Systems and devices for analysis of samples

• US 9,643,182 B2
• Filed: 11/26/2014
• Issued: 05/09/2017
• Est. Priority Date: 04/16/2010
• Status: Active Grant

• Current Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Original Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Inventors: Linder, Vincent, Steinmiller, David, Taylor, Jason
• Primary Examiner(s): HIXSON, CHRISTOPHER
• Application Number:
  US14/554,205
• Publication Number:
  US 20150086997A1
• Time in Patent Office: 895 Days
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2200/146 Employing pressure sensors
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/027 Digital display, e.g. LCD, LED
• CPC Class Codes: B01L 2300/04 Closures and closing means
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• 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 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2300/16 Surface properties and coatings
• CPC Class Codes: B01L 2300/168 Specific optical properties, e.g. reflective coatings
• CPC Class Codes: B01L 2300/1827 : using resistive heater
• CPC Class Codes: B01L 2300/1894 : Cooling means; Cryo cooling
• CPC Class Codes: B01L 2400/0475 : specific mechanical means and fluid pressure
• CPC Class Codes: B01L 2400/049 : vacuum
• CPC Class Codes: B01L 2400/0666 : Solenoid valves
• CPC Class Codes: B01L 2400/082 : Active control of flow resistance, e.g. flow controllers
• 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 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• 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: G01N 21/05 : Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/59 : Transmissivity G01N21/25 takes precedence
• CPC Class Codes: G01N 21/64 : Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/76 : Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 2201/02 : Mechanical
• CPC Class Codes: G01N 2201/0612 : Laser diodes
• CPC Class Codes: G01N 2201/062 : LED's
• CPC Class Codes: G01N 2201/0621 : Supply
• CPC Class Codes: G01N 2201/0697 : Pulsed lasers
• CPC Class Codes: G01N 2333/96433 : Serine endopeptidases (3.4.21)
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/57434 : of prostate
• CPC Class Codes: Y10T 137/0324 : With control of flow by a condition or characteristic of a fluid
• CPC Class Codes: Y10T 436/12 : Condition responsive control

Abstract

Systems and methods for analysis of samples, and in certain embodiments, microfluidic sample analyzers configured to receive a cassette containing a sample therein to perform an analysis of the sample are described. The microfluidic sample analyzers may be used to control fluid flow, mixing, and sample analysis in a variety of microfluidic systems such as microfluidic point-of-care diagnostic platforms. Advantageously, the microfluidic sample analyzers may be, in some embodiments, inexpensive, reduced in size compared to conventional bench top systems, and simple to use. Cassettes that can operate with the sample analyzers are also described.

Claims

1. A method of analyzing a microfluidic sample, the method comprising the steps of:

providing a microfluidic sample analyzer comprising a housing with an opening therein, wherein a cassette is contained in the opening in the housing and, wherein the cassette or a component of the cassette includes at least one channel with a fluid sample therein;

identifying information about the cassette with an identification reader positioned on or within the housing;

processing information input by a user into a user interface positioned within the housing of the sample analyzer;

pressurizing the at least one channel in the cassette with a pressure-control system positioned within the housing to move the sample through the at least one channel;

accumulating an opaque material on a portion of a surface of a channel within a first measurement zone of the cassette;

activating an optical system that passes light from a first light source positioning within the housing through the first measurement zone of the cassette;

detecting the amount of light transmission through the opaque material within the first measurement zone of the cassette with a first detector of the optical system positioned within the housing opposite the first light source; and

analyzing the sample in the cassette with a control system positioned within the housing which communicates with the identification reader, the user interface, the pressure-control system, and the optical system.

2. A method as in claim 1, comprising heating the cassette with a temperature regulating system positioned within the housing of the sample analyzer.

3. A method as in claim 1, wherein a fluid connector fluidically interconnects first and second unconnected channels of the cassette so as to cause fluid communication between the first and second channels.

4. A method as in claim 3, wherein, prior to first use of the cassette, at least one of the first and second channels contains a stored reagent, the cassette being sealed prior to first use so as to store the reagent in the cassette for at least one day.

5. A method as in claim 4, wherein the stored reagent is a liquid.

6. A method as in claim 4, wherein, prior to first use of the cassette, at least one of the first and second channels contains at least a first and a second fluid reagent which are separated by a third fluid substantially immiscible with both the first and second fluids.

7. A method as in claim 3, wherein the fluid sample is contained within the fluid connector.

8. A method as in claim 1, wherein the identifying information comprises identifying at least one of lot number, calibration information, and expiration date of the cassette.

9. A method as in claim 1, wherein the first measurement zone of the cassette includes a meandering channel including a plurality of segments, and wherein the optical system is positioned adjacent more than one segments of the meandering channel.

10. A method as in claim 9, wherein detecting comprises measuring a single signal through the more than one segments of the meandering channel.

11. A method as in claim 1, wherein the cassette includes a plurality of measurement zones fluidically connected in series, each measurement zone aligned with an optical system and a light source positioned within the housing, the method comprising flowing the fluid sample across each of the plurality of measurement zones and measuring light transmission through each of the plurality of measurement zones.

12. A method as in claim 1, comprising, during essentially the entire analysis, applying a substantially constant non-zero pressure drop between an inlet to the first measurement zone of the cassette and an outlet positioned downstream of the first measurement zone.

13. A method as in claim 1, wherein the analyzer comprises a plurality of light sources including at least a first light source and a second light source adjacent the first light source, wherein the first light source is configured to pass light through a first measurement zone of the cassette and the second light source is configured to pass light through a second region of the cassette adjacent the first measurement zone, the method comprising activating the first light source when the second light source is not activated, and not activating the second light source unless the first light source is deactivated.

14. A method as in claim 13, comprising activating the plurality of light sources sequentially with only one light source activated at a time.

15. A method as in claim 1, wherein the opaque material comprises silver.

16. A method as in claim 1, wherein the opaque material is formed by electroless deposition.

17. A method as in claim 1, wherein the opaque material is deposited by electroless deposition on a metal colloid.

18. A method as in claim 17, wherein the metal colloid comprises a gold-conjugated antibody.

19. A method as in claim 1, wherein the opaque material is formed by flowing a metal solution through the channel.

20. A method as in claim 1, comprising quantitatively determining the opacity of the opaque material.

21. A method as in claim 1, comprising absorbing a fluid in the cassette with an absorbent material contained in a liquid containment region in fluid communication with the first measurement zone.

22. A method as in claim 1, comprising absorbing substantially all liquids flowing in the cassette in a liquid containment region in fluid communication with the first measurement zone, while allowing any gases to escape from an outlet of the cassette.

23. A method as in claim 1, wherein the fluid sample comprises whole blood.

24. A method of analyzing a microfluidic sample, the method comprising the steps of:

providing a microfluidic sample analyzer comprising a housing with an opening therein, wherein a cassette is contained in the opening in the housing and, wherein the cassette or a component of the cassette includes at least one channel with a fluid sample therein;

identifying information about the cassette with an identification reader positioned on or within the housing;

processing information input by a user into a user interface positioned within the housing of the sample analyzer;

pressurizing the at least one channel in the cassette with a pressure-control system positioned within the housing to move the sample through the at least one channel;

activating an optical system comprising a plurality of light sources including at least a first light source and a second light source adjacent the first light source, wherein the first light source is configured to pass light through a first measurement zone of the cassette and the second light source is configured to pass light through a second region of the cassette adjacent the first measurement zone, the method comprising activating the first light source when the second light source is not activated, and not activating the second light source unless the first light source is deactivated;

detecting the amount of light transmission through the first measurement zone of the cassette with a first detector of the optical system positioned within the housing opposite the first light source; and

analyzing the sample in the cassette with a control system positioned within the housing which communicates with the identification reader, the user interface, the pressure-control system, and the optical system.

25. A method of analyzing a microfluidic sample, the method comprising the steps of:

providing a microfluidic sample analyzer comprising a housing with an opening therein, wherein a cassette is contained in the opening in the housing and, wherein the cassette or a component of the cassette includes at least one channel with a fluid sample therein;

identifying information about the cassette with an identification reader positioned on or within the housing;

processing information input by a user into a user interface positioned within the housing of the sample analyzer;

pressurizing the at least one channel in the cassette with a pressure-control system positioned within the housing to move the sample through the at least one channel;

accumulating an opaque material on a portion of a surface of a channel within the first measurement zone of the cassette, wherein the opaque material comprises a metal;

activating an optical system that passes light from a first light source positioning within the housing through the first measurement zone of the cassette;

detecting the amount of light transmission through the opaque material within the first measurement zone of the cassette with a first detector of the optical system positioned within the housing opposite the first light source; and

analyzing the sample in the cassette with a control system positioned within the housing which communicates with the identification reader, the user interface, the pressure-control system, and the optical system.