System and method for high throughput sample preparation and analysis using column chromatography

• US 20020160521A1
• Filed: 06/27/2001
• Published: 10/31/2002
• Est. Priority Date: 04/25/2001
• Status: Active Grant

• Current Assignee: BIOCIUS Life Sciences, Inc. (Agilent Technologies, Inc.)
• Original Assignee: BioTrove, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Linton, John, Hunter, Ian W., Ozbal, Can
• Granted Patent: US 6,812,030 B2
• Time in Patent Office: Days
• US Class Current: 436/161
• CPC Class Codes: B01F 25/14 Mixing drops, droplets or bodies of liquid which flow together or contact each other micromixers using where the materials to be mixed are in the form of droplets B01F33/302
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00414 using suction
• CPC Class Codes: B01J 2219/00418 using pressure
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00515 in the shape of strings
• CPC Class Codes: B01J 2219/00518 in the shape of tapes
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01L 2300/0812 : Bands; Tapes
• CPC Class Codes: B01L 2300/0845 : Filaments, strings, fibres, i.e. not hollow
• CPC Class Codes: B01L 3/0262 : using touch-off at substrate or container
• CPC Class Codes: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B01L 3/505 : flexible containers not provided for above
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2030/628 : Multiplexing, i.e. several columns sharing a single detector
• CPC Class Codes: G01N 2030/8417 : the store moving as a whole, e.g. moving wire
• CPC Class Codes: G01N 2035/1037 : Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 2035/1046 : Levitated, suspended drops
• CPC Class Codes: G01N 30/18 : using a septum or microsyringe
• CPC Class Codes: G01N 30/24 : Automatic injection systems
• CPC Class Codes: G01N 30/466 : with separation columns in parallel
• CPC Class Codes: G01N 30/7233 : interfaced to liquid or supercritical fluid chromatograph interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04
• CPC Class Codes: G01N 30/7266 : by electric field, e.g. electrospray
• CPC Class Codes: G01N 30/84 : Preparation of the fraction to be distributed
• CPC Class Codes: G01N 35/00009 : provided with a sample supporting tape, e.g. with absorbent zones
• CPC Class Codes: G01N 35/1095 : for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00
• CPC Class Codes: Y10T 436/115831 : Condition or time responsive

Abstract

A system and method high throughput sample preparation and analysis using column chromatography. Each port in a plurality of ports has a port input that interfaces with a first fluid source and a port output. A fluidic circuit is coupled to each port output and to a second fluid source, the fluidic circuit for controlling fluid flow from the plurality of ports and the second fluid source. The fluidic circuit is also coupled to a plurality of chromatography columns. An interface to an analyzer receives output from at least one of the plurality of chromatography columns. The plurality of chromatography columns is moved relative to the analyzer via a translation stage, such that sample output from one of the plurality of chromatography columns can be selectively presented to the analyzer.

Claims

1. A system for high throughput sample preparation and analysis using column chromatography, the system comprising:

a) a plurality of ports, each port having both a port input that interfaces with a first fluid source and a port output;

b) a fluidic circuit coupled to each port output and to a second fluid source, the fluidic circuit for controlling fluid flow from the plurality of ports and the second fluid source;

c) a plurality of chromatography columns, each chromatography column coupled to the fluidic circuit;

d) an interface to an analyzer that receives output from at least one of the plurality of chromatography columns; and

e) a translation stage that allows for movement of the plurality of chromatography columns relative to the analyzer, such that sample output from one of the plurality of chromatography columns can be selectively presented to the analyzer.

2. A system according to claim 1, further comprising a plurality of syringes, each syringe for aspirating a sample to be analyzed and for acting as the first fluid source for one of the plurality of ports.

3. A system according to claim 2, wherein the plurality of syringes are in fixed positions relative to each other.

4. A system according to claim 3, wherein the plurality of syringes are positioned in a linear array with 9 millimeter spacing between each of the syringes.

5. A system according to claim 3, wherein the plurality of syringes interface with the plurality of ports in a parallel manner.

6. A system according to claim 2, further comprising a controller for controlling the plurality of syringes, the controller comprising at least one device from the group of devices consisting of a robot, a translational stage, and a computer.

7. A system according to claim 2, wherein each port includes a compression fitting for interfacing with one of the plurality of syringes.

8. A system according to claim 2, further comprising a washing station for cleaning the array of syringes.

9. A system according to claim 2, wherein the sample to be analyzed is located on a movable surface.

10. A system according to claim 9, wherein the movable surface is a fiber.

11. A system according to claim 9, wherein the movable surface is a laminate.

12. A system according to claim 9, wherein the movable surface is a belt.

13. A system according to claim 1, wherein the first fluid source includes a plurality of tubes, each tube for interfacing with one of the plurality of ports.

14. A system according to claim 1, wherein the fluidic circuit includes:

a) a plurality of valves, each valve controlling fluid flow from the port output of one of the plurality of ports;

b) a plurality of tee unions, each tee union coupled to one of the plurality of valves and at least one chromatography column.;

c) a pump for pumping fluid from a second fluid source; and

d) at least one selection valve for selectively coupling an output from the pump to at least one of the plurality of tee unions.

15. A system according to claim 14, wherein at least one of the plurality of valves is an actively controlled shutoff valve.

16. A system according to claim 14, wherein at least one of the plurality of valves is a passive check valve.

17. A system according to claim 1, wherein the interface includes a plurality of electrospray ionization sprayer tubes for interfacing with a mass spectrometer, each electrospray ionization sprayer tube coupled to one of the chromatography columns.

18. A system according to claim 1, wherein the plurality of chromatography columns are in fixed positions relative to each other.

19. A system according to claim 1, wherein the plurality of chromatography columns are positioned in a fixed linear array.

20. A method for high throughput sample preparation and analysis using column chromatography, the method comprising:

a) interfacing a plurality of ports with a first fluid source, each port having both a port input coupled to the first fluid source and a port output;

b) controlling fluid flow from each port output and a second fluid source to a plurality of chromatography columns; and

c) moving the plurality of chromatography columns relative to the analyzer, such that sample output from one of the plurality of chromatography columns can be selectively presented to the analyzer.

21. The method according to claim 20, further comprising:

a) aspirating samples into a plurality of syringes, and

b) interfacing the plurality of syringes with the plurality of ports.

22. The method according to claim 21, further comprising controlling the syringes using at least one device from the group of devices consisting of a robot, a translational stage, and a computer.

23. The method according to claim 21, further comprising cleaning the syringes at a washing station prior to aspirating samples.

24. The method according to claim 20 wherein controlling fluid flow from each port output and a second fluid source to a plurality of chromatography columns includes:

a) controlling a plurality of valves so as to regulate fluid flow from the port output of each of the plurality of valves to a plurality of tee valves, each tee valve coupled to at least one of the plurality of chromatography columns; and

b) selectively pumping fluid from the second fluid source to at least one of the plurality of tee valves.

25. The method according to claim 20, further comprising presenting sample from one of the plurality of chromatography columns to a mass spectrometer using an electrospray ionization sprayer tube.

26. The method according to claim 25, further comprising blocking undesired components from entering the mass spectrometer by removing the voltage applied to the electrospray ionization sprayer tube.

27. The method according to claim 25, further comprising blocking undesired components from entering the mass spectrometer by moving the electrospray ionization sprayer tube to a position in which the spray is physically blocked from entering the mass spectrometer.

28. The method according to claim 20, further comprising performing at least one operation from the group of operations consisting of optical interrogation and mass spectrometry.

29. The method according to claim 27, wherein optical interrogation includes at least one of flouresence spectrometry, Raman spectrometry, and UV absorption.

30. The method of claim 20, wherein controlling fluid flow includes delivering samples and wash from one of the plurality of ports to one of the plurality of chromatography columns in one substantially continuous action.

31. The method according to claim 20, wherein sample output can be selectively presented to the analyzer once every specified time period.