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

• US 9,588,109 B2
• Filed: 01/27/2016
• Issued: 03/07/2017
• 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:
  US15/007,585
• Publication Number:
  US 20160139138A1
• Time in Patent Office: 405 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 method of detecting at least two analytes present in a sample, the method comprising:

positioning a cartridge in an instrument, wherein the cartridge comprises;

a sample vessel, a plurality of reagent units, a plurality of assay units, and at least one pipette tip;

processing the sample to provide processed sample portions in selected assay units of the cartridge; and

removing at least one of said selected assay units from the cartridge and transporting said at least one of said selected assay units to a signal detector at a different location in the instrument;

wherein the cartridge contains all reagents and supplies for said detection of said at least two analytes.

2. The method of claim 1, wherein said cartridge is positioned in the instrument effective that an automated fluid transfer device of the instrument can engage at least one sample vessel, one of said reagent units, one of said assay units, or at least one pipette tip.

3. The method of claim 1, wherein at least one of said assay units comprises a pipette tip with a capture surface.

4. The method of claim 1, wherein at least one of said assay units comprises a pipette tip with a reaction site.

5. The method of claim 1, wherein the cartridge further comprises a housing for holding said reagent units and said assay units.

6. The method of claim 1, wherein the reagent units comprise instrument-operable containers that encapsulate liquid reagents.

7. The method of claim 1, wherein said reagents include liquid-phase and solid-phase reagents.

8. The method of claim 1 further comprising performing serial dilution on the sample, wherein a second diluted portion is formed from a first diluted portion.

9. The method of claim 1 further comprising using fingerstick blood from a single subject as the sample.

10. The method of claim 1 wherein the cartridge further comprises a housing, wherein a bottom of the housing is configured to collect waste liquids.

11. The method of claim 1 wherein the cartridge is configured to collect waste liquids after use that are transferred through a hole in a housing of the cartridge.

12. The method of claim 2, wherein said processing of the sample comprises transferring sample and diluent to one of the assay units using the fluid transfer device.

13. The method of claim 12, wherein the fluid transfer device is automated to follow a protocol associated with the cartridge to perform serial dilution of the sample.

14. The method of claim 12, wherein the fluid transfer device is automated to follow a protocol associated with a cartridge identifier that is associated with a subject.

15. The method of claim 1, further comprising expelling processed sample from the assay units and storing such expelled processed sample in the cartridge.

16. The method of claim 1, further comprising a touch-off absorber positioned on the cartridge in a plane different from at least some cavity openings on the cartridge.

17. The method of claim 14, further comprising using the fluid transfer device to perform an automated process carried out by a user-defined protocol.

18. The method of claim 14, wherein processing, diluting, removing, and detecting steps all occur within the instrument.

19. The method of claim 18, wherein the instrument is at a point-of-care (POC) location.

20. The method of claim 19, wherein said point-of-care (POC) location is a pharmacy.

21. The method of claim 19 further comprising sending data from the instrument in an encrypted format over a public network to a server comprising a network interface and a processor, wherein the server processes the data and then sends assay results over the public network to a user station display.

22. The method of claim 1, wherein said instrument comprises a translational stage for receiving said cartridge.

23. The method of claim 2, wherein said automated fluid transfer device comprises part of a bench-top instrument.

24. The method of claim 1, wherein said sample has a volume of between about 1 μ

L to about 100 μ

L.

25. The method of claim 1, further comprising obtaining said sample by lancing a subject to obtain a fingerstick blood sample.

26. The method of claim 2, wherein the automated fluid transfer device comprises a motor in communication with a programmable processor, wherein the motor can move a pipette head of the fluid transfer device based on a protocol from said programmable processor to change a sequence for transporting assay units and reagent units.

27. The method of claim 1, wherein the instrument is configured to automatically receive and process a whole blood sample to yield a plasma portion.

28. The method of claim 1, wherein cartridge identifier information is used to determine automated fluid transfer device movement.

29. The method of claim 1, wherein the cartridge further comprises a beads well.

30. The method of claim 1 wherein the sample vessel, the plurality of reagent units, the plurality of assay units, and the at least one pipette tip are all arranged in the cartridge in a two-dimensional configuration and not together in a single row.