Assay devices with integrated sample dilution and dilution verification and methods of using same

• US 9,766,232 B2
• Filed: 05/01/2015
• Issued: 09/19/2017
• Est. Priority Date: 12/03/2010
• Status: Active Grant

• Current Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Miller, Cary James, Davis, Graham, Zelin, Michael
• Primary Examiner(s): BROWN, MELANIE YU
• Application Number:
  US14/702,585
• Publication Number:
  US 20150233910A1
• Time in Patent Office: 872 Days
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/045 whereby the whole cover is slidable
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/126 Paper
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0672 Swellable plugs
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: G01N 21/25 Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
• CPC Class Codes: G01N 21/78 producing a change of colour
• CPC Class Codes: G01N 27/02 by investigating impedance
• CPC Class Codes: G01N 27/26 by investigating electrochemical variables; by using electrolysis or electrophoresis
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 27/3274 : Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 27/413 : Concentration cells using liquid electrolytes measuring currents or voltages in voltaic cells
• CPC Class Codes: G01N 27/49 : Systems involving the determination of the current at a single specific value, or small range of values, of applied voltage for producing selective measurement of one or more particular ionic species
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/76 : Human chorionic gonadotropin including luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone or their receptors

Abstract

The invention is to devices and method for rapid determination of analytes in liquid samples by various assays including immunoassays incorporating a sample dilution feature for forming a diluted sample for analysis. The devices and methods also include a dilution verification feature for verifying the degree of dilution of the diluted sample. The devices preferably are capable of being used in the point-of-care diagnostic field is provided.

Claims

1. A method of performing an assay for an analyte in a sample, said method comprising the steps of:

adding a dilution determinant marker to the sample;

determining the dilution determinant marker concentration in the sample;

introducing the sample into a sample chamber of a cartridge, wherein the sample chamber terminates in a sample extraction unit;

loading said extraction unit with said sample;

washing a portion of said sample from the extraction unit using a volume of diluent from a diluent conduit to form a diluted sample;

introducing said diluted sample to a reagent comprising a conjugate molecule;

measuring the dilution determinant marker concentration in said diluted sample;

comparing the dilution determinant marker concentration in the sample prior to introducing said sample into the sample chamber with the dilution determinant marker concentration in the portion of the sample washed from the extraction unit; and

analyzing said diluted sample for an analyte.

2. The method of claim 1, wherein the dilution determinant marker is selected from the group consisting of an electrochemical species, ferricyanide, ruthenium hexamine, a ferrocene, ferrocene monocarboxylic acid, an optical dye, fluorescein, an acridinium salt, and methylene blue.

3. The method of claim 1, wherein the dilution determinant marker concentration is measured using an electrochemical analysis system for amperometric measurements.

4. The method of claim 1, wherein the dilution determinant marker concentration is measured using a potentiometric sensor.

5. The method of claim 1, wherein the dilution determinant marker concentration is measured using a spectrophotometer.

6. The method of claim 1, wherein the dilution determinant marker is a different entity from that of the conjugate molecule.

7. The method of claim 1, further comprising calculating a dilution ratio based on the comparison of the dilution determinant marker concentration in the sample prior to introducing said sample into the sample chamber with the dilution determinant marker concentration in the portion of the sample washed from the extraction unit.

8. The method of claim 7, further comprising calculating a concentration of the analyte in the sample based on the analyzing of the diluted sample and the calculated dilution ratio.