Assay Cartridges and Methods of Using the Same

• US 20090066339A1
• Filed: 10/02/2008
• Published: 03/12/2009
• Est. Priority Date: 12/26/2002
• Status: Active Grant

• Current Assignee: Meso Scale Technologies, LLC
• Original Assignee: Meso Scale Technologies, LLC
• Inventors: Jeffrey-Coker, Bandele, Glezer, Eli N., Debad, Jeff D., Billadeau, Mark A., Leginus, Joseph M., Phalnikar, Koustubh A., Leland, Jonathan K., Jambunathan, Sriram
• Granted Patent: US 8,012,745 B2
• Time in Patent Office: Days
• US Class Current: 324/444
• CPC Class Codes: A61M 25/0017 specially adapted for long-term hygiene care, e.g. urethral or indwelling catheters to prevent infections
• 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 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/0074 Biological products
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• 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 2300/0645 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 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• 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 3/5029 using swabs
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: G01N 21/76 : Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 2458/30 : Electrochemically active labels
• CPC Class Codes: G01N 27/30 : Electrodes, e.g. test electrodes; Half-cells G01N27/414 takes precedence
• CPC Class Codes: G01N 33/48707 : by electrical means G01N33/49, G01N33/493 take precedence
• CPC Class Codes: G01N 33/5438 : Electrodes
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 : including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

Assay modules, preferably assay cartridges, are described as are reader apparatuses which may be used to control aspects of module operation. The modules preferably comprise a detection chamber with integrated electrodes that may be used for carrying out electrode induced luminescence measurements. Methods are described for immobilizing assay reagents in a controlled fashion on these electrodes and other surfaces. Assay modules and cartridges are also described that have a detection chamber, preferably having integrated electrodes, and other fluidic components which may include sample chambers, waste chambers, conduits, vents, bubble traps, reagent chambers, dry reagent pill zones and the like. In certain preferred embodiments, these modules are adapted to receive and analyze a sample collected on an applicator stick.

Claims

1-224. -224. (canceled)

225. A method of performing a plurality of biochemical assays using a plurality of electrodes comprising the steps of:

(a) applying electrical energy between first and second electrodes of said plurality of electrodes;

(b) measuring an assay dependent signal at said second electrode;

(c) applying electrical energy between said second electrode and a third electrode of said plurality of electrodes; and

(d) measuring an assay dependent signal at said third electrode.

226. The method according to claim 225 wherein said assay dependent signal is selected from the group consisting of electrical current, electrical potential and electrode-induced luminescence.

227. The method according to claim 226 wherein said assay dependent signal is electrochemiluminescence.

228. The method according to claim 225, said second electrode having a second electrode assay reagent immobilized thereon and said third electrode having a third electrode assay reagent immobilized thereon.

229. The method according to claim 228 wherein said second electrode assay reagent and said third electrode assay reagent are binding reagents each specific for a different analyte of interest.

230. The method according to claim 225 wherein said plurality of electrodes are arranged within a flow cell, wherein said flow cell comprises a flow cell path.

231. The method according to claim 230 wherein said plurality of electrodes are arranged sequentially.

232. The method according to claim 225 wherein said first electrode is adjacent said second electrode and said second electrode is adjacent said third electrode.

233. The method according to claim 225 wherein said plurality of electrodes are arranged within a single detection chamber.

234. The method according to claim 225 wherein said plurality of electrodes comprise printed carbon ink.

235. The method according to claim 228 wherein said assay reagents are present within an assay domain defined by a dielectric layer on said electrodes.

236. The method according to claim 230 wherein:

said first, second and third electrodes having first, second and third electrical leads for supplying electrical energy to said electrodes; and

said flow cell being in fluid communication with an inlet conduit at least partially defined by exposed surfaces of said first and third electrical leads, wherein fluid in said inlet conduit is in electrical contact with said exposed surfaces,

wherein the method further comprises the step of applying an inlet conduit interrogation potential between said exposed surfaces to determine the presence or composition of fluid in said inlet conduit.

237. The method according to claim 236 wherein said interrogation potential is of insufficient magnitude to induce electrochemiluminescence at said first or third electrodes.

238. The method according to claim 225, further comprising the steps of:

applying electrical energy between said third electrode and a fourth electrode of said plurality of electrodes; and

measuring an assay dependent signal at said fourth electrode.

239. A method of performing a plurality of assays comprising measuring assay dependent signals using a plurality of electrodes, wherein at least one of said plurality of electrodes is used as a working electrode for measuring an assay dependent signal and, subsequently, as a counter electrode for measuring a different assay dependent signal at a different one of said plurality of electrodes.

240. The method of claim 239, wherein each of at least two of said plurality of electrodes is used as a working electrode for measuring an assay dependent signal and, subsequently, as a counter electrode for measuring a different assay dependent signal at a different one of said plurality of electrodes.

241. The method of claim 239, wherein said plurality of electrodes comprises a dedicated counter electrode, a dedicated working electrode and two or more additional electrodes, each of which is used as a working electrode for measuring an assay dependent signal and, subsequently, as a counter electrode for measuring a different assay dependent signal at a different one of said plurality of electrodes.

242. A method of conducting an electrochemiluminescence measurement, said method comprising the steps of:

measuring the impedance between two electrodes in a measurement chamber to detect the presence of air bubbles, said measurement using electrical potentials that are insufficient for generating electrochemiluminescence at said electrodes; and

inducing electrochemiluminescence at one of said two electrodes.

243. A method of forming a plurality of assay domains, the method comprising the steps of:

(a) treating one of a plurality of predefined region of a surface with solution of a second binding partner so as to form an adsorbed second binding partner layer within said predefined region of said surface;

(b) treating said adsorbed second binding partner layer with a solution comprising an assay reagent wherein said assay reagent is linked to or comprises a first binding partner and wherein said first and second binding partners specifically bind each other; and

(c) repeating steps (a) and (b) for each of said plurality of assay domains.

244. A method of performing a cartridge based assay, said cartridge comprising:

(a) a sample chamber having a sample chamber vent port, said sample chamber connected to a sample conduit comprising a first dry reagent, a first waste chamber connected through a first waste chamber conduit to said sample conduit, a first waste chamber vent port connected to said waste chamber;

(b) a first reagent chamber containing a volume of a first liquid reagent;

(c) a first reagent chamber vent port connected to said first reagent chamber;

(d) a first detection chamber connected to said sample chamber by said sample conduit and to said first reagent chamber by a first reagent chamber conduit;

(e) an air vent port connected to said sample conduit or said first reagent conduit;

said method comprising;

(i) moving said sample from said sample chamber into said first sample conduit;

(ii) reconstituting said first dry reagent in said sample;

(iii) moving a first slug of said sample having a predetermined volume into said first detection chamber;

(iv) moving said sample in said first detection chamber into said first waste chamber;

(v) moving said first liquid reagent into said first detection chamber; and

(vi) measuring a signal from said first detection chamber.