Method for determining diffusivity and molecular weight in a microfluidic device

• US 7,099,778 B2
• Filed: 12/30/2003
• Issued: 08/29/2006
• Est. Priority Date: 12/30/2003
• Status: Active Grant

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Inventors: Chien, Ring-Ling
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): SINES, BRIAN J
• Application Number:
  US10/747,066
• Publication Number:
  US 20050148093A1
• Time in Patent Office: 973 Days
• Field of Search: 422/50, 422/58, 422/68.1, 422/81, 422/82.05, 422/100, 422/101, 422/102, 422/103, 422/104, 422/110, 436/43, 436/52, 436/63, 436/164, 436/172, 73/10.1, 73/10.2, 702/1, 702/19, 702/22, 702/23, 702/27, 702/28, 702/29
• US Class Current: 702/23
• 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: G01N 13/00 Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects scanning-probe techniques or apparatus G01Q
• CPC Class Codes: G01N 2013/003 Diffusion; diffusivity between liquids
• CPC Class Codes: G01N 30/00 Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation G01N3/00, G01N5/00, G01N7/00, G01N9/00, G01N11/00, G01N13/00, G01N15/00, G01N17/00, G01N19/00, G01N21/00, G01N22/00, G01N23/00, G01N24/00, G01N25/00, G01N27/00, G01N29/00 take precedence
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The present invention is directed to a method for determining the molecular weight and diffusivity of a sample solute by providing a plus shaped microchannel network on a microfluidic chip, having at least four microchannels intersecting at a cross point; flowing a sample stream comprising a sample solute of unknown diffusivity and a blank stream from separate microchannels through the cross point and out to separate microchannels; creating a sample curve measuring the concentration of the sample solute that diffuses from the sample stream to the blank stream at the cross point while altering the flowrate of one of the blank stream or the sample stream; and determining a diffusion coefficient of the sample solute by extrapolating data from similar curves of at least two solutes having known molecular weights and/or diffusion coefficients created under similar conditions as those generated by the sample solute.

Claims

1. A method for determining the diffusivity of an unknown sample solute in a microchannel network, comprising the steps of:

providing an unknown sample solute stream;

providing a blank stream, wherein at least one of the unknown sample solute stream and the blank stream comprises a detectable first indicator;

allowing said unknown sample solute stream to contact said blank stream, such that a portion of said unknown sample solute in said unknown sample solute stream diffuses into said blank stream;

creating a curve that represents a concentration of said unknown sample solute that diffused into said blank stream as a function of flowrate of at least one of said unknown sample solute stream and said blank stream; and

extrapolating diffusivity of said unknown sample solute by comparing said curve to at least two curves created under similar conditions using solutes of known diffusivity.

2. The method for determining the diffusivity of claim 1, wherein said first indicator is a fluorescent indicator.

3. The method for determining the diffusivity of claim 1, wherein said concentration of said unknown solute that has diffused into said blank stream is represented by a measurement of the intensity of said first indicator exhibited in said blank stream.

4. The method for determining the diffusivity of claim 1, wherein said flowrate of one of said blank stream and said unknown sample solute stream is represented by a normalized measurement of a pressure differential used to control the flowrate of said one of said blank stream and unknown sample solute stream.

5. The method for determining the diffusivity of claim 1, wherein said blank stream and said unknown sample solute stream contact each other at a cross point, where four microchannels intersect.

6. The method for determining the diffusivity of claim 5, further comprising:

flowing said blank stream into which said unknown sample solute has diffused into a different microchannel than said sample solute stream.

7. The method for determining the diffusivity of claim 1, wherein said unknown sample solute stream includes a first standard solute of known diffusivity, said first standard sample solute is adhered to a second indicator, which is distinguishable from said first indicator.

8. The method for determining the diffusivity of claim 7, wherein said unknown sample solute stream includes a second standard solute of known diffusivity, said second standard solute is adhered to a third indicator, which is distinguishable from said first indicator and said second indicator.