Apparatus and method for correcting for variable velocity in microfluidic systems

• US 6,613,512 B1
• Filed: 12/05/2000
• Issued: 09/02/2003
• Est. Priority Date: 06/09/1997
• Status: Expired due to Term

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Inventors: Jaffe, Claudia B., Sunberg, Steven A., Chow, Andrea W., Parce, John Wallace, Kopf-Sill, Anne R.
• Primary Examiner(s): Chin, Christopher L.
• Assistant Examiner(s): COOK, LISA V
• Application Number:
  US09/445,638
• Time in Patent Office: 1,001 Days
• Field of Search: 435/4, 435/6, 435/7.9, 435/287.1, 435/287.2, 435/288.3, 435/288.4, 435/288.7, 435/810, 436/514, 436/518, 436/527, 436/531, 436/535, 436/149, 436/150, 436/151, 436/164, 436/165, 436/172, 436/805, 436/809, 422/55, 422/57, 422/58, 422/81, 422/82.01, 422/100, 422/101, 422/63, 204/400, 204/403, 204/409, 204/412, 204/604, 204/603
• US Class Current: 435/6.19
• 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 2219/0095 Control aspects
• CPC Class Codes: B01J 2219/0097 Optical sensors
• CPC Class Codes: B01J 2219/00995 Mathematical modeling
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• 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 3/50273 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 3/563 Joints or fittings in general F16L; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 27/447 using electrophoresis
• CPC Class Codes: G01N 27/44726 using specific dyes, markers or binding molecules
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 33/557 using kinetic measurement, i.e. time rate of progress of an antigen-antibody interaction
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10S 436/805 : Optical property
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays

Abstract

Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.

Claims

1. A method for determining the rate or extent of a reaction or assay in a microfluidic system, comprising:

converting a first reaction or assay component having a first velocity (U₁) into an assay product having a second velocity (U_p) in a microfluidic channel;

determining at least one velocity selected from the group consisting of U₁ and U_p;

determining the concentration of the first reaction component [C₁] or the concentration of the assay product [C_p] in a portion of the microfluidic channel; and

determining the rate or extent of the reaction or assay, wherein (U₁)[C₁]_converted=(U_p)[C_p] or (U₁)[C₁]=(U_p)[C_p].

2. The method of claim 1, wherein the first reaction or assay component is converted into the product by exposing the product to heat, light, acid, or base.

3. The method of claim 1, wherein the first reaction or assay component is converted into the product by contacting the first reaction or assay component with a second reaction or assay component.

4. The method of claim 1, the first reactant or product further comprising a detectable label.

5. The method of claim 1, further comprising determining the reaction rate constant (k) for the formation of the product.

6. The method of claim 1, further comprising the step of injecting one or more fluorescent dyes or other flow markers into the microfluidic channel to generate a flow profile versus time mask file.

7. The method of claim 1, further comprising the step of injecting one or more labeled size markers into the microfluidic channel to generate a fluorescence intensity versus time mask file.

8. The method of claim 1, further deconvolution of a complex signal with a time mask file.

9. The method of claim 1, further comprising baseline subtraction by injecting a series of blanks into the microfluidic channel in a control experiment to measure a time dependent baseline.

10. The method of claim 1, further comprising injecting at least one flow marker into the microfluidic channel, sampling signal from the flow marker and generating a flow profile versus time mask file.