CN1520330A - 使用柱色谱用于高通量样品制备和分析的***和方法 - Google Patents
使用柱色谱用于高通量样品制备和分析的***和方法 Download PDFInfo
- Publication number
- CN1520330A CN1520330A CNA028127870A CN02812787A CN1520330A CN 1520330 A CN1520330 A CN 1520330A CN A028127870 A CNA028127870 A CN A028127870A CN 02812787 A CN02812787 A CN 02812787A CN 1520330 A CN1520330 A CN 1520330A
- Authority
- CN
- China
- Prior art keywords
- sample
- fluid
- port
- chromatographic columns
- perfusor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/14—Mixing drops, droplets or bodies of liquid which flow together or contact each other
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
-
- 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
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
-
- 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
- B01L3/02—Burettes; Pipettes
- B01L3/0241—Drop counters; Drop formers
- B01L3/0262—Drop counters; Drop formers using touch-off at substrate or container
-
- 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
- B01L3/02—Burettes; Pipettes
- B01L3/0241—Drop counters; Drop formers
- B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
-
- 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
- B01L3/505—Containers for the purpose of retaining a material to be analysed, e.g. test tubes flexible containers not provided for above
-
- 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
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00009—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with a sample supporting tape, e.g. with absorbent zones
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
-
- 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
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/0036—Nozzles
-
- 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
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00387—Applications using probes
-
- 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
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00414—Means for dispensing and evacuation of reagents using suction
-
- 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
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00418—Means for dispensing and evacuation of reagents using pressure
-
- 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
- B01J2219/00277—Apparatus
- B01J2219/00479—Means for mixing reactants or products in the reaction vessels
-
- 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
- B01J2219/00277—Apparatus
- B01J2219/00495—Means for heating or cooling the reaction vessels
-
- 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
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00513—Essentially linear supports
- B01J2219/00515—Essentially linear supports in the shape of strings
-
- 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
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00513—Essentially linear supports
- B01J2219/00518—Essentially linear supports in the shape of tapes
-
- 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
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00585—Parallel processes
-
- 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
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/0059—Sequential processes
-
- 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
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00596—Solid-phase processes
-
- 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
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
-
- 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
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00657—One-dimensional arrays
-
- 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
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00659—Two-dimensional arrays
-
- 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
- B01J2219/0068—Means for controlling the apparatus of the process
- B01J2219/00686—Automatic
- B01J2219/00689—Automatic using computers
-
- 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
- B01J2219/0068—Means for controlling the apparatus of the process
- B01J2219/00702—Processes involving means for analysing and characterising the products
-
- 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
- B01J2219/0072—Organic compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0812—Bands; Tapes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
- B01L2300/0845—Filaments, strings, fibres, i.e. not hollow
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
-
- 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
- G01N2030/8411—Intermediate storage of effluent, including condensation on surface
- G01N2030/8417—Intermediate storage of effluent, including condensation on surface the store moving as a whole, e.g. moving wire
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
- G01N2035/1037—Using surface tension, e.g. pins or wires
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
- G01N2035/1046—Levitated, suspended drops
-
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/24—Automatic injection systems
-
- 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
-
- 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
-
- 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
- Y10T436/115831—Condition or time responsive
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Clinical Laboratory Science (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
一种使用柱色谱的高通量样品制备和分析的***和方法。多个端口的每一个端口具有与第一流体源面接的进样端口,和出口端口。流体环路与每一个出口端口面接,并连接到第二流体源,该流体环路用于控制来自多个端口和第二流体源的流体流动。流体环路也连接到多个色谱柱上。面接到分析仪上的连接装置接收来自多个色谱柱至少之一的输出。通过位移台使多个色谱柱相对分析仪移动,这样来自多个色谱柱其中之一的样品输出可被选择性地送到分析仪。
Description
技术背景
本发明涉及使用柱色谱用于高生产量样品制备和分析的***和方法,及样品分析,其中分析可包括质谱和光学访问,例如荧光光谱、拉曼光谱和紫外吸收。
背景技术
高通量筛选(HTS)是快速准确分析大量的相对选定目标物具有活性的化学化合物的方法。典型的化学库包括几十万到百万不同的化合物,所述的化合物相对各种各样的目标物进行筛选。大量的化合物必须进行常规筛选,导致需要能够快速而且定量分析的新技术。
通过起初的样品制备可增强对样品进行的各种分析。特别是,质谱是合适于许多HTS应用的独特的强大的技术手段。质谱仅基于其质量可准确地定量化合物,排除了开发特定光谱分析的需要。使用大气压离子化(API)连接装置的现有技术中的质谱仪不适合于含有高含量非挥发性盐或污染物溶液中样品的分析。样品中的非挥发性物质不仅可抑制所希望样品的信号,而且可使质谱仪不能工作,这是由于在离子导板和入口内沉淀物累积的结果。因此,在分析前样品必须净化以除去非挥发性污染物并除去盐。另外,如上所述,这必须以有利于高通量筛选的方式进行。
发明内容
本发明提出了使用柱色谱用于高通量样品制备和分析的***。该***包括多个端口,每一个端口不仅具有与第一流体源面接的进样端口,而且具有出口端口。流体环路与每一个端口连接,并连接到第二流体源,该流体环路用于控制来自多个端口和第二流体源的流体流动。流体环路也连接到多个色谱柱上。提供面接到分析仪上的连接装置,用于接收来自多个色谱柱至少之一的输出。位移台可使多个色谱柱相对分析仪移动,这样来自多个色谱柱其中之一的样品输出可被选择性地送到分析仪。
在本发明的一个实施方式中,该***包括多个注样器,每一个注样器用于吸入要分析的样品,并作为多个端口其中之一的第一流体源。多个注样器彼此相对处于固定的位置。例如,多个注样器可以每一个注样器之间9mm的间隔成直线排列而固定。多个注样器可以平行的方式与多个端口面接。多个注样器可由控制装置进行控制,所述的控制装置包括至少一种选自自控装置、位移台和计算机的设备。每一个端口可包括压紧装置用于面接多个注样器的其中之一。该***可包括洗涤台用于清洗注样器列。
在另一个相关的实施方式中,要分析的样品固定于可移动的表面。可移动的表面可以是纤维、层压材料、网或带。第一流体源可包括多个管,每一个管用于与多个端口的其中之一面接。
在本发明的另外相关的实施方式中,流体环路包括多个阀。每一个阀控制来自多个端口其中之一的出口端口的流体流动。提供多个T形连接器,每一个T形连接器与多个阀的其中之一及至少一个色谱柱连接。泵将流体从第二流体源泵出,至少一个选择阀选择性地将来自泵的输出连接到多个T形连接器的至少一个上。至少多个阀的其中之一是主动控制的关闭阀或被动的单向阀。
在本发明的另外相关的实施方式中,连接装置可包括用于和质谱仪面接的多个电子喷射离子化喷射器管;每一个电子喷射离子化喷射器管与色谱柱的其中之一连接。多个色谱柱彼此相对处于固定的位置,可以固定直线排列方式固定。
在本发明的又一个实施方式中,提供使用色谱柱的高通量样品制备和分析方法。多个端口与第一流体源面接,每一个端口不仅具有与第一流体源面接的进样端口,而且具有出口端口。流体流从每一个出口端口和第二流体源被控制地送入多个色谱柱。多个色谱柱相对分析仪可移动,这样来自多个色谱柱的其中之一的样品输出可被选择性地送到分析仪。
在本发明的相关的实施方式中,该方法进一步包括将样品吸入多个注样器,并将多个注样器与多个端口面接。注样器可使用选自自控装置、位移台和计算机的至少一种设备进行控制。在吸入样品前在洗涤台清洗注样器。
在本发明相关的实施方式中,控制从每一个出口端口和第二流体源到多个色谱柱的流体流动,包括多个可调节从多个阀每一个的出口端口到多个T形阀流体流动的阀,每一个T形阀与至少多个色谱柱的其中之一连接。流体选择性地从第二流体源被泵入多个T形阀的至少之一。
在本发明的另一个相关的实施方式中,所述的方法进一步包括将来自多个色谱柱其中之一的样品提供到使用电子喷射离子化的喷射器管的质谱仪中。通过移去施加到电子喷射离子化喷射器管的电压,或通过将电子喷射离子化喷射器管移动到喷射可被物理阻止进入质谱仪的位置,从而可阻止不希望的组分进入质谱仪。
在本发明的又一个相关的实施方式中,所述的方法进一步包括进行选自光学访问和质谱的至少一种操作。光学访问包括至少荧光光谱、拉曼光谱和紫外吸收的至少一种。控制流体流动包括在一个基本上连续的操作中,从多个端口其中之一到多个色谱柱其中之一输送样品并洗涤。每隔一定时间样品输出可选择性提供到分析仪上。
附图简述
本发明上述的特征通过参考以下详细的描述及结合参考附图更加容易理解,其中:
图1是描述本发明一个实施方式的用于高通量样品制备和分析方法的流程图;
图2是描述本发明一个实施方式的用于高通量样品制备和分析方法的示意图;
图3是描述本发明一个实施方式的用于高通量样品制备和分析方法的示意图;
图4是根据本发明一个实施方式的用于注样器列的位移台的示意图。
具体实施方式的详细描述
提出使用柱色谱的用于高通量样品制备和分析的***和方法。参考图1的流程图,其描述了本发明一个实施方式的高通量样品制备和分析的方法,大量的样品被吸入一个,或优选的实施方式中,多个注样器或管中,步骤41。注样器或管然后与多个端口面接,步骤42。流体环路控制流体从端口和第二流体源到多个色谱柱的流动,步骤43,所述的第二流体源在优选的实施方式中为洗涤缓冲液或溶剂。通过控制样品和/或洗涤缓冲液流体流动进入色谱柱,制备样品进行分析。通过位移台可控制色谱柱的位置,步骤44。这可使样品通过连接装置选择性地提供到分析仪,例如所述的分析仪可以是质谱仪,步骤45。该***能够以适合于高通量筛选的速度制备大量的样品进行分析。
使用柱色谱的样品制备包括但不限制于,精制和脱盐,可以使用本领域的普通技术人员熟悉的公认的技术实现。在列中的柱装填有具有理想表面化学的不溶凝胶、基质、聚合物或颗粒物(柱填充物)。大量的填充化学物可以得到,而且对于本领域的普通技术人员而言是熟知的。柱列可以均一地负载有给定的柱填充物,或不同的柱填充物可装填于柱列的每一个中。色谱的原理在于复杂混合物中单个组分与填充材料不同的亲核性。通常,对柱有亲核性的样品被负载于柱上。柱用缓冲液或溶剂洗涤,使不希望的污染物/盐流出离开柱,而保留感兴趣的样品。精制的样品然后用第二缓冲液或溶剂洗脱离开柱,所述的样品与所述的缓冲液或溶剂的亲核性比其与柱填充材料的亲核性高。另一类型的色谱在于根据组分的相对尺寸大小分离或精制复杂混合物中的组分。用该设备可进行的色谱通常的形式包括但不限制于,反相、离子交换、免疫亲核性、尺寸排斥及凝胶过滤。
根据本发明的一个实施方式,图2是本发明一个实施方式的用于高通量样品制备和和分析***的示意图。多个端口1与第一流体源面接。第一流体源可包括多个注样器或管(以下称为注样器)。在本发明不同的实施方式中,注样器列的针与色谱柱3的列通过端口1中的压紧装置连接。压紧装置形成围绕注样器针的流体紧密封。
多个端口1与控制流体到色谱柱流动的流体环路连接。在本发明的不同实施方式中,流体环路可包括置于列中每一个端口1和色谱柱3之间的阀2。阀2可以是主动控制关闭阀,或是被动单向阀,用于限制仅从端口1到色谱柱3的流动。流体环路也可包括列中的阀1和色谱柱3之间的T形连接器4,从其中将流出和洗涤缓冲液从泵***8加入到列中柱色谱3的每一个中。第二阀7控制泵***到特定的色谱柱的流动。阀7例如为单一的选择阀,或另外可由多个阀组成,每一个阀7可控制到多个色谱柱3其中之一的流动。
在列中柱3的每一个的洗出液被导入分析仪的连接装置4。分析仪可包括但不限制于,光学访问和质谱。可以进行的光学访问的类型包括荧光光谱、拉曼光谱和紫外吸收。连接装置4可包括连接到每一个柱3上的样品管,这样可将流体导入分析仪,或连接装置可更加复杂。例如,洗出液可被导入薄的金属管9中,在其上施加电压以进行直接的大气压电子喷射离子化从而用于质谱仪分析。
在连接装置与分析仪之间的相对取向,例如电子喷射离子化喷射器4与质谱仪的入口孔6之间的相对取向,可影响分析仪的运行性能。为使由此效应产生的内部样品偏差减少到最小,列中的每一个柱3和连接装置4可以直线布置方式排列并固定到适当的位置,整个列置于位移台上。整个排列然后相对于分析仪的入口孔6移动。在优选的实施方式中,对每一个样品而言,保持连接装置4与分析仪入口孔6之间的距离和相对取向。另外,来自列中每一个柱3的洗出液通过使用多歧管可被转换为单一的连接装置。如果在每一个独立的分析中清洗不适当,多歧管可能成为污染源。尽管可以用溶剂和/或缓冲液在每一次独立分析之间冲洗多歧管以进行适当的清洗,但该过程通常费时,而且限制了样品的分析速度。
在本发明的一个具体实施方式中,大量的样品被吸入一个,在优选的实施方式中,多个注样器中。在优选的实施方式中,注样器彼此相对位于固定的位置。注样器可以固定的直线排列方式进行固定,这样它们可以平行的方式与端口面接。另外,注样器可以9mm的间隔布置,这样有利于从标准96或384池的微量滴定板的转移。
要吸入的样品可被负载到可移动的表面。在不同的实施方式中,可移动的表面可为带,例如计时带、或纤维,如描述于US专利申请,序列号为09/081,700中,题目为“用于小滴微量化学的设备和方法”,其在此引入作为参考。可移动的表面可以是高通量处理小滴/样品***的一部分,如图3示意。***28可包括但不限制于,可移动的表面积21、施加到可移动表面26上的层压材料26、也可包括一列注样器的化合物再格式化器(reformatter)22、试剂加入台23、环境延迟室24、计算机控制29和至少一种分析仪25,例如质谱仪。通过多个注样器203将样品吸入离开层压材料26。如图2显示,注样器203然后通过端口1与色谱柱3面接。
在本发明的一个优选实施方式中,注样器被控制并准确地定位于三微空间中,注样器的活塞随所使用的位移台、自控装置和/或计算机控制而移动。图4是本发明一个实施方式的包括一列注样器31的位移台39的示意图。通过位移台39,注样器列在不同的平台之间移动,所述的平台包括但不限制于,由此样品3003可被吸入的可移动表面3001、一列色谱柱3002、洗涤台或洗涤缓冲液台。位移台39可包括挠性接头32或连接器,其可使扭矩传输到活塞驱动齿轮33上,从而使可能是分挡器或伺服马达的扭矩源远距离地安装。与包含有机载马达的装置相比,这极大地减少了注样器列组件34的质量。因此,相对目前的装置而言,当面接到固定的***时,整个组件几乎没有惯性,因此需要更少的加速动力。对于给定的施加力,也可以得到更大的加速。
在本发明的不同的具体实施方式中,使用齿条和小齿轮传动装置33***以使由马达施加到注样器列34上的转动转变为平动,其然后驱动注样器的活塞进出。注样器的活塞可与其他的活塞一起被驱动或被单独驱动。为防止反洗误差,可使用与活塞组件连接35的一对齿条。通过安装齿条传动件36,彼此在其长度方向略有位移,在驱动小齿轮33和活塞齿条36之间的反洗可在装配时间内被“消除”。
也可引入另外的传动装置,例如蜗轮驱动螺杆。活塞杆35可这样被驱动,包括将螺杆穿过活塞组件的一部分,或将螺杆牢固地连接到活塞组件65上并将螺杆穿过蜗轮的中心。每一种构造都需要将活塞组件机械固定到垂直的位移装置上。涡轮构造可在驱动***33与活塞组件34之间实现更高的从一端到另一端的齿轮齿数比。其也具有无支持驱动的优点,即活塞组件34可自锁,不需要扭矩使活塞组件保持在适当的位置。
在本发明的其他实施方式中,转动的由外部控制37的编码器38连接到驱动活塞组件34的驱动齿轮轴33上。通过使用转动的编码器38,当其从注样器中分配时可实现流体的精确计量。
位移台32这样连接到定位***中从而固定注样器列31以从移动表面或层压材料32中吸入样品34。在吸入样品后,例如可移动注样器列,因此它们与多个端口36面接,所述的端口通过流体环路38连接到色谱柱37上。样品34然后被处理和分析。
根据本发明的一个实施方式,在吸入样品前,大体积的洗涤缓冲液或溶剂被吸入注样器列的筒中。要分析的样品与含有一小塞空气的该体积分离。样品体积被吸入注样器列中,这样样品被限制在注样器列的针中。注样器然后被移动并送入柱3列中的端口1(参考图2)的压紧装置中。每一个阀2开启,柱3列的阀7关闭。通过同时压下注样器列的活塞,整个注样器列然后被置于柱3列上。位于注样器针中的样品被置于色谱柱3上,及杂质/盐用注样器筒中的洗涤缓冲液从柱中洗去。此时柱列3位于这样的位置,要使来自柱3任一个的洗涤缓冲液不能进入质谱仪的入口6。在注样器中的内容物被排出后,关闭阀2。注样器列然后与注样器端口1的压紧装置分离,随后在清洗台上进行洗涤,筒中装满洗涤缓冲液或溶剂,一塞量空气及下一批样品被吸入。
为使样品流出离开色谱柱列,关闭每一个阀2。此刻,将适当的电压施加到金属定位的夹具中,使构成API质谱连接装置的每一个电子喷射针4带电。也可以应用质谱仪连接装置中使用的屏蔽和/或保护气体。柱列3通过位移台移动,这样在列中的第一柱可向质谱仪入口的孔喷射。在列中的单个色谱柱的阀7选择性地开启,洗出液缓冲液被选择性地输送到列3中单个柱中。洗出液缓冲液使脱盐和精制的样品从选择的柱中流出通过上述的API连接装置进入质谱仪。列3中的每一个色谱柱中的样品独立地这样分析,即通过仅开启选择柱的阀7,而同时使其他柱的阀关闭,选择性地将来自泵送***8的洗出液缓冲液或溶剂输送到那个柱中。下一个样品是这样分析的,即使用位移台移动柱列3,这样下一个柱可喷射进入质谱仪的进入孔6中,开启阀7将洗出液缓冲液或溶剂选择性地输送到那个柱。刮板9永久性地固定在质谱仪入口孔6的前面,以保证来自已经被分析的柱的残余喷射不进入质谱仪。一旦每一个柱中的样品被分析,施加到金属管的电压,如果施加,则关闭质谱仪API连接装置的屏蔽和/或保护气体,柱列3移动到初始的位置,其中没有任何的柱喷射进入质谱仪。这样停止了样品进入质谱仪的喷射,保护设备不受任何不希望的污染物和/或盐的影响。
在列中的色谱柱然后这样被清洗,即开启阀7,用过量的洗出液缓冲液冲洗每一个柱。柱3可以单独地以并联或串联的方式进行清洗。清洗的柱用同样由泵送***8输送的洗涤缓冲液或溶剂进行类似的再平衡。在这一点再开始循环,下一批样品从注样器的列中被输送到色谱柱列3中。
以下提供本发明一个具体实施方式的例子。该例子并非意欲限制本发明的范围。在96池的微量滴定板上进行酶的抑制分析。96池的每一个池包括100μl磷酸盐缓冲盐水中10μg的胰岛素及用于所述酶的10μmol缩氨酸底物。在这样的条件下,胰岛素使缩氨酸底物断裂为两种较小的缩氨酸。在加入底物之前,来自上述选择的化学品库中的不同的化学品以不同的浓度加入到96池中以确定,那个化合物,如果有,抑制底物向产物的转化。酶-底物-抑制剂混合物在96池的微量滴定板上37℃下培养1小时,加入10μl的甲醇以使酶改变本性进而停止反应。在每一个池中的相对抑制这样被定量,即摄取反应混合物的质谱,并比较产物和底物的量。在来自化学品库的化合物导致高度抑制的反应中,相对产物有大量的底物,而如果几乎没有或没有发生抑制的情况,相对底物有更大量的产物。
具有9mm间隔排列的钝尾22计量针的直线排列的12个气密25μl微量注样器作为注样器列。直线排列的0.7mm内径、4mm长的柱,同样具有9mm的间隔作为色谱柱列3(见图1)。装填有5μm氧化硅珠上有十八烷基表面化学品的反相柱填充材料作为色谱的介质。50μm内径、12cm长的金属管连接到列3中每一个色谱柱的出口端,作为色谱柱和质谱仪入口6之间的连接装置4。通过使金属定位夹具带电将3000V的电势施加到所有的12个管4上,从而使电子喷射离子化进入质谱仪的入口6。
通过反复将甲醇吸入注样器中在注样器清洗台中清洗注样器列。20μl的10%甲醇和0.5μl的气塞在下一个台中吸入到注样器中。注样器组然后移过微量滴定板,将1μl反应混合物吸入注样器针中。1μl样品位于注样器的针中,通过气塞在注样器中与20μl的10%甲醇分离。注样器列通过注样器端口1的压紧装置被送入色谱柱列3中。在注样器端口1和列3中的柱之间的阀2是微量单向阀,可允许从注样器到柱3的单一方向的流动。微型隔膜阀7位于泵送***和列中每一个柱头部的T形连接器之间。这些阀7阻挡了流体流动,除非由通过它们的液流启动。注样器列的筒被压下,样品装填到柱3中。底物和反应产物吸附到柱填充材料上,并被保留。注样器筒中的20μl 10%的甲醇洗涤盐(来自磷酸缓冲盐水),沉淀的酶通过柱,洗出液收集在位于质谱仪连接装置下面的废物容器中。保护质谱仪以免受盐和污染物的影响,因为电压没有施加到金属管4中,结果没有发生电子喷射离子化。注样器列从压紧装置中移开,开始进行清洗注样器列和吸入下一批样品的过程。
3000V的电压同时施加到构成质谱仪连接装置的色谱柱的出口端部的所有12个金属管4上。电压的施加形成非常少量的液体从每一个管4中喷射出进入质谱仪,甚至在没有正向液体流动压力的情况下。该流体仅由10%的甲醇洗涤溶剂组成,因为重要的样品仍结合在柱上。柱列3利用位移台移动,这样列中的第一柱可通过刮板9中的开孔喷射进入质谱仪的入口孔6。在列中第一柱的膜阀7利用施加电流选择性开启,80%的甲醇以5μl/s的速度从泵送***8中进入到柱中。在柱和注样器端口1之间的单向阀2阻止流体向上流离开注样器端口并迫使其移动通过色谱柱3。80%的甲醇迅速地从柱3中洗提出感兴趣的样品(即,底物和/或产物),通过电子喷射连接装置4将样品喷射入质谱仪的入口6。阀7保持开启0.5秒,其已足够长以获得可接受的质谱仪信号。0.5秒后关闭阀7,整个柱列3又一次利用位移台移动,这样列3中的第二柱被喷射进入质谱仪。列中的该第二柱的隔膜阀7被开启,选择性地将80%的甲醇洗提溶剂输送到柱中。以这样的方式,列3中12个柱的每一个中的样品用质谱仪分析,储存数据用于以后的分析。一旦最后的样品分析后,停止给金属管4施加电压,样品不再喷射进入质谱仪的入口6。利用位移台柱列3移动到起始的位置,这样所有的电子喷射针4被阻止喷射进入质谱仪。
为洗涤列3中的柱,所有的隔膜阀7被同时开启,80%的甲醇以20μl/s的速度3秒钟输送到整个色谱柱列3中。通过以20μl/s的速度输送10%的甲醇2秒然后使柱列3再次平衡。总的样品分析时间一共持续6秒,12个样品的每一个用0.5秒,而洗涤和柱再生需要5秒,这样平均的样品分析时间为每秒1个样品。
使用的质谱仪是三个四极质谱仪,程序化操作选择离子监视(SIM)模式,这样仅底物和两种产物的质量被连续监视。以仪器性能最大的每次扫描约20毫秒的速度得到质谱仪扫描。每个样品一共20次扫描进行平均以得到最后的定量结果。在阀启动样品切换期间得到低的总信号用作引发物以开始下一样品的质谱分析。通过获得每一个样品的产物与底物比,可以确定在微量滴定板的每一个池中发生的相对抑制量。
尽管已经公开了本发明的各种实例性实施方式,但在不背离真实范围的前提下,对于本领域的普通技术人员而言,对本发明可进行各种改变和变化,实现本发明的一些优点,这是显而易见的。这些和明显的变化意欲被所附的权利要求所覆盖。
Claims (31)
1.一种使用柱色谱的高通量样品制备和分析的***,该***包括:
a)多个端口,每一个端口不仅具有与第一流体源面接的进样端口,而且具有出口端口;
b)流体环路与每一个出口端口连接,并连接到第二流体源,该流体环路用于控制来自多个端口和第二流体源的流体流动;
c)多个色谱柱,每一个色谱柱连接到流体环路上;
d)面接到分析仪上的连接装置,用于接收来自多个色谱柱的至少之一的输出;及
e)位移台,其可使多个色谱柱相对分析仪移动,这样来自多个色谱柱其中之一的样品输出可被选择性地送到分析仪。
2.如权利要求1的***,进一步包括多个注样器,每一个注样器用于吸入要分析的样品,并作为多个端口之一的第一流体源。
3.如权利要求2的***,其中多个注样器彼此位于固定的位置。
4.如权利要求3的***,其中多个注样器以直线排列方式固定,每一个注样器之间具有9mm的间隔。
5.如权利要求3的***,其中多个注样器与多个端口以平行的方式面接。
6.如权利要求2的***,进一步包括控制多个注样器的控制装置,所述的控制装置包括至少选自自控装置、位移台和计算机中的一种设备。
7.如权利要求2的***,其中每一个端口包括用于与多个注样器之一面接的压紧装置。
8.如权利要求2的***,进一步包括用于清洗注样器列的洗涤台。
9.如权利要求2的***,其中要分析的样品被固定在可移动的表面上。
10.如权利要求9的***,其中可移动的表面为纤维。
11.如权利要求9的***,其中可移动的表面为层压材料。
12.如权利要求9的***,其中可移动的表面为带。
13.如权利要求1的***,其中第一流体源包括多个管,每一个管用于与多个端口之一面接。
14.如权利要求1的***,其中流体环路包括:
a)多个阀,每一个阀控制来自多个端口之一的出口端口的流体流动;
b)多个T形连接器,每一个T形连接器与多个阀之一及至少一个色谱柱连接;
c)泵,用于从第二流体源泵送流体;及
d)至少一个选择阀,用于选择性地将来自泵的输出连接到多个T形连接器的至少一个上。
15.如权利要求14的***,其中多个阀的至少一个是主动控制的关闭阀。
16.如权利要求14的***,其中多个阀的至少一个是被动的单向阀。
17.如权利要求1的***,其中连接装置包括多个电子喷射离子化喷射器管,用于面接质谱仪,每一个电子喷射离子化喷射器管与色谱柱之一连接。
18.如权利要求1的***,其中多个色谱柱彼此位于固定的位置。
19.如权利要求1的***,其中多个色谱柱以固定的直线排列方式固定。
20.一种使用柱色谱的高通量样品制备和分析的方法,该方法包括:
a)使多个端口与第一流体源面接,每一个端口不仅具有与第一流体源连接的进样端口,而且具有出口端口;
b)控制从每一个出口端口和第二流体源到多个色谱柱的流体流动;
c)相对于分析仪移动多个色谱柱,这样来自多个色谱柱其中之一的样品输出可被选择性地送到分析仪。
21.如权利要求20的方法,进一步包括:
a)将样品吸入多个注样器;及
b)使多个注样器与多个端口面接。
22.如权利要求21的方法,进一步包括使用至少选自自控装置、位移台和计算机中的一种设备控制多个注样器。
23.如权利要求21的方法,进一步包括在吸入样品前在洗涤台清洗注样器。
24.如权利要求20的方法,其中控制从每一个出口端口和第二流体源到多个色谱柱的流体流动,包括:
a)控制多个阀,这样以调节从多个阀每一个的出口端口到多个T形阀的流体流动,每一个T形阀与多个色谱柱的至少一个连接;及
b)选择性地将流体从第二流体源泵送到多个T形阀的至少之一。
25.如权利要求20的方法,进一步包括使用电子喷射离子化喷射器管,将样品从多个色谱柱其中之一提供到质谱仪。
26.如权利要求25的方法,进一步包括通过移去施加到电子喷射离子化喷射器管的电压,阻止不希望的组分进入质谱仪。
27.如权利要求25的方法,进一步包括通过将电子喷射离子化喷射器管移动到其中喷射被物理阻止进入质谱仪的位置,阻止不希望的组分进入质谱仪。
28.如权利要求20的方法,进一步包括进行选自光学访问和质谱的至少一种操作。
29.如权利要求27的方法,其中所述的光学访问包括荧光光谱、拉曼光谱和紫外吸收的至少一种。
30.如权利要求20的方法,其中控制流体流动包括在一次基本上连续的操作中,从多个端口的其中之一到多个色谱柱的其中之一输送样品并洗涤。
31.如权利要求20的方法,其中所述的样品输出每隔一定时间被选择性地提供给分析仪。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/893,311 US6812030B2 (en) | 2001-04-25 | 2001-06-27 | System and method for high throughput sample preparation and analysis using column chromatography |
US09/893,311 | 2001-06-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1520330A true CN1520330A (zh) | 2004-08-11 |
Family
ID=25401365
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA028127870A Pending CN1520330A (zh) | 2001-06-27 | 2002-06-04 | 使用柱色谱用于高通量样品制备和分析的***和方法 |
Country Status (6)
Country | Link |
---|---|
US (2) | US6812030B2 (zh) |
EP (1) | EP1412046A1 (zh) |
JP (1) | JP2004531738A (zh) |
CN (1) | CN1520330A (zh) |
CA (1) | CA2450695A1 (zh) |
WO (1) | WO2003002226A1 (zh) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006119705A1 (fr) * | 2005-05-11 | 2006-11-16 | Accelergy Shanghai R & D Center Co., Ltd | Systeme de traitement de materiaux a haut debit |
CN100502995C (zh) * | 2004-09-10 | 2009-06-24 | 吉尔森公司 | 具有可调节盘的馏分收集器 |
CN103201003A (zh) * | 2010-09-20 | 2013-07-10 | Abbvie公司 | 采用模拟移动床色谱纯化抗体 |
CN101602019B (zh) * | 2008-05-14 | 2013-08-21 | 亚申科技研发中心(上海)有限公司 | 高通量催化剂处理方法及其*** |
CN108511315A (zh) * | 2011-12-28 | 2018-09-07 | 英国质谱有限公司 | 碰撞离子发生器和分离器 |
CN109331893A (zh) * | 2018-11-22 | 2019-02-15 | 复旦大学 | 微流控自由流纸色谱阵列喷雾质谱联用装置 |
CN109772208A (zh) * | 2019-01-29 | 2019-05-21 | 山西省农业科学院果树研究所 | 一种红枣内维生素含量测定装置及方法 |
CN109923413A (zh) * | 2016-11-15 | 2019-06-21 | 株式会社资生堂 | 多级色谱分析方法及分析*** |
CN111108379A (zh) * | 2017-09-14 | 2020-05-05 | 惠普发展公司,有限责任合伙企业 | 色谱表面增强发光(sel)感测 |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6893877B2 (en) | 1998-01-12 | 2005-05-17 | Massachusetts Institute Of Technology | Methods for screening substances in a microwell array |
US20040047765A1 (en) * | 1998-10-16 | 2004-03-11 | Gordon Steven J. | Automated robotic workstation and methods of operation thereof |
NZ513390A (en) | 1999-03-19 | 2003-01-31 | Genencor Int | Multi-through hole testing plate for high throughput screening |
US20020151040A1 (en) | 2000-02-18 | 2002-10-17 | Matthew O' Keefe | Apparatus and methods for parallel processing of microvolume liquid reactions |
US20010055765A1 (en) | 2000-02-18 | 2001-12-27 | O'keefe Matthew | Apparatus and methods for parallel processing of micro-volume liquid reactions |
US8414774B2 (en) * | 2001-04-25 | 2013-04-09 | Agilent Technologies, Inc. | Systems and methods for high-throughput screening of fluidic samples |
US7588725B2 (en) * | 2001-04-25 | 2009-09-15 | Biotrove, Inc. | High throughput autosampler |
US20050123970A1 (en) * | 2001-04-25 | 2005-06-09 | Can Ozbal | High throughput autosampler |
US6880576B2 (en) | 2001-06-07 | 2005-04-19 | Nanostream, Inc. | Microfluidic devices for methods development |
CN100528363C (zh) * | 2002-02-13 | 2009-08-19 | 安捷伦科技有限公司 | 微流体分离柱装置及其制备方法 |
US7261812B1 (en) | 2002-02-13 | 2007-08-28 | Nanostream, Inc. | Multi-column separation devices and methods |
US7132650B1 (en) | 2003-09-26 | 2006-11-07 | Nanostream, Inc. | High throughput multi-dimensional sample analysis |
US7214320B1 (en) | 2002-08-08 | 2007-05-08 | Nanostream, Inc. | Systems and methods for high throughput sample analysis |
US8277753B2 (en) | 2002-08-23 | 2012-10-02 | Life Technologies Corporation | Microfluidic transfer pin |
US20060094108A1 (en) * | 2002-12-20 | 2006-05-04 | Karl Yoder | Thermal cycler for microfluidic array assays |
US7682565B2 (en) | 2002-12-20 | 2010-03-23 | Biotrove, Inc. | Assay apparatus and method using microfluidic arrays |
US7074327B2 (en) * | 2003-05-08 | 2006-07-11 | Nanostream, Inc. | Sample preparation for parallel chromatography |
US20050032238A1 (en) * | 2003-08-07 | 2005-02-10 | Nanostream, Inc. | Vented microfluidic separation devices and methods |
US7028536B2 (en) * | 2004-06-29 | 2006-04-18 | Nanostream, Inc. | Sealing interface for microfluidic device |
US8277760B2 (en) | 2003-09-19 | 2012-10-02 | Applied Biosystems, Llc | High density plate filler |
US7998435B2 (en) | 2003-09-19 | 2011-08-16 | Life Technologies Corporation | High density plate filler |
JP4679368B2 (ja) | 2003-12-11 | 2011-04-27 | 一洋 今井 | 発現微量タンパク質/ペプチドの検出・分離・同定法 |
SE0303398L (sv) | 2003-12-12 | 2005-08-12 | Amersham Biosciences Ab | Reningssystem |
JP2007529015A (ja) | 2004-03-12 | 2007-10-18 | バイオトローブ, インコーポレイテッド | ナノリットルのアレイローディング |
US9086379B2 (en) * | 2004-05-24 | 2015-07-21 | OptoTrace (SuZhou) Technologies, Inc. | System for chemical separation and identification |
EP1766417B1 (en) * | 2004-06-14 | 2013-04-03 | Parker-Hannifin Corporation | Robotic handling system and method with independently operable detachable tools |
US20060105453A1 (en) | 2004-09-09 | 2006-05-18 | Brenan Colin J | Coating process for microfluidic sample arrays |
WO2006022822A1 (en) * | 2004-08-10 | 2006-03-02 | Prime Separations, Incorporated | Chromatographic separation member and method |
US7763848B2 (en) * | 2005-01-18 | 2010-07-27 | Phoenix S&T, Inc. | Apparatus and method for controlling an electrostatically induced liquid spray |
EP1849012A2 (en) * | 2005-01-28 | 2007-10-31 | Parker-Hannifin Corporation | Sampling probe, gripper and interface for laboratory sample management systems |
EP1963837A1 (en) * | 2005-12-05 | 2008-09-03 | Parker-Hannifin | Self-cleaning injection port for analytical applications |
JP2009518655A (ja) * | 2005-12-08 | 2009-05-07 | パーカー・ハニフィン・コーポレーション | 分析用アプリケーションのためのシリンジ洗浄ステーション |
US7807446B2 (en) * | 2006-02-13 | 2010-10-05 | Monsanto Technology Llc | High throughput system and methods for analyzing liquid formulations |
CA2703991A1 (en) * | 2007-11-02 | 2009-05-07 | Biotrove, Inc. | Devices and methods for coupling mass spectrometry devices with chromatography systems |
EP2637780B1 (en) | 2010-11-12 | 2022-02-09 | Gen9, Inc. | Protein arrays and methods of using and making the same |
US9551431B2 (en) | 2011-11-18 | 2017-01-24 | Korea Basic Science Institute | Gaseous sample injection valve and gaseous sample injection method using same |
EP2841929A4 (en) * | 2012-04-24 | 2016-03-23 | Hewlett Packard Development Co | DEVICE FOR CARRYING OUT A DETECTION APPLICATION |
WO2015106169A1 (en) * | 2014-01-10 | 2015-07-16 | PureHoney Technologies, Inc. | Mass-spectrometer systems and methods |
EP2944955A1 (en) * | 2014-05-13 | 2015-11-18 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Benchmark for LC-MS systems |
CN104407083B (zh) * | 2014-11-28 | 2016-08-31 | 天津博纳艾杰尔科技有限公司 | 全自动分离***及其在食用油极性组分分离中的应用 |
US10881985B1 (en) * | 2016-12-08 | 2021-01-05 | Elemental Scientific, Inc. | System with reusable column with resin packing and unpacking procedures and sample analysis |
IT201700024734A1 (it) * | 2017-03-06 | 2018-09-06 | Dani Instr Spa | Dispositivo campionatore perfezionato per gascromatografia |
EP3896443B1 (en) | 2020-04-15 | 2024-05-01 | F. Hoffmann-La Roche AG | Analytical system and method including switching between liquid chromatography fluidic streams |
Family Cites Families (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3566677A (en) | 1969-06-26 | 1971-03-02 | Atomic Energy Commission | Method and apparatus for monitoring content of flowing streams |
BE790280A (fr) | 1971-11-19 | 1973-04-19 | Technicon Instr | Analyse photometrique d'une goutellette d'un echantillon liquide |
US4111553A (en) | 1976-03-30 | 1978-09-05 | Unisearch Limited | Multi-sample transporting and heating apparatus for use in atomic absorption spectrometry |
FR2353856A1 (fr) | 1976-06-02 | 1977-12-30 | Chateau Guy | Ruban destine a servir de support a une reaction par exemple chimique ou biochimique, et procede d'analyse le mettant en oeuvre |
US4659677A (en) | 1983-05-26 | 1987-04-21 | Eastman Kodak Company | Method providing liquid mixing outside containers |
JPS6022478A (ja) | 1983-07-18 | 1985-02-04 | Shinsei Kogyo:Kk | 超音波リニアモータ |
US4837160A (en) | 1983-10-28 | 1989-06-06 | Gamma Biologicals, Inc. | Biological fluid assay system and method |
FR2565350B1 (fr) | 1984-06-05 | 1986-10-10 | Paris Nord Universite | Moyens propres a permettre le support, le traitement, le stockage et l'analyse automatiques en continu d'echantillons biologiques |
JPS633244A (ja) | 1986-06-24 | 1988-01-08 | Japan Spectroscopic Co | 赤外スペクトル測定のサンプリング法及び高速液クロと赤外分光光度計のインタ−フエイス並びに高速液クロ検出器用赤外分光光度計 |
US5006749A (en) | 1989-10-03 | 1991-04-09 | Regents Of The University Of California | Method and apparatus for using ultrasonic energy for moving microminiature elements |
DE4022061A1 (de) | 1990-07-11 | 1992-01-16 | Wollnik Hermann | Analysenvorrichtung mit elektrothermischem atomisator und massenspektrometer zur atom- und molekuelanalyse |
JPH0564718A (ja) | 1991-09-05 | 1993-03-19 | Daikin Ind Ltd | 濃縮方法および装置 |
WO1993007168A2 (en) * | 1991-09-30 | 1993-04-15 | Perseptive Biosystems, Inc. | Protein chromatography system |
US5334837A (en) | 1991-10-05 | 1994-08-02 | Horiba, Ltd. | Micro analytical method, sampling plate used in same, method of detecting organic compound by use of said micro analytical method, apparatus for same and method of dividing for micro-liquid flow |
DE69321748T2 (de) | 1992-02-20 | 1999-06-17 | Canon K.K., Tokio/Tokyo | Verfahren und Messapparatur zur Handhabung von Teilchen |
US5508200A (en) | 1992-10-19 | 1996-04-16 | Tiffany; Thomas | Method and apparatus for conducting multiple chemical assays |
DE69422070T2 (de) | 1993-01-29 | 2000-07-06 | Becton Dickinson And Co., Franklin Lakes | Kompakter Blut-Kultur-Apparat |
US5486337A (en) | 1994-02-18 | 1996-01-23 | General Atomics | Device for electrostatic manipulation of droplets |
DK0764046T3 (da) | 1994-06-16 | 2000-12-18 | Dade Behring Marburg Gmbh | Fremgangsmåde og apparat til blanding af væsker |
IT1281156B1 (it) | 1995-07-03 | 1998-02-13 | Protec Srl | Selezionatrici per polveri e materiale particolato fine. |
US5630943A (en) * | 1995-11-30 | 1997-05-20 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Discontinuous countercurrent chromatographic process and apparatus |
WO1998008093A1 (en) | 1996-08-16 | 1998-02-26 | Oy Medix Biochemica Ab | Coated flexible thread-like solid carrier for immunoassays |
US5906223A (en) | 1996-09-16 | 1999-05-25 | Itt Industries, Inc. | Chromatography valve assembly |
WO1998015355A2 (en) | 1996-10-10 | 1998-04-16 | Corning Incorporated | Tool and method for transfer of drops |
US6309600B1 (en) | 1997-08-28 | 2001-10-30 | Biotrove, Inc. | Apparatus for droplet microchemistry |
US6123849A (en) | 1997-10-27 | 2000-09-26 | Millipore Corporation | Chromatographic column and valve |
US6066848A (en) | 1998-06-09 | 2000-05-23 | Combichem, Inc. | Parallel fluid electrospray mass spectrometer |
US6019897A (en) | 1998-08-20 | 2000-02-01 | Dyax Corporation | System for simultaneously pumping solvent for a plurality of chromatography columns |
AU2986400A (en) | 1999-02-08 | 2000-08-25 | Admetric Biochem Inc. | Chromatographic system with pre-detector eluent switching |
US6296771B1 (en) * | 1999-04-02 | 2001-10-02 | Symyx Technologies, Inc. | Parallel high-performance liquid chromatography with serial injection |
US6245297B1 (en) | 1999-04-16 | 2001-06-12 | Pe Corporation (Ny) | Apparatus and method for transferring small volumes of substances |
WO2000064557A1 (en) * | 1999-04-23 | 2000-11-02 | Advanced Bioanalytical Services, Inc. | High-throughput parallel liquid chromatography system |
FR2820058B1 (fr) | 2001-01-29 | 2004-01-30 | Commissariat Energie Atomique | Procede et systeme permettant de realiser en flux continu un protocole biologique, chimique ou biochimique |
-
2001
- 2001-06-27 US US09/893,311 patent/US6812030B2/en not_active Expired - Lifetime
-
2002
- 2002-06-04 WO PCT/US2002/017438 patent/WO2003002226A1/en not_active Application Discontinuation
- 2002-06-04 JP JP2003508456A patent/JP2004531738A/ja active Pending
- 2002-06-04 CN CNA028127870A patent/CN1520330A/zh active Pending
- 2002-06-04 EP EP02732017A patent/EP1412046A1/en not_active Withdrawn
- 2002-06-04 CA CA002450695A patent/CA2450695A1/en not_active Abandoned
-
2004
- 2004-05-27 US US10/855,198 patent/US6932939B2/en not_active Expired - Lifetime
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100502995C (zh) * | 2004-09-10 | 2009-06-24 | 吉尔森公司 | 具有可调节盘的馏分收集器 |
WO2006119705A1 (fr) * | 2005-05-11 | 2006-11-16 | Accelergy Shanghai R & D Center Co., Ltd | Systeme de traitement de materiaux a haut debit |
CN101602019B (zh) * | 2008-05-14 | 2013-08-21 | 亚申科技研发中心(上海)有限公司 | 高通量催化剂处理方法及其*** |
CN103201003A (zh) * | 2010-09-20 | 2013-07-10 | Abbvie公司 | 采用模拟移动床色谱纯化抗体 |
CN103201003B (zh) * | 2010-09-20 | 2016-04-13 | Abbvie公司 | 采用模拟移动床色谱纯化抗体 |
CN108511315A (zh) * | 2011-12-28 | 2018-09-07 | 英国质谱有限公司 | 碰撞离子发生器和分离器 |
CN108511315B (zh) * | 2011-12-28 | 2021-01-08 | 英国质谱有限公司 | 碰撞离子发生器和分离器 |
CN109923413A (zh) * | 2016-11-15 | 2019-06-21 | 株式会社资生堂 | 多级色谱分析方法及分析*** |
CN111108379A (zh) * | 2017-09-14 | 2020-05-05 | 惠普发展公司,有限责任合伙企业 | 色谱表面增强发光(sel)感测 |
CN109331893A (zh) * | 2018-11-22 | 2019-02-15 | 复旦大学 | 微流控自由流纸色谱阵列喷雾质谱联用装置 |
CN109772208A (zh) * | 2019-01-29 | 2019-05-21 | 山西省农业科学院果树研究所 | 一种红枣内维生素含量测定装置及方法 |
Also Published As
Publication number | Publication date |
---|---|
US6812030B2 (en) | 2004-11-02 |
JP2004531738A (ja) | 2004-10-14 |
CA2450695A1 (en) | 2003-01-09 |
US6932939B2 (en) | 2005-08-23 |
WO2003002226A1 (en) | 2003-01-09 |
EP1412046A1 (en) | 2004-04-28 |
US20040219071A1 (en) | 2004-11-04 |
US20020160521A1 (en) | 2002-10-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1520330A (zh) | 使用柱色谱用于高通量样品制备和分析的***和方法 | |
US7588725B2 (en) | High throughput autosampler | |
US8414774B2 (en) | Systems and methods for high-throughput screening of fluidic samples | |
US10317377B2 (en) | Monolithic column chromatography | |
AU766030B2 (en) | Parallel fluid electrospray mass spectrometer | |
EP2823280B1 (en) | Introducing samples into supercritical fluid chromatography systems | |
US20050123970A1 (en) | High throughput autosampler | |
JP4093201B2 (ja) | 液体クロマトグラフ | |
JP2007205954A (ja) | 3次元液体クロマトグラフィ | |
CN1955522A (zh) | 流路切换阀及使用该流路切换阀的高速液相色谱仪 | |
WO2005011832A2 (en) | A simultaneous multi-colum liquid chromatograph for direct sampling of an array of liquid samples | |
US20050214130A1 (en) | Multidimensional pump apparatus and method for fully automated complex mixtures separation, identification, and quantification | |
US20070023639A1 (en) | Liquid chromatographic apparatus | |
US7095017B2 (en) | Systems and method of a gated electrospray interface with variable flow rate for high throughput mass spectrometric analysis | |
CN1785476A (zh) | 一种全二维毛细管液相色谱分离*** | |
JPS6197567A (ja) | 試料の前処理方法 | |
GB2588635A (en) | Sample injector with fluidic sample mixing | |
JP4142587B2 (ja) | 溶液から分子を抽出するための合体可能なプロセシングモジュール | |
CN111610264A (zh) | 亲水作用色谱-反相色谱组合二维液相***及其分析方法 | |
AU2002303950A1 (en) | A system and method for high throughput sample preparation and analysis using column chromatography | |
CN209961743U (zh) | 纳流分馏器装置 | |
US20240136168A1 (en) | Methods and Apparatus for Washing Sampling Probe for Use in Mass Spectrometry Systems | |
CN117795333A (zh) | 使用样本微滴喷射进行类色谱分离 | |
CN117981050A (zh) | 分析***和方法 | |
WO2005036122A2 (ja) | 相互作用分析方法及び相互作用分析装置 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |