Modular point-of-care devices, systems, and uses thereof

• US 8,088,593 B2
• Filed: 10/02/2008
• Issued: 01/03/2012
• Est. Priority Date: 10/02/2007
• Status: Active Grant

• Current Assignee: Labrador Diagnostics LLC (SoftBank Group Corp.)
• Original Assignee: Theranos Incorporated
• Inventors: Burd, Tammy, Gibbons, Ian, Holmes, Elizabeth A., Frenzel, Gary, Nugent, Anthony Joseph
• Primary Examiner(s): LAM, ANN Y
• Application Number:
  US12/244,723
• Publication Number:
  US 20090088336A1
• Time in Patent Office: 1,188 Days
• Field of Search: None
• US Class Current: 435/7.92
• CPC Class Codes: A61B 10/0038 Devices for taking faeces samples; Faecal examination devices anal receptacles A61F5/451
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 10/0051 for taking saliva or sputum samples devices for receiving spittle A61J9/00
• CPC Class Codes: A61B 10/0058 for taking sperm samples artificial insemination A61B17/43; for animals A61D19/021; genital receptacles for the male member A61F5/453; massage of the genitals A61H19/00
• CPC Class Codes: A61B 10/007 for taking urine samples measuring urological functions A61B5/20; genital receptacles A61F5/451; urinals for bed-ridden persons A61G9/006
• CPC Class Codes: A61B 10/02 Instruments for taking cell samples or for biopsy A61B10/0038 and A61B10/0045 take precedence; needle locating or guiding means A61B17/3403; samplers for enzymology or microbiology C12M1/26; sampling or preparing biological specimens G01N33/48
• CPC Class Codes: A61B 2010/0074 Vaginal or cervical secretions
• CPC Class Codes: A61B 2010/0077 Cerebrospinal fluid
• CPC Class Codes: A61B 5/15 Devices for taking samples of blood hypodermic syringes A61M5/178
• 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 5/151 Devices specially adapted for taking samples of capillary blood, e.g. by lancets , needles or blades
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00283 Reactor vessels with top opening
• CPC Class Codes: B01J 2219/00292 in the shape of pipette tips
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00371 comprising electrodes
• CPC Class Codes: B01J 2219/00385 Printing
• CPC Class Codes: B01J 2219/00466 in a slurry
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/005 : Beads
• CPC Class Codes: B01J 2219/00693 : Means for quality control
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• CPC Class Codes: B01L 2200/04 : Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/0689 : Sealing
• CPC Class Codes: B01L 2200/141 : Preventing contamination, tampering
• CPC Class Codes: B01L 2200/148 : Specific details about calibrations
• CPC Class Codes: B01L 2300/0654 : Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0829 : Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/1805 : Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/043 : magnetic forces
• CPC Class Codes: B01L 3/021 : Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/0262 : using touch-off at substrate or container
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/527 : for a plurality of reagents
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 7/5255 : by moving sample containers
• CPC Class Codes: B01L 9/543 : for disposable pipette tips, e.g. racks or cassettes
• CPC Class Codes: G01N 1/38 : Diluting, dispersing or mixing samples
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/00851 : process control parameters
• CPC Class Codes: G01N 2035/00881 : network configurations
• CPC Class Codes: G01N 2035/0097 : monitoring reactions as a function of time
• CPC Class Codes: G01N 2035/1032 : Dilution or aliquotting
• CPC Class Codes: G01N 2035/1034 : Transferring microquantities of liquid
• CPC Class Codes: G01N 2035/1048 : using the transfer device for another function
• CPC Class Codes: G01N 2333/4737 : C-reactive protein
• CPC Class Codes: G01N 2333/475 : Assays involving growth factors
• CPC Class Codes: G01N 2333/71 : for growth factors; for growth regulators
• CPC Class Codes: G01N 2333/912 : transferring phosphorus containing groups, e.g. kinases (2.7)
• CPC Class Codes: G01N 2333/91205 : Phosphotransferases in general
• CPC Class Codes: G01N 2333/9129 : Transferases for other substituted phosphate groups (2.7.8)
• CPC Class Codes: G01N 2800/26 : Infectious diseases, e.g. generalised sepsis
• CPC Class Codes: G01N 2800/60 : Complex ways of combining multiple protein biomarkers for diagnosis
• CPC Class Codes: G01N 33/5302 : Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/5304 : Reaction vessels, e.g. agglutination plates for solid-phase systems G01N33/543
• CPC Class Codes: G01N 33/54326 : Magnetic particles
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54386 : Analytical elements
• CPC Class Codes: G01N 33/56966 : Animal cells
• CPC Class Codes: G01N 33/57484 : involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
• CPC Class Codes: G01N 33/6803 : General methods of protein analysis not limited to specific proteins or families of proteins
• CPC Class Codes: G01N 33/94 : involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
• CPC Class Codes: G01N 35/00732 : Identification of carriers, materials or components in automatic analysers
• CPC Class Codes: G01N 35/00871 : Communications between instruments or with remote terminals
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/10 : Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices G01N35/0099 takes precedence
• CPC Class Codes: G01N 35/1065 : Multiple transfer devices
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array
• CPC Class Codes: G16H 10/40 : for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: Y10T 29/49826 : Assembling or joining
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

The present invention provides devices and systems for use at the point of care. The methods devices of the invention are directed toward automatic detection of analytes in a bodily fluid. The components of the device are modular to allow for flexibility and robustness of use with the disclosed methods for a variety of medical applications.

Claims

1. A device for detection of an analyte in a bodily fluid sample comprising:

a sample collection unit configured to receive the bodily fluid sample;

an array of assay units configured to receive a portion of the sample from the sample collection unit and configured to run a chemical reaction that yields a detectable signal indicative of the presence of the analyte in the sample; and

an array of reagent units configured to contain reagents for running the chemical reaction;

wherein an individual assay unit comprises an assay tip that is configured to receive the portion of the sample and the reagents, when the assay unit is moved into fluid communication with the reagent unit,

wherein the assay tip comprises a first opening on the first side of the tip and a second opening on a second side of the tip, wherein the first opening has a diameter greater than that of the second opening, and

wherein the assay tip comprises an interior surface having immobilized thereon reagents for detecting said analyte.

2. The device of claim 1, wherein the sample collection unit is configured to receive a volume of the bodily fluid sample of about 20 microliters or less.

3. The device of claim 1, wherein the sample collection unit is configured to receive a volume of the bodily fluid sample that is a single drop of blood.

4. The device of claim 1 further comprising a pretreatment unit configured to retrieve a portion of the bodily fluid sample for running the chemical reaction to detect the analyte.

5. The device of claim 4, wherein the bodily fluid is a whole blood sample and the portion is plasma.

6. The device of claim 4, wherein the sample collection unit is configured to receive a sample tip that collects at least a portion of the bodily fluid sample.

7. The device of claim 6, wherein the pretreatment unit or the individual assay unit is configured to receive the sample tip, which distributes the bodily fluid sample to said pretreatment unit or individual assay unit.

8. The device of claim 7, wherein the pretreatment unit is configured to receive a pretreatment tip that collects the sample from the pretreatment unit.

9. The device of claim 8, wherein the individual assay unit is configured to receive the sample tip or the pretreatment tip, which distributes the bodily fluid sample to the individual assay unit.

10. The device of claim 1, wherein the individual assay unit is movable from one location of the device to another.

11. The device of claim 10, wherein the individual reagent unit is configured to receive the movable assay unit in said device.

12. The device of claim 11, wherein the individual reagent unit is configured to receive within its cavity at least a portion of the movable assay tip in said device.

13. The device of claim 11 wherein the assay tip is configured to be moved from a first reagent unit to a second reagent unit.

14. The device of claim 11 wherein the second opening of the assay tip is configured to permit reagents to be distributed to the assay tip according to an aspiration- or pipette-type action provided to the assay tip.

15. The device of claim 1, wherein the individual assay unit comprises immunoassay reagents for running an immunoassay.

16. The device of claim 1, wherein the bodily fluid sample is a blood sample.

17. The device of claim 1, wherein the assay units and the reagent units are addressable to indicate the location of the units on the device.

18. The device of claim 17, wherein the individual reagent unit of the array is addressed to correspond to an individual assay unit in the device.

19. The device of claim 18, wherein the individual reagent unit and the individual assay unit are aligned in a column or in a row in the device.

20. The device of claim 1 further comprising a housing configured to receive the array of assay units and the array of reagent units.

21. A system for detection of an analyte in a bodily fluid sample comprising:

a. a device of claim 1; and

b. a detection assembly for detecting the detectable signal indicative of the presence or absence of the analyte.

22. The system of claim 21 further comprising a programmable mechanical device configured to move the individual assay unit from a first location to a second location.

23. The system of claim 21 further comprising a fluid transfer device.

24. The system of claim 23, wherein the fluid transfer device is a pipette.

25. The system of claim 24 wherein the pipette is an air-displacement pipette.

26. The system of claim 23, wherein the fluid transfer device is automated.

27. The system of claim 23, wherein the fluid transfer device comprises a plurality of heads, wherein an individual head of the plurality of heads is configured to engage the individual assay unit.

28. The system of claim 23, wherein the fluid transfer device comprises a programmable processor configured to direct fluid transfer of the bodily fluid sample from the sample collection unit and a reagent from an individual reagent unit to the individual assay unit.

29. The system of claim 28, wherein the configuration of the processor to direct fluid transfer effects a degree of dilution of the bodily fluid sample in the array of assay units to bring signals indicative of the analyte being detected within a detectable range, such that said analyte is detectable with said system.

30. The system of claim 21 further comprising a communication assembly for transmitting a protocol based on the analyte to be detected.

31. The system of claim 21 further comprising a heating block configured to receive the individual assay unit.

32. The system of claim 21, wherein the sample collection unit is operably linked to a magnetic block to effect regeneration of plasma from the bodily fluid, wherein the bodily fluid is a blood sample.

33. The device of claim 1, wherein the assay tip comprises an opening at one end from which sample or reagent is transferred in and out of the assay tip.

34. The device of claim 1, wherein the second opening of the assay tip is configured to permit a wash solution to enter and drain therethrough.

35. The device of claim 34, wherein the second opening of the assay tip is configured to permit the aspiration of wash solution into the assay tip.

36. A method of using automated immunoassay for detecting an analyte present in plasma portion of a whole blood sample, comprising:

a. providing a whole blood sample to the device of claim 1;

b. detecting a signal; and

c. transmitting result of (b) to an end user.

37. The method of claim 36, wherein the immunoassay is ELISA.

38. The method of claim 36, wherein the result is transmitted wirelessly.