Multiple-site sample-handling apparatus and method

• US 20030017467A1
• Filed: 08/23/2001
• Published: 01/23/2003
• Est. Priority Date: 02/18/2000
• Status: Abandoned Application

• Current Assignee: Aclara Biosciences, Inc (Laboratory Corporation Of America Holdings)
• Original Assignee: Aclara Biosciences, Inc (Laboratory Corporation Of America Holdings)
• Inventors: Albagli, David, Boone, Travis D., Hooper, Herbert H., Singh, Sharat, Anderson, Rolfe, Ricco, Antonio J.
• Application Number:
  US09/938,439
• Publication Number:
  US 20030017467A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00418 using pressure
• CPC Class Codes: B01J 2219/00454 by chemical cleavage from the solid support
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• 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 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00833 Plastic
• CPC Class Codes: B01J 2219/0086 : Dimensions of the flow channels
• CPC Class Codes: B01J 2219/00873 : Heat exchange
• CPC Class Codes: B01L 2200/027 : for microfluidic devices
• CPC Class Codes: B01L 2200/0673 : Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/16 : Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/087 : Multiple sequential chambers
• CPC Class Codes: B01L 2300/0883 : Serpentine channels
• CPC Class Codes: B01L 2300/0887 : Laminated structure
• CPC Class Codes: B01L 2400/0409 : centrifugal forces
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 : electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• CPC Class Codes: B01L 3/5027 : by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: B01L 3/527 : for a plurality of reagents
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A microchannel apparatus and method for processing a sample are disclosed. The apparatus include a multisite reaction channel, one or more sample-preparation stations upstream of the reaction channel, for carrying out one or more selected sample-preparation steps effective to convert a sample to the bulk-phase medium, and one or more product-processing stations downstream of the reaction channel, for processing products generated in one or more of the reaction regions. Also included is structure for transferring solvent or solvent components between one of the sample-preparation stations and one or more selected reaction regions in the reaction channel, and between one or more selected reaction regions in the reaction channel and one of said product-processing stations, under the control of a control unit.

Claims

1. A microchannel sample-handling apparatus for processing a sample, comprising

(a) a microchannel device having

(i) a substrate,

(ii) an elongate or planar multisite reaction channel formed in said substrate for receiving a bulk-phase medium containing sample components, said reaction channel having a plurality of reaction regions and region-specific reagents associated with each region, for simultaneously conducted different reactions on sample components within the reaction channel,

(iii) one or more sample-preparation stations in said substrate, upstream of said reaction channel, for carrying out one or more selected sample-preparation steps effective to convert a sample to such bulk-phase medium, and

(iv) one or more product-processing stations downstream of said reaction channel, for processing products generated in one or more of said reaction regions,

means for transferring solvent or solvent components between one of said sample-preparation stations and one or more selected reaction regions in the reaction channel, and between one or more selected reaction regions in the reaction channel and one of said product-processing stations, and

a control unit for activating said transfer means, to effect transfer, in a selected reaction region, of solvent or solvent components from or to each hold or region-specific reservoir, to or from the associated reaction region.

2. The apparatus of claim 1, which further includes a second reaction chamber for receiving a second bulk-phase medium containing sample components, said second reaction channel having a plurality of reaction regions and region-specific reagents associated with each region, for simultaneously conducting different reactions on sample components within the reaction channel.

3. The apparatus of claim 2, wherein the reaction regions in the first-mentioned reaction channel are operatively connected to associated reaction regions in the second reaction channel via gated side channels, and said control means is operative to transfer reaction components directly between associated reaction regions in the two reaction channels.

4. The apparatus of claim 2, wherein reaction regions in the first-mentioned reaction channel are operatively connected to reaction regions in the second reaction channel via a common hold reservoir which receives sample components from reaction regions in one reaction channel, and supplies the combined components to reaction regions in the other reaction channel.

5. The apparatus of claim 2, wherein the two reaction chambers are formed in different layers of the device, and reaction regions in the two channels are interconnected by side channels extending between the two layers.

6. The apparatus of claim 5, wherein at least one of the two reaction channels include capillary-tube ports adapted to receive a capillary tube therein, for supplying or removing a selected reagent or component to or from that port.

7. The apparatus of claim 1, wherein at least some of said stations and the reaction channel include capillary-tube ports adapted to receive a capillary tube therein, for supplying or removing a selected reagent or component to or from that port.

8. The apparatus of claim 1, wherein said sample-preparation stations include at least one of a cell-culture station, a station at which cells grown in the cell-culture station are lysed, and a reservoir containing lysing medium.

9. The apparatus of claim 1, wherein said product-processing stations include a station selected from the group consisting of:

(a) a waste reservoir for receiving selected components from the reaction regions;

(b) a capture station at which selected components from the reaction channel are captured and concentrated;

(c) an assay-reagent reservoir from which assay components are added to sample components;

(d) an assay station from which assay components are added to sample components;

(e) a separation channel at which sample components can be separated; and

(e) a second multisite reaction channel.

10. The apparatus of claim 9, wherein which further includes a detector for detecting the presence of absence of selected components contained in selected reaction regions, and the control unit is operable to move selected reaction components to other stations in the device, based on the presence of absence of such detected components.

11. The apparatus of claim 5, wherein the two layers are detachable reaction modules, allowing one module to be replaced by another during a sample-processing operation, where the two modules include alignable fluid-transfer channels and alignment structure for placing the modules in an aligned condition, allowing fluid transfer across the aligned channels.

12. A method of analyzing components in a sample, comprising

applying the sample to the microchannel device in the apparatus of claim 1, operating the apparatus to process the sample, forming a bulk-phase medium containing sample components,

operating the apparatus to transfer the bulk phase medium into the multisite reaction channel in the apparatus, under conditions that promote simultaneous reactions with sample components and region-specific reagents in the channel,

operating the device to transfer one or more reacted components from the reaction channel into a processing station, to achieve at least one of the following results:

(a) removal of one or more reacted components produced in the reaction channel;

(b) assay of one or more reacted components produced in the reaction channel;

(c) further reaction of one or more reacted components produced in the reaction channel,

(d) mixing of two or more selected components contained or produced in the reaction channel;

(e) transfer of one or more selected components produced in the reaction channel to selected reaction region(s) in a second multisite reaction channel.in the device;

(f) separation of components contained in the reaction channel, or produced subsequently in the device, a separation medium; and

(g) detection of components contained in the reaction channel, or produced subsequently in the device, by a detector in the device.

13. The method of claim 12, wherein said operating includes assaying one or more components produced in selected regions of the reaction channel;

and based on the results of said assaying, transferring selected components to another station in the device.

14. The method of claim 12, which includes transferring reaction components from one or more regions in one reaction channel to one or more regions in a second reaction channel in the apparatus.