Dilutions in high throughput systems with a single vacuum source

• US 20050153459A1
• Filed: 12/06/2004
• Published: 07/14/2005
• Est. Priority Date: 08/25/1999
• Status: Abandoned Application

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Inventors: Chow, Andrea W., Kopf-Sill, Anne R., Sundberg, Steven A., Poglitsch, Claudia L.
• Application Number:
  US11/005,331
• Publication Number:
  US 20050153459A1
• Time in Patent Office: Days
• US Class Current: 436/183
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• 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 2400/049 vacuum
• CPC Class Codes: B01L 2400/084 Passive control of flow resistance
• 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 1/38 Diluting, dispersing or mixing samples
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/118339 with formation of a segmented stream
• CPC Class Codes: Y10T 436/25625 Dilution
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Flow rates in a microfluidic device are modulated after performing serial dilutions by flow reduction channels that draw fluid from the main channel, thus reducing the flow rate. The reduction in flow rate and/or use of smaller dimension channels allow reduced reagent consumption. In addition, multiple flow reduction channels are used for multiple concentration measurements and for performing multiple assays simultaneously on a single sample. Also included are microfluidic devices and integrated systems for performing assays using serial dilutions, single pressure sources, multiple concentration measurements, and reduced reagent consumption. Devices comprising flow reduction channels are also used to suppress pressure perturbations from spontaneous injection.

Claims

1. A method of suppressing pressure perturbations from spontaneous injection into a microfluidic device, the method comprising:

(i) dipping an open end of a capillary into a sample source, thereby drawing a sample from the sample source into the capillary, which capillary is fluidly coupled to a microfluidic device;

(ii) withdrawing the open end of the capillary from the sample source, wherein a first portion of the sample remains on the open end, which first portion has a surface tension, which surface tension exerts a first pressure on the capillary, thereby spontaneously injecting the first portion into the capillary;

(iii) flowing a second portion of the sample from the capillary into a main channel, which main channel intersects the capillary at a first intersection point; and

,

(iv) flowing a third portion of the sample through a shunt channel, which shunt channel intersects the main channel, thereby maintaining the first intersection point at a second pressure, which second pressure is different from the first pressure, thereby suppressing pressure perturbations in the main channel.

2. The method of claim 1, wherein the sample source comprises a microwell plate.

3. The method of claim 1, wherein the shunt channel intersects the main channel at the first intersection point or downstream of the first intersection point.

4. The method of claim 1, wherein the second pressure is greater than the first pressure.

5. The method of claim 1, wherein the second pressure is less than the first pressure.

6. The method of claim 1, wherein the first pressure is atmospheric pressure.

7. The method of claim 1, wherein step (iv) creates a pressure gradient between the open end of the capillary and the first intersection point.

8. The method of claim 1, further comprising applying a third pressure to the shunt channel, thereby altering the second pressure at the first intersection point.

9. The method of claim 8, wherein the third pressure is a negative or a positive pressure.