進置 中 其中 其 ，物 ， 法豳 法 方樣。方 之度驟之 項密步項 2由之 3 。第時《第 性圃驟抗圃 異範步性範 特利雕合利 有專分结專 物請分體請 析申區合申 分據度偶據 的根密記根 a4. 本紙張尺度適用中國國家標準（CNS)A4規格(210 X 25>7公釐） 六、申請專利範圍 血，且密度檷識物之比重大於最輕紅血球之比簠。 & 根據申請專利範圍第4項之方法，其中該置換步驟係離_ 心全血檢體之紅血球。 ^ 一種在透明試管中偵测生物性流«檢《中可疑檷的分析 物之方法，該試管含有一群與對可疑檷的分析物有特異 性之结合性物«偶合之密度檷識物，且該密度欏雄物具 預定之比重，而該試管含有已檷記之偁合《 —结合性抗 體，該方法包括以下步驟： 將檢體加至試管中； b) 於該試管中培育密度檷識物/偁合體一结合性抗《8 /檢體混合物； c) 依密度聚集密度檷雄物，在轼管中形成至少一個明 顧帶狀；及 测量此帶狀是否有已檷記偶合體一结合性抗體存在 -而決定是杏有檷的分析物存在。 7. —種κ離心分析生物性流體檢體中是否含有檷的分析物 之装置*該装置包括： a) —届透明試管，其具接受流《檢體之孔徑； 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再塡寫本頁) b) -*種在該試管孔徑中之嵌入物*其係固定在試管底 部，或可於試管孔徑中自由移動而其比重可使其於檢體 離心時沈降至試管底部； c) 位於該試管孔徑上部之密度檷雄物，該標識物為與 檷的分析物一特異性抗《及/或抗原偁合之具不同比重 之微粒或微脂粒； -2 - 本紙張尺度適用中國國家標準（CNS)A4规格（210 X 297公釐） A8B8C8D8 經濟部中央標準局员工消费合作社印製 六、申請專利範圍 _ d) 在試管孔徑中之可操作董巳檷記抗一抗原一抗體一 複合物（AAAC)抗體*該AAAC抗體對該密度檷識物上形 成之任何抗體/抗原/分析物偁合《有特異性·且可使 該偁合體被偵测出來；及 e) —種離心裝置，可使密度檷識物在該試管孔徑中依 密度分成相間隔之帶或環狀。 a —種Μ離心分析生物性流《檢體中是否含有檷的分析物 之裝置•該裝置包括： a) =儒透明試管•其具複·孔徑*開孔播德大 一 而末端换萝； b) 位於該孔徑膨大孀之密度檷雄物，該檷識物為與檷 的分析物一特異性抗«及/或抗原偁合之具不同比重之 微粒或微脂粒； c) 在試管孔徑中之可搡作量巳標記抗一抗原一抗« — 複合物（AAAC)抗箱·該AAAC抗《對該密度棟識物上形 成之任何抗雅/抗原/分析物偶合體有特異性，且可使 該偶合雅被偵測出來；及 d) —種雛心装置，可使密度檷讖物在該試管孔徑中依 密度分成相間隔之帶或環狀。 a 根據申請專利範園第7或8項之裝置，其中該試管中抗體 及/或抗原一偁合之密度標雄物以及已標記AAAC抗體之 量超過檢體中預期的棟的分析物單位之曇，以足以定量 檢體中檷的分析物。 ία 根據申請專利範園第9項之裝置，其中抗體及/或抗原 —3 — 本紙張尺度適用中國國家標準（CNS) Α4規_ (210 [297公寶) ----l·------裝---------订 11-----(Ί— 線 (請先閲讀背面之注意事項再塡寫本頁) 經濟部中央標準局貝工消费合作杜印製 A8 B8 C8 D8 六、申請專利範圍 一偶合之密度檷雄物Μ及已檷記AAAC抗體之量至少為預 \ 期檷的分析物之量之兩倍。 _ 11 一種Μ離心分析生物性流«檢《中是否含有免疫球蛋白 亞群之裝置，該裝置包括： a) —個透明試管，其具接受流臞檢«之孔徑； b) —種在該試管孔徑中之嵌入物•其係固定在試管底 部，或可於試管孔徑中自由移動而其比重可使其於檢體 離心時沈降至試管底部； c) 位於該試管孔徑上部之密度標識物•該禰雄物為與 -免疫球蛋白-特異性抗體及/或抗原偁合之具不同比重 之微粒或微脂粒； d) 在試管孔徑中之可操作量已標記抗一抗原一抗體一 複合物（AAAC)抗《，該AAAC抗體對該密度檷雄物上形 成之免疫球蛋白抗«_抗原複合物有特異性•且可使該 偁合體被偵測出來；及 e) —種離心装置，可使密度檷識物在該試管孔徑中依 密度分成相間隔之帶或環狀。 12. 一種Μ離心分析生物性流II檢《中是否含有免疫球蛋白 亞群乏装置，該裝置包括： /a)—儸透明試管，其具複式漏斗狀孔徑•開孔蝙膨大 而末端狭窄； b)位於該孔徑膨大端之密度檷識物，該檷識物為與免 疫球蛋白-特異性抗«及/或抗原偁合之具不同比重之 微粒或微脂粒； -4- 本紙張尺度適用中國國家標準（CNS)A4规格（210 X 297公輦） -----.-------「裝---------.訂J-----線 (請先閱讀背面之注意事項再塡寫本頁) 297094 A8 B8 C8 D8 七、申請專利範圍 C)在試管孔徑中之可搮作量巳檷記抗一抗原一抗體一 複合物（AAAC)抗《，該AAAC抗髑對該密度欏識物上形 ··»- 成之免疫球蛋白抗體一抗原複合物有特異性，且可使該 偶合體被偵测出來；及 d)—種離心装置，可使密度檷識物在該試管孔徑中依 密度分成相間隔之帶或環狀。 -----：-------叫J裝---------.訂IH-----「—線 (請先閱讀背面之注意事項再塡寫本頁) 經濟部中央標準局员工消費合作社印製 本紙張尺度適用中國國家標準（CNS)A4规格（21〇 X297公箄）
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US5460979A (en) 1995-10-24
CN1088310A (zh) 1994-06-22
US5834217A (en) 1998-11-10
US5342790A (en) 1994-08-30
US5776710A (en) 1998-07-07
ATE197993T1 (de) 2000-12-15
AU4870993A (en) 1994-05-12
US5635362A (en) 1997-06-03
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DE69329726D1 (de) 2001-01-11
JPH06281651A (ja) 1994-10-07
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JP2679945B2 (ja) 1997-11-19
NO933919D0 (no) 1993-10-29
AU668212B2 (en) 1996-04-26
US5759794A (en) 1998-06-02
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EP0595641A3 (en) 1995-04-26
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