High throughput microfluidic systems and methods

• US 7,316,801 B2
• Filed: 09/16/2002
• Issued: 01/08/2008
• Est. Priority Date: 08/10/1998
• Status: Expired due to Fees

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Inventors: Toth, Andrew W., Kercso, Joseph E., Parce, J. Wallace, Chow, Calvin Y. H., Wolk, Jeffrey A., Sundberg, Steven A.
• Primary Examiner(s): Gordon; Brian R.
• Application Number:
  US10/244,227
• Publication Number:
  US 20030017085A1
• Time in Patent Office: 1,940 Days
• Field of Search: 422/63, 422/65, 422/66, 422/68.1, 422/100, 436/180, 436/43, 436/47
• US Class Current: 422/65
• CPC Class Codes: G01N 2035/00148 Test cards, e.g. Biomerieux or McDonnel multiwell test cards
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/113332 with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/119163 with aspirator of claimed structure
• CPC Class Codes: Y10T 436/25625 Dilution
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The invention provides improved systems, devices, and methods for analyzing a large number of sample compounds contained in standard multi-well microtiter plates or other array structures. The multi-well plates travel along a conveyor system to a test station having a microfluidic device. At the test station, each plate is removed from the conveyor and the wells of the multi-well plate are sequentially aligned with an input port of the microfluidic device. After at least a portion of each sample has been input into the microfluidic channel system, the plate is returned to the conveyor system. Pre and/or post testing stations may be disposed along the conveyor system, and the use of an X-Y-Z robotic arm and novel plate support bracket allows each of the samples in the wells to be input into the microfluidic network through a probe affixed to a microfluidic chip. A clamshell structure having a hinged lid can releasably support the chip while providing and/or accommodating the electrical, optical, structural, and other interface connections between the microfluidic device and the surrounding system.

Claims

1. A system for analyzing a plurality of samples, the system comprising:

a plurality of arrays, each array having a plurality of regions for holding the samples;

a robotic arm for translating the arrays sequentially along an array path;

an analysis station comprising at least one microfluidic device disposed off the array path, the microfluidic device having a sample input port, an analysis channel, and a detection point, the microfluidic device having at least one channel fluidly coupled to the sample input port with at least one channel cross-sectional dimension in a range from about 0.1 μ

m to about 500 μ

m; and

wherein the robotic arm is configured to sequentially aligns each region of each array with the input port of the microfluidic device.

2. The system of claim 1, further comprising a microfluidic device interface structure supporting the microfluidic device at a fixed position.

3. The system of claim 2, wherein the interface structure comprises a fixed base and a lid, the lid being pivotally coupled to the base so that the microfluidic device is removably restrainable therebetween, at least one of the lid and the base defining a window, and wherein an optical detection system is optically coupled to the channel system through the window for monitoring an optical characteristic of a reaction within the channel system.

4. The system of claim 2, wherein the interface structure further comprises at least one electrode for coupling an electrical potential source to fluid within the channel system.

5. The system of claim 1, wherein the arrays comprise plates and the regions comprise wells wherein a group of the wells on each plate are aligned along a first well alignment axis, and wherein the robotic arm can translate the plates with a first degree of freedom along the first well alignment axis to sequentially introduce samples from the group into the sample input port.

6. The system of claim 5, wherein the wells of each plate define an array having a second well alignment axis between a plurality of groups, and wherein the robotic arm can translate each plate with a second degree of freedom along the second well alignment axis to introduce samples from the groups into the sample input port.

7. The system of claim 5, wherein the robotic arm can move each plate horizontally along the first degree of freedom so that the wells are aligned sequentially with the sample input port, and can lift each plate so that the sample input port extends into the samples within the aligned well, the sample input port comprising a pipettor fluidly coupled to the channel system of the microfluidic device.

8. The system of claim 1, wherein the robotic arm has at least two degrees of freedom.

9. The system of claim 1, wherein the sample input port comprises a pipettor rigidly coupled to the microfluidic device and fluidly coupled to the channel system.

14. The system of claim 1, wherein the array path is at least partially linear.

15. The system of claim 1, wherein the array path is at least partially a loop.

10. A system for analyzing a plurality of samples, the system comprising:

a plurality of plates, each plate having an array of wells;

a robotic arm for moving the plates along a plate path;

at least one test station disposed along the plate path, the at least one test station comprising;

a microfluidic substrate having a sample input port, an analysis channel, and a detection point, the analysis channel disposed within the substrate and in fluid communication with the sample input port, the microfluidic substrate including at least one channel having a cross-sectional dimension in a range from about 0.1 μ

m to about 500 μ

m; and

wherein the robotic arm has at least two degrees of freedom and is configured to sequentially align the wells of each plate with the input port of the substrate.

11. The system of claim 10, wherein the sample input port comprises a pipettor rigidly coupled to the microfluidic device and fluidly coupled to the at least one channel.

12. A method for testing a plurality of samples, the method comprising:

arranging the samples in a plurality of regions disposed on at least one sample array;

transporting the at least one sample array along an array path using a robotic arm having at least two degrees of freedom;

removing the at least one array from the array path and sequentially aligning the regions of the array with a sample input port of a microfluidic device using the robotic arm so that the samples are transferred sequentially from the regions into the sample input port, the sample input port in fluid communication with an analysis channel disposed within the substrate, the microfluidic device including at least one channel having a cross-sectional dimension in a range from about 0.1 μ

m to about 500 μ

m; and

testing the samples using the analysis channel and a detection point disposed on or in the microfluidic device.

13. The method of claim 12, wherein testing the samples using the analysis channel comprises detecting a characteristic of the samples in the analysis channel of the microfluidic device.