MODULAR POINT-OF-CARE DEVICES, SYSTEMS, AND USES THEREOF

• US 20130274139A1
• Filed: 06/12/2013
• Published: 10/17/2013
• 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
• Granted Patent: US 8,697,377 B2
• Time in Patent Office: Days
• US Class Current: 506/9
• 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

1-78. -78. (canceled)

79. A method for transferring a reagent to an assay unit, comprising:

A) inserting a cartridge into an instrument, wherein the cartridge comprises i) an identifier, ii) an assay unit configured to run a chemical reaction that yields a signal indicative of an analyte, and iii) a reagent unit comprising a reagent, and wherein the instrument comprises a fluid transfer device comprising a programmable processor and a head configured to adhere to a pipette tip;

B) reading the identifier on the cartridge and transmitting the identity of the identifier from the instrument to an external device;

C) receiving by the programmable processor of the fluid transfer device a protocol from the external device, wherein the protocol is associated with the identifier and comprises instructions for transferring the reagent to the assay unit;

D) transferring by the fluid transfer device a selected volume of the reagent to the assay unit, wherein the selected volume is provided in the protocol, and wherein the fluid transfer device is operable to transfer different volumes of the reagent into the assay unit.

80. The method of claim 79, wherein the cartridge further comprises a bodily fluid sample.

81. The method of claim 80, further comprising transferring by the fluid transfer device a selected volume of bodily fluid sample to the assay unit, wherein the selected volume is provided in the protocol.

82. The method of claim 81, wherein the bodily fluid sample is diluted prior to being transferred to the assay unit.

83. The method of claim 81, further comprising prior to transferring the bodily fluid sample to the assay unit, processing the bodily fluid sample to remove red blood cells from the sample.

84. The method of claim 81, wherein the quantity of reagent transferred to the assay unit is selected based on the concentration of the analyte in the sample.

85. The method of claim 79, wherein the external device is configured to permit modification of the protocol by a user.

86. The method of claim 79, wherein the external device stores a plurality of protocols including the protocol associated with the identifier, and wherein the external device is configured to send to the instrument the protocol associated with the identifier from among the plurality of protocols.

87. The method of claim 79, further comprising engaging the assay unit with the head of the fluid transfer device and transporting by the fluid transfer device the assay unit from a first location to a second location in the instrument.

88. The method of claim 87, wherein the first location is the cartridge and the second location is a detection assembly.

89. The method of claim 80, wherein the assay unit is a first assay unit configured to run a chemical reaction that yields a signal indicative of a first analyte, wherein the cartridge further comprises a second assay unit configured to run a chemical reaction that yields a signal indicative of a second analyte, wherein the method further comprises transferring by the fluid transfer device a first selected volume of the bodily fluid sample to the first assay unit and transferring by the fluid transfer device a second selected volume of the bodily fluid to the second assay unit, wherein the first and second selected volumes are different volumes, and wherein the first and second selected volumes are provided in the protocol.

90. The method of claim 79, wherein the cartridge of step A) is a first cartridge, the method further comprising:

E) inserting a second cartridge into the instrument, wherein the second cartridge comprises i) an identifier, ii) an assay unit and iii) a reagent unit, and wherein the assay unit and reagent unit of the second cartridge contain the same contents as the assay unit and reagent unit of the first cartridge, respectively;

F) reading the identifier on the second cartridge and transmitting the identity of the identifier from the instrument to the external device;

G) receiving by the programmable processor of the fluid transfer device a protocol from the external device, wherein the protocol is associated with the identifier and comprises instructions for transferring the reagent of the second cartridge to the assay unit of the second cartridge;

H) based on the protocol of step G), transferring by the fluid transfer device a selected volume of the reagent in the second cartridge to the assay unit in the second cartridge.

91. The method of claim 90, wherein a different volume of reagent is transferred to the assay unit in the second cartridge than is transferred to the assay unit in the first cartridge.

92. The method of claim 91, wherein the identifier on the first cartridge and the identifier on the second cartridge are the same.

93. A system for automated transfer of a reagent to an assay unit, comprising:

A) a cartridge, comprising;

i) an identifier;

ii) an assay unit configured to run a chemical reaction that yields a signal indicative of an analyte; and

iii) a reagent unit comprising a reagent; and

B) an instrument, comprising a fluid transfer device containing a programmable processor and a head configured to adhere to a pipette tip; and

wherein the instrument is configured to receive the cartridge, to read the identifier on the cartridge, and to transmit the identity of the identifier to an external device, wherein the programmable processor of the fluid transfer device is configured to receive a protocol from the external device comprising instructions for transferring the reagent to the assay unit, and wherein the fluid transfer device is operable to transfer different volumes of the reagent into the assay unit and to, based on the protocol, transfer a selected volume of reagent to the assay unit.

94. The system of claim 93, wherein the external device is configured to permit modification of the protocol by a user.

95. The system of claim 93, wherein the assay unit is a first assay unit, the reagent unit is a first reagent unit, and the selected volume of the reagent is a first selected volume of the first reagent, wherein the cartridge further comprises a second assay unit and a second reagent unit comprising a second reagent, and wherein the fluid transfer device is operable to transfer a second selected volume of the second reagent to the second assay unit.

96. The system of claim 95, wherein the first selected volume and the second selected volumes are different quantities.

97. The system of claim 95, wherein the first assay unit comprises an antibody and the second assay unit comprises a nucleic acid probe.

98. The system of claim 93, wherein the reagent unit is a first reagent unit and the cartridge further comprises a second reagent unit, and the fluid transfer device is configured to separately engage the first reagent unit and the second reagent unit, the order of the engagement of the reagent units being based on the protocol received from the external device.

99. The system of claim 93, wherein the programmable processor is configured to execute multiple different protocols.

100. The system of claim 93, wherein the assay unit is engageable by the fluid transfer device and is movable by the fluid transfer device relative to the cartridge.

101. The system of claim 100, wherein the instrument further comprises a detection assembly, and wherein the assay unit is movable by the fluid transfer device from the cartridge to the detection assembly.

102. The system of claim 93, wherein the fluid transfer device is a multi-head pipette.

103. A method for automated dilution of a bodily fluid sample, comprising:

A) inserting a cartridge into an instrument, wherein the cartridge comprises i) an identifier, ii) a diluent unit comprising a diluent, and iii) a bodily fluid sample, and the instrument comprises a fluid transfer device comprising a programmable processor and a head configured to adhere to a pipette tip;

B) reading the identifier on the cartridge and transmitting the identity of the identifier from the instrument to an external device;

C) receiving by the programmable processor of the fluid transfer device a protocol from the external device, wherein the protocol is associated with the identifier and comprises instructions for the dilution of the bodily fluid sample;

D) combining by the fluid transfer device a selected volume of the diluent with a selected volume of the bodily fluid sample to generate a diluted bodily fluid sample, wherein the selected volume of the diluent and the selected volume of the bodily fluid sample are provided in the protocol, and wherein the fluid transfer device is operable to combine different volumes of the diluent with different volumes of the bodily fluid sample.

104. The method of claim 103, wherein the external device is configured to permit modification of the protocol by a user.

105. The method of claim 103, wherein the cartridge further comprises an assay unit, and the method further comprises transferring by the fluid transfer device at least a portion of the diluted bodily fluid sample to the assay unit.

106. The method of claim 103, wherein the selected volume of the diluent is a first selected volume of the diluent, the selected volume of the bodily fluid sample is a first selected volume of the bodily fluid sample, and the diluted bodily fluid sample is a first diluted bodily fluid sample, wherein the cartridge further comprises a first assay unit and a second assay unit, and wherein the method further comprises combining by the fluid transfer device a second selected volume of the diluent with a second selected volume of the bodily fluid sample to generate a second diluted bodily fluid sample, and transferring at least a portion of the first diluted bodily fluid sample to the first assay unit and at least a portion of the second diluted bodily fluid sample to the second assay unit.

107. The method of claim 106, wherein the first diluted bodily fluid sample and the second diluted bodily fluid sample contain different concentrations of bodily fluid sample.

108. The method of claim 106, wherein the volume of first diluted bodily fluid sample transferred to the first assay unit is different than the volume of second diluted bodily fluid sample transferred to the second assay unit.