Systems and methods of sample processing and fluid control in a fluidic system

• US 8,741,230 B2
• Filed: 10/30/2006
• Issued: 06/03/2014
• Est. Priority Date: 03/24/2006
• Status: Active Grant

• Current Assignee: Golden Diagnostics Corporation (SoftBank Group Corp.)
• Original Assignee: Theranos Incorporated
• Inventors: Holmes, Elizabeth A., Roy, Shaunak, Gibbons, Ian, Qi, Shize Daniel, Ku, Edmond, Todd, Chris, Takahashi, Melissa, Johnson, Bruce, Fenton, Jeff, Moravick, Keith, Springborn, Uwe, Delacruz, Anthony
• Primary Examiner(s): Mui, Christine T
• Application Number:
  US11/554,509
• Publication Number:
  US 20070224084A1
• Time in Patent Office: 2,773 Days
• Field of Search: 422/100, 422/68.1, 422/50, 422/99
• US Class Current: 422/500
• CPC Class Codes: A61B 5/1411 by percutaneous method, e.g. by lancet
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150213 Venting means
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/150251 Collection chamber divided into at least two compartments, e.g. for division of samples injection syringes having more than one chamber A61M5/19; syringes for injection of two or more media A61M5/2448, A61M5/284; sample preparation for further analysis A61B5/150755
• CPC Class Codes: A61B 5/150274 Manufacture or production processes or steps for blood sampling devices
• CPC Class Codes: A61B 5/150282 for piercing elements, e.g. blade, lancet, canula, needle
• CPC Class Codes: A61B 5/150412 Pointed piercing elements, e.g. needles, lancets for piercing the skin blade-like piercing elements A61B5/150442
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/150755 Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
• CPC Class Codes: A61B 5/150778 having complementary physical shapes for indexing or registration purposes
• CPC Class Codes: A61B 5/150786 Optical identification systems, e.g. bar codes, colour codes
• CPC Class Codes: A61B 5/150854 long distance, e.g. between patient's home and doctor's office
• CPC Class Codes: A61B 5/150862 intermediate range, e.g. within room or building
• CPC Class Codes: A61B 5/15087 short range, e.g. between console and disposable using implanted devices A61B5/150877
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/15142 Devices intended for single use, i.e. disposable
• CPC Class Codes: A61B 5/157 : Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/412 : Detecting or monitoring sepsis
• CPC Class Codes: A61B 5/685 : Microneedles
• CPC Class Codes: G01N 2333/46 : from vertebrates
• CPC Class Codes: G01N 2333/91188 : transferring nitrogenous groups (2.6)
• CPC Class Codes: G01N 2800/52 : Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/5302 : Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/536 : with immune complex formed in liquid phase
• CPC Class Codes: G01N 33/573 : for enzymes or isoenzymes
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

This invention is in the field of medical devices. Specifically, the present invention provides portable medical devices that allow real-time detection of analytes from a biological fluid. The methods and devices are particularly useful for providing point-of-care testing for a variety of medical applications.

Claims

1. A fluidic device for detecting the presence or absence of an analyte in a bodily fluid from a subject, comprising a cartridge, said cartridge comprising a sample collection unit and an assay assembly, wherein:

(a) said sample collection unit is configured to;

(i) collect a sample of bodily fluid from said subject, and

(ii) deliver a predetermined portion of said sample to said assay assembly, and wherein said sample collection unit comprises;

(1) a sample collection well in fluid communication with a metering channel, configured so that a collected sample flows from said sample collection well into said metering channel;

(2) a metering element, wherein said metering element is adapted to close the fluid communication of said sample collection well to said metering channel, thereby isolating a specific volume of said sample in said metering channel, and wherein said metering element comprises a mechanically movable portion configured to be movable from an open position that permits fluid communication between the sample collection well and the metering channel to a closed position that does not provide fluid communication between the sample collection well and the metering channel; and

(3) a dilution chamber storing a diluent and being configured to be brought into and out of fluidic communication with said metering channel, said dilution chamber being coupled to the metering channel and defining at least one portion of a pathway for delivering the diluent to said assay assembly; and

(b) said assay assembly comprises at least one reaction site containing a reactant that reacts with said analyte to yield a detectable signal indicative of the presence of said analyte.

2. The fluidic device of claim 1, wherein said mechanically movable portion is a pin.

3. The fluidic device of claim 2, wherein said pin in said closed position blocks fluid flow through the metering channel.

4. The fluidic device of claim 2, wherein said pin is moved from said open position to said closed position by an actuator in a device in which the cartridge can be inserted.

5. The fluidic device of claim 1,

wherein said dilution chamber is configured to store a diluent and comprises a port for engaging a pressure means for transferring said diluent from the dilution chamber into the metering channel.

6. The fluidic device of claim 5, wherein said sample collection unit further comprises a mixing chamber in fluidic communication with said metering channel, said mixing chamber is configured to mix said predetermined portion of the sample with said diluent to yield a diluted sample.

7. The fluidic device of claim 6, wherein the mixing chamber comprises a movable mixing element that causes the mixing of said predetermined portion of the sample with the diluent.

8. The fluidic device of claim 6, wherein the sample collection unit further comprises a filter configured to filter the diluted sample before it is assayed.

9. The fluidic device of claim 7, wherein the movable mixing element is magnetically controlled.

10. The fluidic device of claim 1, wherein said predetermined portion of said sample is less than about 50 ul.

11. The fluidic device of claim 10, wherein said predetermined portion of said sample is less than about 20 ul.

12. The fluidic device of claim 11, wherein said predetermined portion of said sample is about 10 ul.

13. The fluidic device of claim 1, wherein said assay assembly is adapted to run an immunoassay.

14. The fluidic device of claim 13, wherein said assay assembly comprises at least one reagent chamber in fluidic communication with said at least one reaction site, wherein said reagent chamber is configured to store an assay reagent.

17. The fluidic device of claim 14, wherein the actuator element is adapted to be actuated by an actuator in a device in which the cartridge can be inserted.

18. The fluidic device of claim 17, wherein the actuator element is adapted to be mechanically actuated by said actuator.

19. The fluidic device of claim 14, wherein said second location has a larger cross section than said first location.

20. The fluidic device of claim 14, wherein said sealing element is substantially sphere shaped and said actuator element is substantially pin-shaped.

21. The fluidic device of claim 14, wherein said actuator element comprises a sealing member such that when said actuator element moves said sealing element the sealing member forms a substantially air tight seal such that said fluid can only flow through said channel.

22. The fluidic device of claim 21 wherein said actuator element is substantially pin shaped and said sealing member is an O-ring adapted to be placed around said actuator element.

27. A system for detecting an analyte in a bodily fluid from a subject, comprising:

a) the fluidic device of claim 1 or 15;

b) a reader assembly comprising a detection assembly for detecting said signal; and

c) a communication assembly for transmitting said signal to an external device.

28. The system of claim 27, wherein said assay assembly is adapted to run an assay based on an assay protocol transmitted from said external device.

29. The system of claim 28, wherein said assay protocol is transmitted wirelessly from said external device.

30. The system of claim 28, wherein said fluidic device further comprises an identifier to provide the identity of said fluidic device that is adapted to trigger the transmission of said assay protocol.

31. The system of claim 30 wherein said assay protocol varies depending on the identity of said fluidic device that is recognizable by an identifier detector.

32. The system of claim 27, wherein said predetermined portion of said sample is less than 50 ul.

33. The system of claim 32, wherein said predetermined portion of said sample is less than 20 ul.

34. The system of claim 33, wherein said predetermined portion of said sample is about 10 ul.

38. The system of claim 27, wherein the assay assembly comprises a waste chamber, said waste chamber comprising an optical quenching agent that reduces interfering signals generated from unbound reactants.

39. A method of detecting an analyte in a bodily fluid from a subject, comprising:

a) providing a fluidic device of claim 1;

b) metering a predetermined portion of said sample to be assayed in said sample collection unit;

c) allowing said predetermined portion of sample to react with assay reagents contained within said assay assembly to yield a signal indicative of the presence of said analyte in said sample; and

d) detecting said signal generated from said analyte collected in said sample of bodily fluid.

40. The method of claim 39, further comprising mixing said predetermined portion of said sample with a diluent in said fluidic device after the metering step.

41. The method of claim 40, wherein said mixing comprises diluting said predetermined portion of said sample with said diluent to yield a diluted sample.

42. The method of claim 41, further comprising filtering said diluted sample before allowing said predetermined portion of sample to react with assay reagents.

43. The method of claim 41, wherein said assay assembly comprises at least one reagent chamber and an actuatable valve assembly configured to control flow of the reagents out of said reagent chamber and into said at least one reaction site.

44. The method of claim 43, further comprising actuating said actuatable valve assembly to permit said reagent to flow from said reagent chamber to said reaction site.

45. The method of claim 44, wherein said actuatable valve assembly comprises an actuator pin and a sealing ball, and said actuating comprising actuating said actuator pin to displace said sealing ball.

46. The method of claim 39, further comprising the step of quantifying the amount of said analyte present in said bodily fluid after said detecting step.

47. The method of claim 46, further comprising the step of comparing the amount of said analyte present in said biologic fluid to a predetermined amount of said analyte.

48. The method of claim 39, wherein said fluidic device communicates data relating to said signal via a wireless transmitter to an external device.

49. The method of claim 39, wherein the analyte detected is indicative of at least one pharmacological parameter.

50. The method of claim 49, further comprising cross-referencing medical records of said subject with the at least one pharmacological parameter to assistant a clinician in providing an individualized medical treatment.

51. The fluidic device of claim 1 wherein the metering channel is coated with one or more of the following:

a surfactant, or an anti-coagulant solution.

52. The fluidic device of claim 5 wherein the dilution chamber is configured to be brought into and out of fluidic communication with the metering channel between the metering element and a stop junction of the metering channel.

15. A fluidic device for detecting an analyte in a bodily fluid from a subject, comprising:

a cartridge, said cartridge comprising

a sample collection unit, wherein said sample collection unit is configured to collect a sample of bodily fluid from said subject; and

an assay assembly, wherein said assay assembly comprises;

at least one reaction site in fluidic communication with said sample collection unit, said reaction site containing a reactant that reacts with said analyte to yield a signal indicative of the presence of said analyte;

at least one reagent chamber in fluidic communication with said at least one reaction site, wherein said reagent chamber is configured to store an assay reagent;

a fluidic channel connecting the reagent chamber with the reaction site; and

an actuatable valve assembly configured to control the flow of reagent through said fluidic channel, wherein the valve assembly comprises a sealing element and actuator element, wherein;

said channel comprises first and second locations, wherein the sealing element positioned in the first location obstructs the flow of fluid through the channel and the sealing element positioned in the second location allows the flow of fluid through the channel, providing fluidic communication between the sample collection unit and the reaction site; and

wherein the actuator element is adapted to move the sealing element from the first location to the second location; and

a dilution chamber storing a diluent and being configured to be brought into and out of fluidic communication with said channel, said dilution chamber being coupled to said channel and defining at least one portion of a pathway for delivering the diluent to said assay assembly.

16. The fluidic device of claim 15 wherein the actuator element is not adapted to move the sealing element from the second location to the first location.

23. The fluidic device of claim 15, wherein said assay assembly is adapted to run an immunoassay.

24. The fluidic device of claim 15, wherein said sample of bodily fluid is less than 50 ul.

25. The fluidic device of claim 24, wherein said sample of bodily fluid is less than 20 ul.

26. The fluidic device of claim 25, wherein said sample of bodily fluid is about 10 ul.

35. The system of claim 26, wherein said assay assembly is adapted to run an immunoassay.

36. The system of claim 26, wherein said system is adapted to monitor more than one pharmacological parameter useful for assessing efficacy and/or toxicity of a therapeutic agent.

37. The system of claim 26, wherein said system is adapted to automatically monitor patient compliance with a medical treatment involving a therapeutic agent.

53. The fluidic device of claim 15 wherein said dilution chamber comprises a port for engaging a pressure means for transferring said diluent from the dilution chamber into the channel.