Apparatus and methods for correcting for variable velocity in microfluidic systems

• US 6,703,205 B2
• Filed: 03/19/2002
• Issued: 03/09/2004
• 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: Parce, John Wallace, Sundberg, Steven A., Cohen, Claudia B., Chow, Andrea W., Kopf-Sill, Anne R.
• Primary Examiner(s): Chin, Christopher L.
• Assistant Examiner(s): Cook, Lisa V.
• Application Number:
  US10/102,149
• Publication Number:
  US 20020187513A1
• Time in Patent Office: 721 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, 422/82.01, 204/400, 204/403, 204/409, 204/412
• 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 of detecting the concentration of a product, rate of product formation, or the amount of the product produced by contacting at least a first and second component of a reaction comprising:

contacting the first and second reactant in a microfluidic channel, wherein the first reactant comprises a detectable label, thereby producing a product comprising the detectable label, which product has a different electrokinetic mobility than the first or second reactant, wherein flux is conserved in the microfluidic channel, whereby $\underset{h=1}{\overset{m}{\sum <br><br>}}<br><br>\text{\hspace{1em}<br><br>}<br><br>C_{R_h}<br><br>U_h=\underset{i=1}{\overset{n}{\sum <br><br>}}<br><br>\text{\hspace{1em}<br><br>}<br><br>C_{P_i}<br><br>U_i$

 

wherein C refers to mass concentration, R refers to the reactant species present in the microfluidic channel, P refers to product species produced in the microfluidic channel, U refers to velocity, m is the number of species prior to said contacting, and n is the number of species after said contacting;

flowing the product and any first or second reactant remaining in the channel subsequent to said contacting step past a detector, wherein the label on the first reactant and the label on the product comprise the same detectable moiety; and

,

determining at least one of;

concentration of the product, rate of product formation, or amount of product produced, wherein flux is conserved, whereby the sum of the concentration of the reactants and products times the respective velocity of reactants and products is constant.

2. The method of claim 1, wherein the detectable label is a fluorophore.

3. The method of claim 1, wherein the detectable label is not a fluorophore and the reaction is non-fluorogenic.

4. The method of claim 1, the method further comprising measuring or calculating the velocity of the first reactant, the second reactant, or the product.

5. The method of claim 1, wherein flux of the detectable label is conserved.

6. The method of claim 1, wherein the first or second reactant is periodically injected into the channel.

7. The method of claim 1, wherein the first reactant, the second reactant and the product are flowed continuously in the channel.

8. The method of claim 1, further comprising detecting phase shift of reactant and product waves.

9. The method of claim 1, wherein the first reactant, the second reactant or both the first and the second reactant is or are continuously flowed into the microchannel.

10. The method of claim 1, wherein the first reactant is continuously flowed into the microchannel and the second reactant is periodically injected into the microchannel from a side channel.

11. The method of claim 1, wherein the first reactant is continuously flowed into the microchannel and the second reactant is periodically injected into the microchannel from an intersecting side channel.