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

• US 9,581,588 B2
• Filed: 08/20/2015
• Issued: 02/28/2017
• Est. Priority Date: 10/02/2007
• Status: Active Grant

• Current Assignee: Labrador Diagnostics LLC (SoftBank Group Corp.)
• Original Assignee: Theranos Incorporated
• Inventors: Gibbons, Ian, Burd, Tammy, Holmes, Elizabeth A., Frenzel, Gary, Nugent, Anthony Joseph
• Primary Examiner(s): LAM, ANN Y
• Application Number:
  US14/831,734
• Publication Number:
  US 20150355169A1
• Time in Patent Office: 558 Days
• Field of Search: None
• US Class Current: 1/1
• 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 cartridge for detection of a plurality of analytes in a bodily fluid sample comprising:

a housing comprising a plurality of defined locations, each of which defined locations being configured to receive a unit or a tip, wherein said unit is selected from a sample collection unit, a reagent unit, and an assay unit;

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

a plurality of reagent units configured to contain reagents for running chemical reactions for detecting analytes; and

a plurality of assay units, each assay unit comprising an assay tip configured to engage with a fluid transfer device and having an interior surface defining an interior region configured to receive at least a portion of the sample from the sample collection unit and to receive reagent from a reagent unit, each assay tip comprising;

i) an opening configured to allow the transfer of fluids in and out of the assay tip;

ii) a clear and transparent portion configured to allow passage of an optical signal therethrough; and

iii) an interior surface having immobilized thereon reactants for a chemical reaction that yields a detectable optical signal indicative of the presence of an analyte in the sample;

wherein said assay units may be moved by said fluid transfer device to locations within said housing effective to place fluid within said sample collection unit or within reagent units into fluid communication with said interior regions of the assay units, and wherein sample, reagents, and reactants may contact each other effective to run chemical reactions and to provide optical signals for detecting said analytes, whereby said cartridge carries said sample collection unit, said plurality of reagent units, and said plurality of assay units in said plurality of defined locations of said housing.

2. The cartridge 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 cartridge 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 bodily fluid.

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

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

6. The cartridge of claim 4, further comprising a sample tip configured to collect at least a portion of the bodily fluid sample from said sample collection unit, and configured to distribute at least a portion of the bodily fluid sample to said pretreatment unit or said assay unit.

7. The cartridge of claim 6, further comprising a pretreatment tip configured to collect at least a portion of the sample from a pretreatment unit, wherein an assay unit is configured to receive sample from the sample tip or a pretreatment tip.

8. The cartridge of claim 1, wherein movement of an assay unit by said fluid transfer device effective to place said interior region of the assay unit into fluid communication with said sample collection unit or with a reagent unit comprises movement of an assay unit from defined one location of the cartridge to another defined location of the cartridge.

9. The cartridge of claim 8, wherein a reagent unit is configured to receive at least a portion of an assay tip.

10. The cartridge of claim 9 wherein an assay tip is configured to be moved from a first reagent unit to a second reagent unit.

11. The cartridge of claim 9 wherein an assay tip is configured to permit reagents to be distributed to the assay tip according to an aspiration-type or pipette-type action provided to the assay tip.

12. The cartridge of claim 1, wherein said reactants immobilized on said interior surface of an assay tip of an assay unit are selected from immunoassay reagents for running an immunoassay, nucleic acid assay reagents for running a nucleic acid assay, enzymes, substrates, and cofactors.

13. The cartridge of claim 1, wherein the bodily fluid sample comprises a bodily fluid selected from blood, serum, saliva, urine, gastric fluid, digestive fluid, tears, stool, semen, vaginal fluid, interstitial fluid, cerebrospinal fluid, and combinations thereof.

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

15. The cartridge of claim 14, wherein a reagent unit is addressed to correspond to an assay unit in the cartridge.

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

i) a cartridge of claim 1; and

ii) a detection assembly for detecting the detectable signal regarding an analyte.

17. The system of claim 16 further comprising a fluid transfer device configured to move an assay unit from a first location to a second location, and a communication assembly for transmitting a protocol based on the analyte to be detected.

18. The system of claim 17, wherein the fluid transfer device comprises a programmable mechanical device.

19. The system of claim 18, wherein the fluid transfer device is automated.

20. The system of claim 18, wherein the fluid transfer device comprises a plurality of heads, wherein said heads are configured to engage assay units.

21. The system of claim 18, wherein the fluid transfer device comprises a programmable processor configured to direct fluid transfer of the bodily fluid sample from the sample collection unit to said assay unit and to direct fluid transfer of a reagent from a reagent unit to the assay unit.

22. The system of claim 21, wherein the configuration of the processor to direct fluid transfer effects a degree of dilution of the bodily fluid sample in the assay unit to bring signals indicative of the analyte being detected within a detectable range, such that said analyte is detectable with said system.

23. The system of claim 16 further comprising a heating block configured to receive an assay unit.

24. The system of claim 16, wherein the sample collection unit is configured for operable linkage to a magnetic block for separation of a plasma portion from a blood sample.

25. The cartridge of claim 1, wherein the assay tip comprises at least one end, and comprises an opening at one end from which sample or reagent may be transferred in and out of the assay tip.

26. A method of using an automated immunoassay for detecting an analyte present in a bodily fluid sample, comprising:

i) providing a bodily fluid sample to the cartridge of claim 1;

ii) performing an automated immunoassay for detecting said analyte in said bodily fluid sample;

iii) detecting a signal provided by said automated immunoassay; and

iv) transmitting a result of (iii) to an end user.

27. The method of claim 26, wherein the immunoassay is an ELISA.

28. The method of claim 27, wherein the result is transmitted wirelessly.