FLUIDIC SYSTEMS COMPRISING AN INCUBATION CHANNEL, INCLUDING FLUIDIC SYSTEMS FORMED BY MOLDING

• US 20160207042A1
• Filed: 12/11/2015
• Published: 07/21/2016
• Est. Priority Date: 12/12/2014
• Status: Active Grant

• Current Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Original Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Inventors: Dirckx, Matthew, Taylor, Jason, Linder, Vincent
• Granted Patent: US 10,279,345 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/06 Fluid handling related problems
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/0858 Side walls
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• 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 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0694 vents used to stop and induce flow, backpressure valves
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/1484 : microstructural devices
• CPC Class Codes: G01N 2015/1006 : for cytology
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/00356 : Holding samples at elevated temperature (incubation)
• CPC Class Codes: G01N 2035/1034 : Transferring microquantities of liquid
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 35/00069 : whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Fluidic devices and methods involving incubation and/or mixing of assay components are provided. In some embodiments, a biological and/or chemical assay may be performed in fluidic device. The fluidic device may be designed to allow for controlled incubation and/or mixing of two or more assay components. In some such embodiments, the fluidic device may comprise an incubation channel having a relatively large cross-sectional dimension in fluid communication with a detection channel. The incubation channel may allow for adequate mixing and/or incubation of two or more assay components prior to analysis of the assay. In certain embodiments, the detection channel may be used to provide feedback on the extent of incubation and/or mixing. Based on the feedback, one or more component of the fluidic system may be regulated to allow the requisite degree of mixing and/or incubation to be achieved. In some embodiments, the controlled incubation and/or mixing of assay components in an incubation channel, as described herein, may allow for improved assay performance.

Claims

1. A method, comprising:

introducing a sample comprising a sample component into a sample collector;

connecting the sample connector to a sample inlet port of an article, wherein the article comprises first and second sides, wherein the first side comprises an incubation channel, and wherein the first side and/or second side comprises a detection channel in fluid communication with the incubation channel, and wherein the sample inlet port is in fluid communication with the incubation channel;

flowing, at a first flow rate, at least a portion of the sample from the sample collector to the incubation channel;

reducing the flow rate of the sample to a second flow rate, wherein the second flow rate is less than the first flow rate and/or is zero to allow incubation of the sample in the incubation channel;

modulating the flow rate of the sample to a third flow rate which is greater than or less than the second flow rate; and

flowing the sample through the detection channel.

5. A method as in claim 1, wherein the incubation channel has a cross-sectional area that is greater than a cross-sectional area of the detection channel.

6. A method as in claim 1, wherein the incubation channel has a cross-sectional area that is at least 0.008 mm², and the detection channel has a cross-sectional area that is less than 0.008 mm².

7. A method as in claim 1, wherein prior to the step of reducing the flow rate, none of the sample is flowed into the detection channel.

8. A method as in claim 1, wherein prior to the step of reducing the flow rate of the sample, at least a portion of the sample is flowed into the detection channel.

9. A method as in claim 1, comprising flowing at least a portion of the sample into a part, but not all, of the detection channel, detecting at least a portion of the sample at the detection channel, and then reducing the flow rate of the sample to the second flow rate.

10. A method as in claim 1, wherein the incubation channel has a width of at least about 100 microns and less than or equal to about 2 mm, a height of at least about 50 microns and less than or equal to about 2 mm, and a volume of at least 5 μ

L.

11. A method as in claim 1, wherein the detection channel has a width of at least about 50 microns and less than or equal to about 300 microns, and a height of at least about 10 microns and less than or equal to about 300 microns.

12. A method as in claim 1, wherein the detection channel comprises a reagent deposited on a surface of the detection channel.

13. A method as in claim 1, wherein a first intervening channel passes through the article and is positioned between the incubation channel and the detection channel.

21. A method as in claim 12, wherein the reagent is stored and sealed in the fluidic system.

22. A method as in claim 12, comprising contacting the sample with the reagent, wherein the contacting step occurs before or after the step of flowing at least a portion of the sample from the sample collector to the incubation channel.

23. A method as in claim 1, wherein a surface of the sample collector or a surface of the article comprises a reagent deposited thereon, and wherein the reagent is deposited on the surface by flowing a liquid containing the reagent across the surface and depositing the reagent during the step of flowing, at the first flow rate, at least a portion of the sample from the sample collector to the incubation channel.

33. A method as in claim 23, comprising mixing the sample component with the reagent in the sample in the incubation channel.

34. A method as in claim 23, comprising removing at least a portion of the reagent from the surface such that the reagent is dissolved or suspended in the sample, and wherein the step of removing at least a portion of the reagent from the surface takes place in the sample collector.

35. A method as in claim 23, comprising removing at least a portion of the reagent from the surface such that the reagent is dissolved or suspended in the sample, and wherein the step of removing at least a portion of the reagent from the surface takes place in the incubation channel.

63. A fluidic system as in claim 1, wherein the incubation channel and/or detection channel is formed in a material comprising a copolymer, and wherein at least one polymer component of the copolymer comprises reactive functional groups.

64. A fluidic system as in claim 63, wherein the reactive functional groups comprise one or more of anhydride-containing groups, maleimide-containing groups, amine-containing groups, aldehyde-containing groups, and acrylate-containing groups.

65. A method as claim 1, comprising performing the step of flowing, at the first flow rate, at least a portion of the sample from the sample collector to the incubation channel, followed by the step of reducing the flow rate of the sample to the second flow rate, followed by the step of modulating the flow rate of the sample to the third flow rate, followed by the step of flowing the sample through the detection channel.

2. A method, comprising:

introducing a sample comprising a sample component into a sample collector;

connecting the sample connector to a sample inlet port of an article, wherein the article comprises first and second sides, wherein the first side comprises an incubation channel, and wherein the first side and/or second side comprises a detection channel in fluid communication with the incubation channel, and wherein the sample inlet port is in fluid communication with the incubation channel;

flowing, at a first flow rate, at least a portion of the sample from the sample collector to the incubation channel;

flowing at least a portion of the sample into a part, but not all, of the detection channel;

reducing the flow rate of the sample to a second flow rate, wherein the second flow rate is less than the first flow rate and/or is zero;

modulating the flow rate of the sample to a third flow rate which is greater than or less than the second flow rate; and

flowing the sample through the detection channel.

3-4. -4. (canceled)

14-20. -20. (canceled)

24-32. -32. (canceled)

36-43. -43. (canceled)

44. A fluidic system comprising:

an article comprising first and second sides, wherein the first side comprises an incubation channel, and wherein the first side and/or second side comprises a detection channel in fluid communication with the incubation channel;

wherein the incubation channel has a width of at least about 100 microns and less than or equal to about 2 mm, a height of at least about 50 microns and less than or equal to about 2 mm, and a volume of at least 5 μ

L;

wherein the detection channel has a width of at least about 50 microns and less than or equal to about 300 microns, and a height of at least about 10 microns and less than or equal to about 300 microns, the detection channel comprising a reagent deposited on a surface of the detection channel;

wherein a ratio of heights of the incubation channel to the detection channel is at least 2;

1,

a sample inlet port in fluid communication with the incubation channel;

an outlet port in fluid communication with the detection channel; and

a sample collector adapted and arranged to be connected to the sample inlet port of the article.

45-62. -62. (canceled)