System and Method for Regulating Flow in Fluidic Devices

• US 20110045599A1
• Filed: 12/31/2008
• Published: 02/24/2011
• Est. Priority Date: 12/31/2007
• Status: Active Grant

• Current Assignee: OI Corporation (Xylem, Inc.)
• Original Assignee: Oi Analytical
• Inventors: Ranger, Craig, Erickson, Gary L.
• Granted Patent: US 8,465,697 B2
• Time in Patent Office: Days
• US Class Current: 436/110
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/082 Active control of flow resistance, e.g. flow controllers
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: F04B 13/02 of two or more fluids at the same time
• CPC Class Codes: F04B 19/006 Micropumps F04B43/043 and F04B43/095 take precedence
• CPC Class Codes: F04B 49/106 Responsive to pumped volume
• 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 436/118339 with formation of a segmented stream
• CPC Class Codes: Y10T 436/173076 Nitrite or nitrate
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Disclosed are a system and method for regulating flow in an exemplary fluidic device comprising a fluidic stream carrying a transport medium, sample and one or more reagents for analysis and synthesis of reaction products. The flow rate of the fluidic stream is maintained constant by adjusting the flow rate of transport medium to compensate for the introduction of sample and reagents. An embodiment controls the flow rate of transport medium using a pump, a back pressure regulator, and a variable-sized orifice. Single and multiple channel embodiments are disclosed.

Claims

1. A system for regulating flow in a fluidic device, comprising:

one or more analytical streams comprising a transport medium and flowing through;

a pumping system and flow control module;

a sample introduction module;

a sample reaction module, the sample reaction module comprising a reaction device in a first analytical stream, the reaction device comprising an analyte produced by a reaction between a sample introduced by the sample introduction module into the first analytical stream and a reagent introduced by the sample reaction module into the first analytical stream;

a sample detection module, wherein the analyte is detected by a detector comprised in the sample detection module and the analyte has a constant flow at the detector;

wherein the pumping system and flow control module maintains a constant flow rate of the analyte at the detector by controlling the flow of transport medium in the first analytical stream to compensate for the sample and the reagent introduced into the first analytical stream.

2-14. -14. (canceled)

15. A system for regulating flow in a fluidic device, comprising:

One or more fluidic carrier streams, including a first carrier stream having a carrier flow rate;

a first injection means for introducing a first substance into the first carrier stream to make a first stream having a first stream flow rate;

a second injection means for introducing a second substance into the first stream to make a second stream having a second stream flow rate; and

a flow regulator coupled to the first carrier stream, the flow regulator operative to maintain the second stream flow rate at a constant value by adjusting the carrier flow rate to compensate for the introduction of the first substance into the first carrier stream and the second substance into the first stream.

18. The system of claim 15 comprising a plurality of fluidic carrier streams with independently regulated carrier flow rates.

24. The system of claim 15 wherein the first injection means comprises a non-peristaltic pump.

26. The system of claim 15 wherein the flow regulator comprises a fluidic flow controller.

28. The system of claim 26 wherein the fluidic flow controller comprises an orifice.

34. The system of claim 26 wherein the flow regulator further comprises a constant pressure fluid delivery system.

37. The system of claim 15 further comprising a reaction device through which the second stream flows.

40. The system of claim 37 further comprising a third injection means for introducing a third substance into the second stream downstream of the reaction device.

41. The system of claim 40 further comprising a master controller, the master controller operative to determine the timing and quantity of third substance introduced into the second stream.

42. The system of claim 41 wherein the master controller is further operative to time the introduction of the third substance into the second stream based on at least one of the following:

carrier flow rate, first stream flow rate, or second stream flow rate.

43. The system of claim 41 further comprising a user-configurable reaction device wherein the master controller is further operative to time the introduction of the third substance into the second stream based on a configuration of the reaction device.

44. The system of claim 15 further comprising:

a second carrier stream having a second carrier flow rate;

a third injection means for introducing third first substance into the second carrier stream to make a third stream;

a fourth injection means for introducing the second substance into the third stream to make a fourth stream having a fourth stream flow rate; and

a second carrier flow regulator coupled to the second carrier stream, the flow regulator operative to maintain the fourth stream flow rate at a constant value by adjusting the second carrier flow rate to compensate for the introduction of the first substance and the second substance into the second carrier stream and third stream.

16. The system of claim 15 wherein the first substance comprises a sample and the second substance comprises a reagent.

19. The system of claim 16 comprising a detector operative to detect a reaction between the sample and the reagent.

16-17. -17. (canceled)

20-23. -23. (canceled)

25. (canceled)

27. (canceled)

29-33. -33. (canceled)

35-36. -36. (canceled)

38-39. -39. (canceled)

45-51. -51. (canceled)

52. A sample and reagent addition system, comprising:

a carrier stream, wherein characteristics of the system allow location of components within the carrier stream in the system to be known;

a pump, wherein the pump is non-pulsatile, and wherein the pump continuously pumps the carrier stream;

a sample introduction device, wherein the sample introduction device introduces a sample to the carrier stream to provide a sample carrier stream; and

a reagent addition device to enable continuous or intermittent timed additions of reagents to the sample carrier stream at a desired location in the sample and reagent addition system.

53. A system for regulating fluid flow to a detector of a fluidic device, said system comprising:

a constant flow pump to deliver a transport medium to a manifold;

a back pressure regulator in fluid communication with said manifold arranged and designed to maintain pressure at said manifold at a constant;

a flow element in fluid communication with said manifold, said flow element designed to permit transport medium from said manifold to flow therethrough,

a valve disposed within said flow element to control said flow of transport medium therethrough;

said transport medium creating an analytical stream within said flow element;

a syringe pump to inject a volume of sample into said analytical stream of said flow element at a position downstream of said valve;

at least one reagent inlet for injecting a reagent into said analytical stream of said flow element;

at least one mixing volume disposed within said flow element at a position downstream of said at least one reagent inlet, said mixing volume arranged and designed to permit a reaction between said reagent and said sample to create a reaction product;

a detector to analyze said reaction product; and

a flow controller arranged and designed to control said valve, said syringe pump, and said reagent injection such that a constant flow of said analytical stream containing said reaction product is delivered to said detector.

54. A method for regulating flow in a fluidic device, comprising:

delivering a first carrier stream, said first carrier stream being fluidic and having a first carrier stream flow rate, said first carrier stream flow rate being substantially constant and initially substantially equal to a first target flow rate;

introducing a first substance into the first carrier stream to make a first stream having a first stream flow rate;

regulating the first carrier stream flow rate so that the first stream flow rate remains substantially constant;

introducing a second substance into the first stream to make a second stream having a second stream flow rate; and

further regulating the first carrier stream flow rate so that the second stream flow rate remains substantially constant.

55. The method of claim 54 wherein the first stream comprises a reagent and the second stream comprises a sample and further comprising detecting a reaction of the sample and the reagent.

80. The method of claim 54 further comprising delivering a second carrier stream, said second carrier stream being fluidic and having a second carrier stream flow rate, said second carrier stream flow rate being substantially constant and initially substantially equal to a second target flow rate;

introducing the first substance into the second carrier stream to make a third stream having a third stream flow rate;

regulating the second carrier stream flow rate so that the third stream flow rate remains substantially constant;

introducing the second substance into the third stream to make a fourth stream having a fourth stream flow rate; and

further regulating the second carrier stream flow rate so that the fourth stream flow rate remains substantially constant.

56-79. -79. (canceled)

81-85. -85. (canceled)