Assay cartridges and methods for point of care instruments

• US 20070031283A1
• Filed: 06/23/2006
• Published: 02/08/2007
• Est. Priority Date: 06/23/2005
• Status: Abandoned Application

• Current Assignee: BioVeris Corporation (Roche Holding AG)
• Original Assignee: BioVeris Corporation (Roche Holding AG)
• Inventors: Davis, Charles, Miller, Jonathan, Liljestrand, John, Blankfard, Martin, Leland, Jonathan
• Application Number:
  US11/473,535
• Publication Number:
  US 20070031283A1
• Time in Patent Office: Days
• US Class Current: 422/58
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150213 Venting means
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/150251 Collection chamber divided into at least two compartments, e.g. for division of samples injection syringes having more than one chamber A61M5/19; syringes for injection of two or more media A61M5/2448, A61M5/284; sample preparation for further analysis A61B5/150755
• CPC Class Codes: A61B 5/150358 Strips for collecting blood, e.g. absorbent optical reagent test strips G01N21/8483; chemical reagent test strips G01N33/4875, G01N33/52
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• 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 5/150786 Optical identification systems, e.g. bar codes, colour codes
• CPC Class Codes: A61B 5/150793 Electrical or magnetic identification means
• CPC Class Codes: A61B 5/150862 intermediate range, e.g. within room or building
• CPC Class Codes: A61B 5/15087 short range, e.g. between console and disposable using implanted devices A61B5/150877
• CPC Class Codes: A61B 5/150893 by indicating if used, tampered with, unsterile or defective
• CPC Class Codes: A61B 5/15107 Piercing being assisted by a triggering mechanism
• CPC Class Codes: A61B 5/15117 comprising biased elements, resilient elements or a spring, e.g. a helical spring, leaf spring, or elastic strap
• CPC Class Codes: A61B 5/15142 Devices intended for single use, i.e. disposable
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: B01L 2200/027 : for microfluidic devices
• CPC Class Codes: B01L 2200/0636 : Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0647 : Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0668 : Trapping microscopic beads
• 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 2300/022 : Transponder chips
• CPC Class Codes: B01L 2300/0627 : Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0645 : Electrodes
• 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 2300/0864 : comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 : Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 : Multiple sequential chambers
• CPC Class Codes: B01L 2300/0874 : Three dimensional network
• 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 2300/1861 : using radiation
• CPC Class Codes: B01L 2300/1877 : using chemical reactions
• CPC Class Codes: B01L 2400/0406 : capillary forces
• CPC Class Codes: B01L 2400/0442 : thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/046 : Chemical or electrochemical formation of bubbles
• CPC Class Codes: B01L 2400/0481 : squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0633 : with moving parts
• CPC Class Codes: B01L 2400/0677 : phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 2400/0683 : mechanically breaking a wall or membrane within a channel or chamber
• CPC Class Codes: B01L 2400/0688 : surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 : characterised by venting arrangements
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502776 : specially adapted for focusing or laminating flows
• CPC Class Codes: B01L 7/00 : Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 2035/00108 : Test strips, e.g. paper
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/648 : using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/8483 : Investigating reagent band test-element handling not specific to a test method G01N33/4875; analytical elements specific to chemical analysis of biological material G01N33/52; autometer with reagent band G01N35/04
• CPC Class Codes: G01N 33/5002 : Partitioning blood components
• CPC Class Codes: G01N 33/5302 : Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/54326 : Magnetic particles
• CPC Class Codes: G01N 33/54346 : Nanoparticles
• CPC Class Codes: G01N 33/54386 : Analytical elements
• CPC Class Codes: G01N 33/582 : with fluorescent label
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Devices and methods are provided for performing a test to detect and/or quantify the presence of an analyte of interest within a sample using a portable instrument.

Claims

1. An assay cartridge comprising:

one or more incubation zones comprising at least one binding reagent specific for an analyte of interest and at least one labeled molecule comprising a label;

a sample collection system comprising at least one of a needle and a needle-pierceable membrane; and

a fluidic architecture that connects a sample entering the cartridge through the sample collection system to the incubation zone.

4. The cartridge of claim 1, wherein the cartridge comprises a separation filter located fluidically between the sample collection system and the incubation zone.

8. The cartridge of claim 4, wherein the separation filter is an asymmetric pore membrane blood separation filter.

9. The cartridge of claim 4, further comprising a storage zone, wherein the storage zone is fluidically located between the filter and the incubation zone.

10. The cartridge of claim 9, wherein the sample collection system, the separation filter, and the storage zone are configured so that a sample donor'"'"'s heart can generate at least part of the pressure that causes a blood sample from the sample donor to flow into the cartridge and plasma to flow from the separation filter into the storage zone.

21. The cartridge of claim 1, further comprising a plurality of magnetizable capture beads having diameters ranging from about 0.08 μ

m to about 10 μ

m.

24. The cartridge of claim 1, wherein each incubation zone is operatively connected to at least one measurement zone, and wherein each measurement zone is operatively connected to only one incubation zone.

25. The cartridge of claim 24, wherein the cartridge comprises a plurality of incubation zones.

161. The cartridge of any of claims 1, 59, 84, 107, or 134, wherein the incubation zone comprises a dry composition comprising:

a binding reagent for an analyte of interest;

a labeled molecule comprising a label; and

a plurality of magnetizable capture beads;

wherein the dry composition occupies at least 10% of the incubation zone.

2-3. -3. (canceled)

5-7. -7. (canceled)

11-20. -20. (canceled)

22-23. -23. (canceled)

26-28. -28. (canceled)

29. An assay cartridge comprising

one or more binding reagents for an analyte of interest;

one or more labeled molecules comprising a label; and

one or more incubation zones comprising a dry composition comprising a plurality of magnetizable capture beads;

wherein the dry composition occupies about 10% or more of the incubation zone.

31. The cartridge of claim 29, wherein the dry composition occupies about 50% or more of the incubation zone.

34. The cartridge of claim 29, wherein the capture beads range from about 10 μ

m in diameter to about 0.08 μ

m in diameter.

37. An instrument adapted to use the cartridge of claim 29, wherein the instrument comprises a magnetic field source and excludes an agitation mechanism for the beads.

38. The cartridge of claim 29, wherein the dry composition comprises the binding reagent and the labeled molecule.

39. The cartridge of claim 38, wherein the cartridge comprises a sample entry zone fluidically connectable to said incubation zone and a separation filter located fluidically between the sample entry zone and the incubation zone.

48. The cartridge of claim 29, wherein the label comprises a fluorophore.

51. The cartridge of claim 48, wherein the label has a Stoke'"'"'s shift of about 50 nm or more.

30. (canceled)

32-33. -33. (canceled)

35-36. -36. (canceled)

40-47. -47. (canceled)

49-50. -50. (canceled)

52-58. -58. (canceled)

59. An assay cartridge comprising:

one or more incubation zones comprising at least one binding reagent for an analyte of interest, at least one labeled molecule comprising a label, and a plurality of magnetizable capture beads;

one or more measurement zones comprising gas and fluidically connectable to said incubation zone;

a liquid reagent storage zone fluidically connectable to said measurement zone;

a sample entry zone fluidically connectable to said incubation zone;

a capillary stop positioned fluidically between the incubation zone and the measurement zone, said stop operative to impede liquid from going from incubation zone into the measurement zone when the measurement zone comprises gas;

a position on which a magnet external to the cartridge can be placed, so that the length of an imaginary straight line extending from a fixed point in the incubation zone to a fixed point at the position is about 20 mm or less, and wherein the imaginary straight line intersects the measurement zone.

60. The cartridge of claim 59 wherein the length is about 4 mm or less.

61. The cartridge of claim 59 wherein the cartridge further comprises a separation filter located fluidically between the sample entry zone and the incubation zone.

66. The cartridge of claim 59, comprising binding reagents specific for a total of at least 2 different analytes of interest.

79. The cartridge of claim 59, wherein each incubation zone is operatively connected to at least one measurement zone, and wherein each measurement zone is operatively connected to only one incubation zone.

80. The cartridge of claim 79, wherein the cartridge comprises a plurality of incubation zones.

81. The cartridge of claim 80, wherein the cartridge comprises fluidic passageways connecting the incubation zones, and further wherein the fluidic passageways are configured so that binding reagents in one incubation zone can not be diffusively transported to another incubation zone in less than about 20 minutes.

167. The cartridge of claim 59, wherein the incubation zone comprises an assay-performance-substance for one of the one or more analytes of interest comprising a label, a non-magnetizable bead having a diameter ranging from about 5 nm to about 10 μ

m, and a binding reagent for said analyte;

wherein the plurality of magnetizable capture beads have a diameter ranging from about 0.08 μ

m to about 10 μ

m; and

a plurality of magnetizable separation beads not capable of specifically binding with the analyte and/or said assay-performance-substance, wherein the separation beads have a diameter ranging from about 1 nm to about 20 nm.

168. The cartridge of claim 59, further comprising:

a filter fluidically connectable to the sample entry zone, said filter located so that filtrate operatively formed from a sample contacting the filter via the sample entry zone enters space fluidically connectable to a storage zone; and

a sample flow control apparatus that does not prevent a liquid sample from going from the sample entry zone through the filter into the storage zone and is externally controllable to stop or allow the flow of sample from the storage zone to the incubation zone.

172. The cartridge of claim 168, wherein the incubation zone comprises a dry composition comprising the binding reagent for an analyte of interest;

the labeled molecule comprising a label; and

the plurality of magnetizable capture beads;

wherein the dry composition occupies at least about 10% of the incubation zone.

177. The cartridge of claim 172, wherein the sample entry zone comprises a sample collection system comprising at least one of a needle and a needle- pierceable membrane through which a sample can operatively enter the cartridge.

62-65. -65. (canceled)

67-78. -78. (canceled)

82-83. -83. (canceled)

84. An assay cartridge comprising an incubation zone comprising:

an assay-performance-substance for one of the one or more analytes of interest comprising a label, a non-magnetizable bead having a diameter ranging from about 5 nm to about 10 μ

m, and at least one component chosen from an added analyte of interest, an added analog of said analyte, a binding reagent of said analyte or said analog, or a reactive component capable of binding with any of the foregoing;

a plurality of magnetizable capture beads capable of binding with the analyte and/or said assay-performance-substance, wherein the capture beads have a diameter ranging from about 0.08 μ

m to about 10 μ

m; and

a plurality of magnetizable separation beads not capable of binding with the analyte and/or said assay-performance-substance, wherein the separation beads have a diameter ranging from about 1 nm to about 20 nm.

85. The cartridge of claim 84, wherein the cartridge comprises a sample entry zone fluidically connectable to said incubation zone and a filter located fluidically between the sample entry zone and the incubation zone.

90. The cartridge of claim 84, comprising binding reagents specific for a total of at least 2 different analytes of interest.

86-89. -89. (canceled)

91-106. -106. (canceled)

107. An assay cartridge comprising:

one or more incubation zones comprising at least one binding reagent for an analyte of interest;

one or more storage zones fluidically connectable to said incubation zone;

a sample entry zone fluidically connectable to a separation filter, said separation filter located so that filtrate operatively formed from a sample contacting the separation filter via the sample entry zone enters space fluidically connectable to said storage zone; and

a sample flow control apparatus that does not prevent a liquid sample from going from the sample entry zone through the filter into the storage zone, and is externally controllable to stop or allow the flow of sample from the storage zone to the incubation zone.

108. The cartridge of claim 107, wherein the sample flow control apparatus comprises:

a vent configured to allow the passage of gas but not liquid, said vent located fluidically between the storage zone and the incubation zone; and

an externally controllable valve operative to stop or allow the flow of fluid, said valve located fluidically between the storage zone and the incubation zone.

109. The cartridge of claim 107, wherein the sample flow control apparatus comprises:

a vent configured to allow the passage of gas but not liquid, said vent located fluidically between the storage zone and the incubation zone; and

an externally controllable first valve operative to stop or allow the flow of fluid, said first valve located operatively downstream of the incubation zone.

129. The cartridge of claim 107, wherein each incubation zone is operatively connected to at least one measurement zone, and wherein each measurement zone is operatively connected to only one incubation zone.

130. The cartridge of claim 129, wherein the cartridge comprises a plurality of incubation zones.

166. The cartridge of any of claims 59 or 107, wherein the sample entry zone comprises a sample collection system comprising at least one of a needle and a needle-pierceable membrane through which a sample can operatively enter the cartridge.

179. The cartridge of claim 107, wherein the sample entry zone comprises a sample collection system comprising at least one of a needle and a needle-pierceable membrane through which a sample can operatively enter the cartridge;

wherein the incubation zone comprises a dry composition comprising

the binding reagent for an analyte of interest; and

the plurality of magnetizable capture beads; and

wherein the dry composition occupies at least 10% of the incubation zone.

184. The cartridge of claim 107, further comprising

an inlet passageway operatively downstream of the incubation zone;

a first outlet passageway operatively downstream of the inlet passageway comprising a measurement zone; and

a gas-filled second outlet passageway operatively downstream of the inlet passageway, said second outlet passageway comprising a vent configured to allow the passage of air but not liquid, said vent located operatively downstream of the junction between the inlet passageway and the second outlet passageway.

110. The cartridge of 109, wherein the sample flow control apparatus further comprises an externally controllable second valve operative to stop or allow the flow of fluid, said second valve located fluidically between the sample entry zone and the sample storage zone.

111-128. -128. (canceled)

131-133. -133. (canceled)

134. An assay cartridge comprising:

an incubation zone comprising binding reagents for an analyte of interest;

a inlet passageway operatively downstream of the incubation zone;

a first outlet passageway operatively downstream of the inlet passageway comprising a measurement zone; and

a gas-filled second outlet passageway operatively downstream of the inlet passageway, said second outlet passageway comprising a vent configured to allow the passage of air but not liquid, said vent located operatively downstream of the junction between the inlet passageway and the second outlet passageway.

135. The cartridge of claim 134, further comprising:

a sample entry zone fluidically connectable to a separation filter;

said separation filter located so that filtrate operatively formed from said separation filter enters a space fluidically connectable to the incubation zone.

156. The cartridge of claim 134, further comprising one or more incubation zones;

wherein each incubation zone is operatively connected to at least one measurement zone, and wherein each measurement zone is operatively connected to only one incubation zone.

178. The cartridge of any of claims 84 or 134, further comprising a sample collection system comprising at least one of a needle and a needle-pierceable membrane;

and a fluidic distribution system that connects a sample entering the cartridge through the sample collection system to the incubation zone.

136-155. -155. (canceled)

157-160. -160. (canceled)

162-165. -165. (canceled)

169-171. -171. (canceled)

173-176. -176. (canceled)

180-183. -183. (canceled)

185. (canceled)

186. An assay cartridge comprising an opaque surface operative to complete a light tight enclosure in an instrument comprising a light detector.

187. The cartridge of claim 186, wherein the instrument is portable.

188. A method for detecting the presence of one or more analytes of interest in a sample, comprising:

obtaining a sample using a sample collection system comprising at least one of needle and a needle-pierceable membrane and being adapted to connect to a cartridge adapted to store the sample;

inserting the cartridge into a testing instrument; and

performing a test to detect the presence of the analyte of interest in the sample.

189. The method of claim 188, wherein the instrument is portable.

190. A method of generating plasma from an animal comprising a cardiovascular system in an assay cartridge, the method comprising:

creating a fluidic connection between a vessel in the animal'"'"'s cardiovascular system and a blood separation filter, wherein the filter is fluidically connected to the assay cartridge; and

collecting plasma in the assay cartridge.

191. The method of claim 190, wherein the animal is a human.

192-193. -193. (canceled)

194. A method for detecting the presence of one or more analytes of interest optionally present in a sample comprising:

(a) forming a composition comprising

(i) said sample;

(ii) an assay-performance-substance comprising a label and at least one component chosen from;

(1) an added analyte of interest or an added analog of said analyte,

(2) a binding partner of said analyte or said analog, and

(3) a reactive component capable of binding with any analyte or analog of (1) or (2);

(iii) a plurality of magnetizable capture beads capable of specifically binding with at least one of the analyte or said assay-performance-substance;

(b) incubating said composition, wherein, in the presence of the analyte or analog of interest, linking between the magnetizable capture beads and the assay- performance-substance occurs;

(c) bringing said composition in fluidic contact with a liquid reagent distinct from the composition;

(d) applying a magnetic field across the composition and liquid reagent of step (c), wherein the magnetizable capture beads are moved into a measurement zone; and

(e) detecting the label in the measurement zone, wherein the presence, or lack of presence, of one or more analytes of interest is detected in the sample.

198. The method of claim 194, wherein the detecting step further comprises quantifying the presence of one or more analytes.

195-197. -197. (canceled)