Ultra high throughput microfluidic analytical systems and methods

• US 6,881,312 B2
• Filed: 12/13/2002
• Issued: 04/19/2005
• Est. Priority Date: 03/27/2000
• Status: Expired due to Term

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Inventors: Chow, Andrea W., Kennedy, Michael J., Jensen, Morten J., Spaid, Michael, Kennedy, Colin B., Kopf-Sill, Anne R., Jann, Peter C.
• Primary Examiner(s): KASTLER, SCOTT R
• Application Number:
  US10/319,045
• Publication Number:
  US 20030103207A1
• Time in Patent Office: 858 Days
• Field of Search: 204/603, 204/602, 204/453, 204/600
• US Class Current: 204/453
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00628 Ionic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01L 2200/023 adapted for different sizes of tubes, tips or container
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• 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 7/54 : using spatial temperature gradients
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 2021/0346 : Capillary cells; Microcells
• CPC Class Codes: G01N 2021/6419 : Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6421 : Measuring at two or more wavelengths
• CPC Class Codes: G01N 21/05 : Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/645 : Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 27/44721 : by optical means
• CPC Class Codes: G01N 27/44782 : of a plurality of samples
• CPC Class Codes: G01N 35/0099 : comprising robots or similar manipulators robots per se B25J

Abstract

Analytical systems and methods that use a modular interface structure for providing an interface between a sample substrate and an analytical unit, where the analytical unit typically has a particular interface arrangement for implementing various analytical and control functions. Using a number of variants for each module of the modular interface structure advantageously provides cost effective and efficient ways to perform numerous tests using a particular substrate or class of substrates with a particular analytical and control systems interface arrangement. Improved optical illumination and detection system for simultaneously analyzing reactions or conditions in multiple parallel microchannels are also provided. Increased throughput and improved emissions detection is provided by the present invention by simultaneously illuminating multiple parallel microchannels at a non-normal incidence using an excitation beam including multiple excitation frequencies, and simultaneously detecting emissions from the substances in the microchannels in a direction normal to the substrate using a detection module with multiple detectors.

Claims

1. A microfluidic system comprising:

a modular interface structure comprising at least first and second modules that provide an interface between an analytical instrument and a microscale substrate, wherein said first module comprises a heater interface which is positioned below the microscale substrate and is configured to heat fluid in one or more wells or a channels of microscale substrate; and

wherein said second module is spatially separated from said first module and is configured to interface with an analytical instrument and the first module, the second module comprising a fluid control interface which is configured to control the movement of fluid in one or more channels of the microscale substrate.

2. The system of claim 1, wherein the heater interface is positioned to simultaneously contact two or more microscale channels of the substrate.

3. The system of claim 1, wherein the heater interface is configured to contact the microscale substrate from an underside of the microscale substrate, while permitting one or more capillaries on the underside of the microscale substrate to project downward from the microscale substrate.

4. The system of claim 1, wherein the first module comprises a microscale substrate holder that supports the microscale substrate above the heater interface.

5. The system of claim 4, wherein the holder consists of one or more of:

a polymer, polymethylmethacrylate, polycarbonate, polytetrafluoroethylene, polyvinylchloride, polydimethylsiloxane, polysulfone, polystyrene, polymethylpentene, polypropylene, polyethylene, polyvinylidine, and acrylonitrile-butadiene-styrene copolymer.

6. The system of claim 1, further comprising an excitation or illumination source and a detector array.

7. The system of claim 6, wherein the illumination source includes two or more lasers.

8. The system of claim 7, wherein the illumination source comprises illumination optics that combine one or more output from two or more of the lasers.

9. The system of claim 1, further comprising a robotic armature for moving the microscale substrate.

10. The system of claim 1, further comprising an automatic refilling module configured to deliver fluid to the one or more wells.

11. The system of claim 1, wherein the second module comprises locating pins or holes which are configured to mate with corresponding holes or pins located on or within the first module.

12. The system of claim 1, wherein the second module comprises an electrical interface connector that is configured to mate with a corresponding electrical connector associated with the analytical instrument.

13. The system of claim 1, wherein the second module comprises a vacuum or pressure port for supplying one or more of a vacuum or pressure to one or more wells or channels of the microscale substrate.

14. The system of claim 1, wherein the second module comprises a window or opening defined therein to allow light to pass therethrough.

15. The system of claim 1, wherein the fluid control interface of the second module comprises a plurality of electrode pins which are configured to interface with a plurality of wells of the microscale substrate.