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

• US 9,121,851 B2
• Filed: 05/13/2013
• Issued: 09/01/2015
• 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:
  US13/893,258
• Publication Number:
  US 20130252320A1
• Time in Patent Office: 841 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 system for detection of a first analyte and a second analyte in a biological sample, comprising:

i) cartridge comprising a housing carrying a plurality of movable assay units configured to run chemical reactions on portions of said biological sample, wherein said chemical reactions are configured to yield detectable signals indicative of the presence or absence of said first analyte and said second analyte in the biological sample, wherein said housing is configured to carry a plurality of reagent units;

ii) a plurality of movable reagent units separate from said housing, said reagent units being filled with reagents for running said chemical reactions, wherein individual reagent units are calibrated with reference to corresponding assay units;

iii) a pipette assembly configured to transport aliquots of fluid and to transport assay units, said pipette assembly comprising pipette heads configured to engage said assay units; and

iv) a detection assembly for detecting said signals indicative of the presence or absence of said first and second analytes in the biological sample.

2. The system of claim 1, wherein said analytes are selected from the group of analyte types consisting of protein analytes, nucleic acid analytes, organic analytes, and inorganic analytes.

3. The system of claim 1 further comprising a sample collection unit configured to receive a biological sample, wherein said fluidic device a) is configured to engage said sample collection unit, or b) comprises said sample collection unit.

4. The system of claim 1, further comprising a reader assembly configured to engage said fluidic device.

5. The system of claim 1, comprising an assay unit configured to be moved into fluid communication with a reagent unit.

6. The system of claim 1, wherein said pipette assembly is configured to transfer a reagent effective to dilute at least a portion of a biological sample, to mix at least a portion of a biological sample with a reagent, to react with at least a portion of a biological sample with a reagent, or combinations thereof.

7. The system of claim 1, wherein said detection assembly comprises an optical detector.

8. The system of claim 7, wherein said optical detector comprises a photodiode, an avalanche photodiode, a photomultiplier (PMT), a photon counting detector, a charge-coupled device, or a pin diode.

9. The system of claim 1, wherein said detection assembly comprises a plurality of detectors.

10. The system of claim 1, wherein said detection assembly is configured to detect a signal from a nucleic acid assay, a signal from an immunoassay, or both.

11. The system of claim 1, wherein said system comprises a system selected from one or more 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.

12. The system 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.

13. The system of claim 1, wherein said biological sample has a volume selected from the group of volumes consisting of:

less than about 500 microliters (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.

14. The system of claim 1, wherein said pipette assembly is configured to transport at least a portion of a biological sample to said detection assembly.

15. The system of claim 1, further comprising a pretreatment unit configured to separate, dilute, process, or retrieve a portion of said biological sample, or combinations thereof.

16. The system of claim 1, wherein said pipette assembly comprises an air-displacement pipette.

17. The system of claim 1, comprising a pipette head comprising a nozzle.

18. The system of claim 17, wherein said nozzle is configured to engage a pipette tip.

19. The system of claim 1, wherein the pipette assembly is configured to operate according to a protocol.

20. The system of claim 19, wherein said protocol is configured to be adjustable without requiring modification of the system.

21. The system of claim 1, wherein the pipette assembly is configured for automated operation.

22. The system of claim 1, further comprising a communication assembly, wherein said communication assembly is configured to transmit information, to receive information, or both.

23. The system of claim 22, wherein operation of said system comprises operation according to a protocol, wherein said protocol is configured to incorporate information received by said communication assembly.

24. The system of claim 23, wherein said protocol is configured to be adjustable without requiring modification of the system.

25. The system of claim 1, wherein said detection assembly comprises a detectable range, and wherein said pipette assembly is configured to effect a degree of dilution of the biological sample in the array of assay units effective to bring signals indicative of at least two analytes in said biological sample within a detectable range, effective that said at least two analytes are detectable with said system.

26. The system of claim 1, comprising an assay unit comprising an assay tip that is configured to receive a portion of the sample and a reagent.

27. The system of claim 1, comprising assay units and reagent units configured to perform at least two assays in parallel.

28. The system of claim 1, comprising an assay unit and a reagent unit configured to move relative to each other effective that a reagent for running a chemical reaction is brought into contact with at least a portion of the biological sample in the assay unit.

29. The system of claim 1, wherein said fluidic device comprises a calibration unit.

30. The system of claim 1, wherein said biological sample has a volume selected from the group of volumes of about 1 microliters (μ

L) to 50 μ

L and about 1 μ

L to 10 μ

L.

31. A system for detection of a first analyte and a second analyte in a biological sample, comprising:

i) cartridge comprising a housing carrying an array of addressable assay units configured to run chemical reactions on portions of said biological sample, wherein said chemical reactions are configured to yield detectable signals indicative of the presence or absence of said first analyte and said second analyte in the biological sample, wherein said housing is configured to carry a plurality of reagent units;

ii) a plurality of reagent units separate from said housing, said reagent units being filled with reagents for running said chemical reactions, wherein individual reagent units are calibrated with reference to corresponding individual addressable assay units, and individual reagent units are addressed to correspond to individual addressable assay units;

iii) a pipette assembly configured to transport aliquots of fluid and to transport assay units, said pipette assembly comprising pipette heads configured to engage said assay units; and

iv) a detection assembly for detecting said signals indicative of the presence or absence of said first and second analytes in the biological sample.