Point-of-care fluidic systems and uses thereof

• US 7,635,594 B2
• Filed: 03/24/2006
• Issued: 12/22/2009
• Est. Priority Date: 05/09/2005
• Status: Active Grant

• Current Assignee: Golden Diagnostics Corporation (SoftBank Group Corp.)
• Original Assignee: Theranos Incorporated
• Inventors: Gibbons, Ian, Holmes, Elizabeth A., Roy, Shaunak, Wang, Chengwang, Howard, John, Qi, Shize Daniel, Kemp, Timothy M.
• Primary Examiner(s): Warden; Jill
• Assistant Examiner(s): TURK, NEIL N
• Application Number:
  US11/389,409
• Publication Number:
  US 20060264782A1
• Time in Patent Office: 1,369 Days
• Field of Search: 422/50, 422/56, 422/57, 422/58, 422/61, 422/63, 422/68.1, 422/81, 422/82, 422/82.01, 422/82.02, 422/82.05, 422/82.07, 422/82.08, 422/100, 422/101, 436/43, 436/63, 436/66, 436/95, 436/149, 436/164, 436/172, 436/174, 436/178, 436/180, 436/169, 204/193, 204/400, 204/403.01, 600/300, 600/347, 600/316, 600/319, 600/345, 600/365
• US Class Current: 436/50
• CPC Class Codes: A61B 5/1411 by percutaneous method, e.g. by lancet
• CPC Class Codes: A61B 5/1427 Multiple blood sampling, e.g. at periodic or pre-established intervals
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150099 by negative pressure, other than vacuum extraction into a syringe by pulling on the piston rod or into pre-evacuated tubes
• 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 5/150763 with identification means identification means for surgical instruments A61B90/90
• CPC Class Codes: A61B 5/150854 long distance, e.g. between patient's home and doctor's office
• 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 5/417 the bone marrow
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• 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 2300/087 : Multiple sequential chambers
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2300/0883 : Serpentine channels
• CPC Class Codes: B01L 2300/0887 : Laminated structure
• 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: G01N 21/76 : Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 2500/00 : Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/50 : Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q
• CPC Class Codes: G01N 33/53 : Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/5302 : Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/54386 : Analytical elements
• CPC Class Codes: G16H 40/63 : for local operation
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10T 436/10 : Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/115831 : Condition or time responsive
• CPC Class Codes: Y10T 436/12 : Condition responsive control
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]

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 two-way communication system for monitoring an analyte in a bodily fluid from a subject, comprising:

a) an external device configured to transmit a protocol to a reader assembly;

b) a fluidic device configured to be inserted into the reader assembly, said fluidic device comprising;

(i) a sample collection unit configured for collecting a sample of bodily fluid that contains an analyte;

(ii) an assay assembly containing reactants that react with said sample of bodily fluid based on the protocol transmitted from said external device to yield a detectable signal indicative of the concentration of said analyte present in said bodily fluid; and

(iii) an identifier that is configured to provide the identity of said fluidic device and is also configured to trigger the transmission of said protocol;

c) the reader assembly configured for two-way communication with the external device, said reader assembly comprising a programmable processor configured to receive said protocol from said external device, wherein said protocol in turn effects a reaction in said assay assembly for generating said detectable signal, wherein said reader further comprises a detection assembly for detecting said detectable signal, and a communication assembly for transmitting said detected signal to said external device, and wherein the external device is configured to (i) compare said concentration of said analyte detected with a reference concentration of said analyte stored in a database, and (ii) generate a subsequent reaction protocol based on said comparison in order to effect a subsequent reaction on a fluidic device for monitoring said analtye.

2. The system of claim 1, wherein said reader assembly is configured to receive said protocol wirelessly from said external device.

3. The system of claim 1, wherein said reader assembly comprises an identifier detector that detects said identifier.

4. The system of claim 1, wherein said sample collection unit collects a sample of bodily fluid which is less than about 500 ul.

6. The system of claim 1, wherein said reactants comprise immunoassay reagents immobilized within the assay assembly.

10. The system of claim 1, wherein said fluidic device is configured to detect a plurality of analytes and said fluidic device comprises immunoassay reagents for said plurality of analytes.

11. The system of claim 5 or 10, wherein the system is configured to detect a plurality of analytes that generate distinct signals, wherein the intensities of said distinct signals vary over a range of 3 orders of magnitude.

13. The system of claim 1 or 5, wherein the fluidic device further comprises a microneedle for obtaining the sample of said bodily fluid.

14. A method for detecting an analyte or a plurality of analytes in a bodily fluid of a subject, comprising:

a) providing a system of claim 1 or 5;

b) allowing a sample of bodily fluid to react with the reactants contained within said assay assembly to yield one or more detectable signal(s) indicative of the presence of said analyte or said plurality of analytes; and

c) detecting said detectable signal(s).

15. The method of claim 14, further comprising the step of quantifying the amount of said analyte or said plurality of analytes present in said bodily fluid.

16. The method of claim 15, further comprising the step of comparing the amount of said analyte or said plurality of analytes present in said bodily fluid to a predetermined amount of said analyte or said plurality of analytes.

17. The method of claim 16 further comprising the step of taking a medical action when the amount of said analyte or said plurality of analytes present in said bodily fluid is statistically different than said predetermined amount.

18. The method of claim 17, wherein the medical action comprises notifying a pharmacy that a prescription for such subject needs to be altered.

19. The method of claim 18, wherein the notification is electronically transmitted.

20. The method of claim 18, wherein the notification is wirelessly transmitted.

21. The method of claim 17, wherein the medical action comprises altering a subject'"'"'s dosage of a therapeutic agent.

22. The system of claim 1, wherein the fluidic device further comprises a dilution chamber containing diluent for diluting the sample of bodily fluid according to said protocol transmitted by the external device and received by the reader assembly.

23. The system of claim 1, wherein said protocol contains instructions to govern the extent of dilution taking place on said fluidic device.

24. The system of claim 1, wherein said analyte is representative of a pharmacodynamic or pharmacokinetic parameter.

25. The system of claim 1, wherein said external device is also configured to send instructions to the fluidic device to alter dosing of a pharmaceutical agent.

26. The system of claim 11, wherein the system is configured to perform a trend analysis based on said plurality of analytes.

27. The system of claim 1, further comprising a database for storing the comparison to yield a trend analysis, and wherein the subsequent reaction protocol is generated based on said trend analysis.

29. The system of claim 1, wherein the external device is further configured to send an alert, wherein the alert notifies the subject or a medical personnel based on said detectable signal.

30. The system of claim 1, wherein the external device is further configured to send an alert, wherein the alert notifies the subject or a third party based on the analyte concentration determined at the external device.

31. The system of claim 30, wherein the alert sent from the external device notifies the subject or the third party wirelessly.

5. A system for detecting a plurality of analytes of varying concentrations in a bodily fluid from a subject, comprising:

a) an external device configured to transmit a protocol to a reader assembly, wherein said protocol effects a plurality of reactions to be taking place in a fluidic device;

b) the fluidic device configured to be inserted into the reader assembly, said fluidic device comprising;

(i) a sample collection unit configured to collect a sample of said bodily fluid suspected to contain a plurality of analytes of varying concentrations;

(ii) a dilution chamber containing a diluent capable of diluting said sample of said bodily fluid;

(iii) an assay assembly containing a plurality of immunoassay reagents, each of which is permitted to react with a sample of said bodily fluid to generate a detectable signal within a range detectable by a reader assembly, and wherein said detectable signal is indicative of the concentration of an analyte of said plurality; and

(iv) an identifier that is configured to provide the identity of said fluidic device and is also configured to trigger the transmission of said protocol;

c) the reader assembly configured for two-way communication with the external device, said reader assembly comprising a programmable processor configured to receive said protocol from said external device, wherein said protocol from said external device determines degree of dilution performed with said diluent from said dilution chamber, and wherein said reader assembly comprises a detection assembly for detecting said detectable signals; and

d) a communication assembly for transmitting said detected signals to said external device.

7. The system of claim 5 or 6, wherein the immunoassay reagents are configured to detect a microorganism selected from the group consisting of bacterium, virus, fungus, and protozoa.

8. The system of claim 5 or 6, wherein the immunoassay reagents are configured to detect a polypeptide glycoprotein, polysaccharide, lipid, nucleic acid, and a combination thereof.

9. The system of claim 5 or 6, wherein the immunoassay reagents are configured to detect a member selected from the group consisting of drug, drug metabolite, biomarker indicative of a disease, tissue specific marker, and biomarker specific for a cell or cell type.

12. The system of claim 5 or 6, wherein the system detects luminescent signals from said plurality of reactions.

28. The system of claim 5, wherein the dilution chamber is configured to dilute the sample of said bodily fluid for each of the plurality of analytes depending on the analyte.

32. The system of claim 5, wherein a sample of said bodily fluid is prepared by way of dilution using the diluent based on the protocol transmitted from the external device to yield a detectable signal within a range detectable by the reader assembly.