Claims for Patent: 10,126,296

Summary for Patent: 10,126,296

Title:	Immunoassay method and device with magnetically susceptible bead capture
Abstract:	The present invention provides apparatus and methods for the rapid determination of analytes in liquid samples by immunoassays incorporating magnetic capture of beads on a sensor capable of being used in the point-of-care diagnostic field.
Inventor(s):	Miller; Cary James (Ottawa, CA)
Assignee:	Abbott Point of Care Inc. (Princeton, NJ)
Application Number:	13/204,109
Patent Claims:	1. A magnetic immunosensing device for detecting an analyte in a sample, comprising: a sample entry port for receiving the sample, a sample entry chamber in fluid communication with the sample entry port; a dry reagent comprising magnetically susceptible beads coated with an antibody to the analyte in the sample, wherein the dry reagent is present in the device as a coating in the sample entry port or the sample entry chamber, and is dissolved into the sample upon receiving the sample in the sample entry port or the sample entry chamber; a first conduit comprising a first portion in fluid communication with the sample entry chamber; a substantially planar chip positioned in a second portion of the conduit in fluid communication with the first portion of the first conduit, the chip comprising: a sensing electrode positioned in the second portion of the first conduit to detect activity of an electroactive species caused by binding of the analyte to the antibody and generate a sensor response; and a conductivity sensor positioned in the second portion of the first conduit and adjacent to the sensing electrode to monitor a position of the sample within the second portion of the first conduit relative to the sensing electrode; a sample diaphragm in communication with the sample entry chamber via a second conduit, wherein the sample diaphragm is capable of forcing air through the second conduit causing the sample and the beads to move from the sample entry chamber into the second portion of the first conduit and over the chip; an analyzer comprising a motor driven plunger to move the sample through the conduit, wherein the analyzer is in contact with the sample diaphragm; and a magnet that is either a permanent magnet or an electromagnet having a magnetic field of greater than 0.1 Tesla, wherein the magnet is positioned proximate to the chip for attracting the beads in the second portion of the first conduit substantially proximate to the sensing electrode and substantially retaining the beads at the sensing electrode surface during removal of unbound sample and washing of the sensing electrode with a wash fluid. 2. The device of claim 1, wherein the magnet is the permanent magnet. 3. The device of claim 1, wherein the magnet is the electromagnet. 4. The device of claim 1, wherein the sensing electrode is microfabricated. 5. The device of claim 1, wherein the sample is selected from the group consisting of blood, plasma, serum, urine, interstitial fluid and cerebrospinal fluid. 6. The device of claim 1, wherein the sample is amended with an anticoagulant. 7. The device of claim 1, wherein the permanent magnet or the electromagnet is positioned in a non-coplanar position relative to said chip. 8. The device of claim 1, wherein the permanent magnet is selected from the group consisting of samarium cobalt (SmCo) alloy, aluminum nickel cobalt alloy (AlNiCo) and ferrite. 9. The device of claim 1, wherein the permanent magnet comprises neodymium iron boron (NdFeB) alloy. 10. The device of claim 1, wherein the permanent magnet comprises Nd.sub.2Fe.sub.14B. 11. The device of claim 1, wherein the permanent magnet or the electromagnet is a bulk magnet. 12. The device of claim 1, wherein the permanent magnet or the electromagnet is a substantially cylindrical bulk magnet. 13. The device of claim 1, wherein the permanent magnet or the electromagnet is a substantially cylindrical bulk magnet, having a diameter in the range of about 0.1 mm to about 5 mm and a length of about 0.1 mm to about 5 mm. 14. The device of claim 1, wherein the permanent magnet or the electromagnet is positioned to yield a bead event horizon in the conduit in the range of up to about 200 .mu.m from the region of the sensing electrode. 15. The device of claim 1, wherein the beads comprise ferrite. 16. The device of claim 1, wherein the beads comprise magnetite (Fe.sub.3O.sub.4). 17. The device of claim 1, wherein the beads comprise a magnetically susceptible core with a polymer coating. 18. The device of claim 1, wherein the beads have an average particle size of from 0.01 .mu.m to 20 .mu.m. 19. The device of claim 1, wherein the beads have an average particle size of from 0.1 .mu.m to 5 .mu.m. 20. The device of claim 1, wherein the beads have an average particle size of from 0.2 .mu.m to 1.5 .mu.m. 21. The device of claim 1, wherein the sensing electrode is amperometric. 22. The device of claim 1, wherein the sensing electrode is a gold microarray. 23. The device of claim 1, wherein the conduit has a height of about 0.2 mm to about 5 mm and a width of about 0.2 mm to about 5 mm. 24. The device of claim 1, wherein the conduit has a uniform cross-sectional area. 25. The device of claim 1, wherein the conduit has a non-uniform cross-sectional area. 26. The device of claim 1, wherein the analyte is selected from the group consisting of cardiac troponin I, troponin T, a troponin complex, human chorionic gonadotropin, BNP, creatine kinase, creatine kinase subunit M, creatine kinase subunit B, creatine kinase MB (CK-MB), proBNP, NT-proBNP, myoglobin, myosin light chain, galectin-3, and modified fragments thereof. 27. The device of claim 1, wherein the analyte is selected from the group consisting of beta-HCG, TSH, ultra hTSH II, TT3, TT4, FT3, FT4, myeloperoxidase, D-dimer, CRP, NGAL, PSA, LH, FSH, prolactin, progesterone, estradiol, DHEA-S, AFP, CA 125 II, CA 125, CA 15-3, CA 19-9, CA 19-9XR, CEA, thyroxine (T4), triiodothyronine (T3), T-uptake, Tg, anti-Tg, anti-TPO, ferritin, cortisol, insulin, HBsAg, HCV Ag/Ab combo, HCV core Ag, anti-HCV, AUSAB (anti-HBs), CORE, CORE-M, SHBG, iPTH, theophylline, sirolimus, tacrolimus, anti-HAV, anti-HAV IgM, HAVAB, HAVAB-M, HAVAB-M2.0, HAVAB-G, HAVAB 2.0, HAVAB 2.0 Quant, IgM, CMV IgM, CMV IgG, a-2-microglobulin, digitoxin, HBe, anti-HBe, HBeAg, HIV 1/2gO, HIV Ag/Ab combo, testosterone, SCC, vitamin B12, folate, syphilis, anti-HBc, rubella IgG, rubella IgM, homocysteine, MPO, cytomegalovirus (CMV) IgG Avidity, toxo IgG avidity, toxo IgG, toxo IgM, C-peptide, vitamin D, HTLV I/II, total ahCG, progesterone, estradrogen, prolactin, myoglobin, tPSA, fPSA, carbamazepine (CBZ), digoxin, gentamicin, NAPA, phenytoin, phenobarbital, valproic acid, vancomycin, procaine, quinidine, tobramycin, methamphetamine (METH), amphetamine (AMPH), barbituates, benzodiazepine, cannabis, cocaine, methadone, opiates, PCP, acetaminophen, ethanol, salicylates, tricyclics, holoTc, anti-CCP, HbA1c, barbs-U and modified fragments thereof. 28. A kit for performing an analyte immunoassay in a whole blood sample, comprising: a magnetic immunosensing device comprising: a sample entry port for receiving the sample, a sample entry chamber in fluid communication with the sample entry port; a dry reagent comprising magnetically susceptible beads coated with an antibody to the analyte in the sample, wherein the dry reagent is present in the device as a coating in the sample entry port or the sample entry chamber, and is dissolved into the sample upon receiving the sample in the sample entry port or the sample entry chamber; a first conduit comprising a first portion in fluid communication with the sample entry chamber; a substantially planar chip positioned in a second portion of the conduit in fluid communication with the first portion of the first conduct, the chip comprising: a sensing electrode positioned in the second portion of the conduit to detect activity of an electroactive species caused by binding of the analyte to the antibody and generate a sensor response; a conductivity sensor positioned in the second portion of the first conduit and adjacent to the sensing electrode to monitor a position of the sample within the second portion of the first conduit relative to the sensing electrode; a sample diaphragm in communication with the sample entry chamber via a second conduit, wherein the sample diaphragm is capable of forcing air through the second conduit causing the sample and the beads to move from the sample entry chamber into the second portion of the first conduit and over the chip; an analyzer comprising a motor driven plunger to move the sample through the conduit, wherein the analyzer is in contact with the sample diaphragm; a magnet that is either a permanent magnet or an electromagnet having a magnetic field of greater than 0.1 Tesla, wherein the magnet is positioned proximate to the chip for attracting the beads substantially proximate to the sensing electrode and substantially retaining the beads at the sensing electrode surface; and a reader for receiving the immunosensor cartridge and comprising: a motor driven plunger to apply pressure to the sample diaphragm and force the air through the second conduit causing the sample and the beads to move from the sample entry chamber into the second portion of the first conduit and over the chip; and an electrical contact to receive the sensor response from the sensing electrode, wherein the reader is capable of determining a concentration of the analyte from the sensor response. 29. The kit of claim 28, wherein the magnet is the permanent magnet. 30. The kit of claim 28, wherein the magnet is the electromagnet. 31. The kit of claim 28, wherein the immunoassay is a sandwich assay. 32. The kit of claim 28, wherein the immunoassay is a competitive assay. 33. The kit of claim 28, wherein over 50 wt. % of the beads are retained at the sensing electrode surface. 34. The kit of claim 28, wherein over 75 wt. % of the beads are retained at the sensing electrode surface.

Details for Patent 10,126,296

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	January 15, 1974	10,126,296	2031-08-05
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	December 27, 1984	10,126,296	2031-08-05
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 15, 1985	10,126,296	2031-08-05