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

• US 8,822,167 B2
• Filed: 05/08/2013
• Issued: 09/02/2014
• 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:
  US13/889,674
• Publication Number:
  US 20130244898A1
• Time in Patent Office: 482 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 method of detecting at least two analytes of different analyte types from a small-volume biological sample within a short period of time, said method comprising:

Placing a cartridge in a reader assembly, said cartridge comprising a plurality of movable assay units, a plurality of movable reagent units, and a sample collection unit containing a small-volume biological sample, wherein at least one of said assay units and at least one of said reagent units are movable relative to each other, wherein individual movable reagent units are calibrated with reference to corresponding movable assay units before the movable reagent units are assembled on the cartridge, and wherein said reader assembly comprises a) a fluid transfer device, and b) a detection assembly configured to detect signals indicative of the presence of, or absence of, analytes of at least two different analyte types;

Transferring a first portion of said biological sample to a first movable assay unit, and transferring a second portion of said biological sample to a second movable assay unit, effective to divide said biological sample into at least a first portion and a second portion at an initial time;

Detecting a signal indicative of the presence of, or absence of, a first analyte of a first analyte type in said first portion of the biological sample in the first movable assay unit by a first time; and

Detecting a signal indicative of the presence of, or absence of, a second analyte of a second analyte type in said second portion of the biological sample in the second movable assay unit by a second time;

Wherein the period of time between said initial time and the later of said first time and of said second time comprises a short period of time;

Whereby analytes of at least two different analyte types are detected from a small-volume biological sample within a short period of time.

2. The method of claim 1, wherein said different analyte types comprise analyte types selected from protein analytes, nucleic acid analytes, organic analytes, and inorganic analytes.

3. The method of claim 1, wherein following said transferring, said first portion of said biological sample is contained within said first movable assay unit and is fluidically isolated from said second portion, and said second portion of said biological sample is contained within said second movable assay unit and is fluidically isolated from said first portion.

4. The method of claim 1, wherein said reader assembly comprises one or more of a system selected from the group consisting of:

a point of care system for detecting analytes in a biological sample;

a portable system for detecting analytes in a biological sample;

a desk-top system for detecting analytes in a biological sample; and

a bench-top system for detecting analytes in a biological sample.

5. The method of claim 1, wherein said short period of time comprises a period of time selected from the group of time periods consisting of:

a period of time of no more than one hour;

a period of time of less than 30 minutes;

a period of time of less than 15 minutes;

a period of time of less than 10 minutes; and

a period of time of less than 5 minutes.

6. The method of claim 1, further comprising mixing at least one biological sample portion with a reagent effective to run a chemical reaction within a movable assay unit, wherein said reagent is obtained from a movable reagent unit calibrated with reference to said movable assay unit.

7. The method of claim 1, wherein the volume of said small-volume biological sample comprises a volume selected from the group of volumes consisting of:

less than about 500 μ

L;

about 1 μ

L to 100 μ

L;

about 1 μ

L to 50 μ

L;

about 1 μ

L to 40 μ

L;

about 1 μ

L to 30 μ

L;

about 1 μ

L to 10 μ

L; and

about 1 μ

L to 3 μ

L.

8. The method of claim 1, wherein said detection assembly comprises an optical detector, and detecting a signal indicative of the presence of, or absence of, an analyte comprises optical detection.

9. The method of claim 1, wherein said biological sample is selected from the group consisting of blood, serum, plasma, saliva, urine, tears, gastric fluid, digestive fluid, bone marrow, cerebrospinal fluid, stool, semen, vaginal fluid, and liquid extracted from tissue.

10. The method of claim 1, wherein one or both of said transferring and said detecting are performed according to a protocol.

11. The method of claim 10, wherein said protocol may be altered by communication with a device or system.

12. The method of claim 1, wherein the order of detecting said first analyte and said second analyte may be altered by communication with another device or system.

13. The method of claim 1, wherein said detecting comprises the use of a nucleic acid probe, an antibody, or both.

14. The method of claim 1, wherein said cartridge comprises a calibration unit.

15. The method of claim 1, further comprising mixing a portion of said biological sample with a reagent, with a diluent, or with a reagent and a diluent, wherein said transferring, said mixing, or both said transferring and mixing comprises mechanical aspiration.

16. The method of claim 1, wherein at least one of said first movable assay unit and said second movable assay unit are movable within said cartridge.

17. The method of claim 1, further comprising moving said first movable assay unit or said second movable assay unit to a position near to said detection assembly.

18. The method of claim 1, wherein said detecting comprises transporting least a portion of said biological sample to a position near to said detection assembly, wherein said fluid transfer device comprises a pipette assembly, wherein said transporting comprises transport of said portion of said biological sample by said pipette assembly.

19. The method of claim 18, wherein said pipette assembly comprises an air-displacement pipette.

20. The method of claim 19, wherein said pipette assembly comprises a pipette head comprising a nozzle, wherein said nozzle is configured to engage a pipette tip.

21. The method of claim 1, further comprising diluting the biological sample in said movable assay units effective to bring signals indicative of at least two analytes in said biological sample within a detectable range, effective that said signals indicative of at least two analytes are detectable by said detection assembly.

22. The method of claim 1, wherein said detection assembly comprises a plurality of detectors, and detecting comprises use of a plurality of detectors.

23. The method of claim 8, wherein said optical detection comprises detecting a signal indicative of the presence of, or absence of, an analyte using a photodiode, an avalanche photodiode, a photomultiplier (PMT), a photon counting detector, a charge-coupled device, or a pin diode.

24. The method of claim 1, wherein one or more of said reader assembly, said fluid transfer device, and said detection assembly is configured to operate according to a protocol.

25. The method of claim 24, wherein said protocol is configured to be adjustable without requiring modification of the reader assembly, the fluid transfer device, or of the detection assembly.

26. The method of claim 1, further comprising one or both of transmitting information and receiving information, wherein said reader assembly comprises a communication assembly configured to transmit information, to receive information, or both.

27. The method of claim 1, wherein said transferring comprises transferring movable assay units, movable reagent units, and sample effective that a reagent for running a chemical reaction is brought into contact with at least a portion of the biological sample in a movable assay unit.

28. The method of claim 1, further comprising separation, dilution, lysing, processing, or retrieving of a portion of said biological sample by means of a pretreatment unit configured to separate, dilute, lyse, process, or retrieve a portion of said biological sample, or combinations thereof.