TSH antibodies for point-of-care immunoassay formats

• US 9,199,234 B2
• Filed: 11/29/2011
• Issued: 12/01/2015
• Est. Priority Date: 05/27/2011
• Status: Expired due to Fees

• Current Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories)
• Inventors: Wang, Dan, Collier, Gordon Bruce, Skinner, Joseph P., Ruan, Qiaoqiao, Tetin, Sergey Y.
• Primary Examiner(s): Gabel, Gail R
• Assistant Examiner(s): GRUN, JAMES LESLIE
• Application Number:
  US13/306,514
• Publication Number:
  US 20120301896A1
• Time in Patent Office: 1,463 Days
• Field of Search: 422/401, 422/403, 422/408, 422/412, 422/414, 422/417, 422/425, 422/82.01, 435/7.94, 435/285.2, 435/287.2, 435/287.9, 435/288.3, 435/288.4, 435/288.5, 436/501, 436/514, 436/518, 436/524, 436/525, 436/528, 436/534, 436/548, 530/388.24, 530/389.2, 530/391.1, 530/391.3
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/141 Preventing contamination, tampering
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2300/163 Biocompatibility
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• 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: C07K 16/26 against hormones ; against hormone releasing or inhibiting factors
• CPC Class Codes: G01N 2333/59 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: G01N 33/5302 Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/543 : with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: G01N 33/74 : involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
• CPC Class Codes: G01N 33/76 : Human chorionic gonadotropin including luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone or their receptors

Abstract

The invention relates to antibody characteristics used to design a whole blood Point of Care Thyroid Stimulating Hormone (TSH) immunoassay using an ELISA sandwich assay lacking one or more wash steps between the antigen capture, detection antibody addition and substrate introduction steps. This invention exhibits low cross reactivity with biologically similar interfering cross reacting species, such as Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Chorionic Gonadotropin (CG).

Claims

1. A device for performing an immunoassay for thyroid stimulating hormone (TSH) in a fluid sample, the device comprising an immunosensor in a conduit, said immunosensor having a capture antibody specific for TSH immobilized thereon, and said conduit having a dry reagent coating disposed therein, the dry reagent coating comprising a signal antibody configured to dissolve into said fluid sample;

wherein the capture antibody has a first dissociation constant (Kd) ratio, Kd (follicle stimulating hormone (FSH));

Kd(TSH), that ranges from 1500 to 10000, and the signal antibody has a second Kd ratio, Kd(FSH);

Kd(TSH), that ranges from 1500 to 3750;

wherein the first Kd ratio is greater than the second Kd ratio;

wherein the capture antibody and the signal antibody are epitope-compatible antibodies;

wherein the capture antibody and the signal antibody, respectively, are capable of binding to at least two different epitopes on a TSH-β

subunit of TSH;

wherein the capture antibody and the signal antibody each have a Kd for TSH of between 0.08 and 0.1 nM; and

wherein the capture antibody is mouse monoclonal anti-TSH-β

antibody 5409 and the signal antibody is mouse monoclonal anti-TSH-β

antibody M94206.

2. The device of claim 1, further comprising a metering chamber for metering the fluid sample, the metering chamber having a metering volume of from 1 to 500 μ

L.

3. The device of claim 2, further comprising a wash fluid pouch in fluid communication with the immunosensor, the pouch comprising from 5 to 500 μ

L of wash fluid.

4. A device for performing an immunoassay for thyroid stimulating hormone (TSH) in a fluid sample, the device comprising an immunosensor in a conduit, said immunosensor having a capture antibody specific for TSH immobilized thereon, and said conduit having a dry reagent coating disposed therein, the dry reagent coating comprising a signal antibody configured to dissolve into said fluid sample;

wherein the capture antibody has a first dissociation constant (Kd) ratio, Kd (follicle stimulating hormone (FSH));

Kd(TSH), that ranges from 1500 to 10000, and the signal antibody has a second Kd ratio, Kd(FSH);

Kd(TSH), that ranges from 1500 to 3750;

wherein the first Kd ratio is greater than the second Kd ratio;

wherein the capture antibody and the signal antibody are epitope-compatible antibodies;

wherein the capture antibody and the signal antibody, respectively, are capable of binding to at least two different epitopes on a TSH-β

subunit of TSH;

wherein the capture antibody and the signal antibody each have a Kd for TSH of between 0.04 and 0.1 nM; and

wherein the capture antibody is mouse monoclonal anti-TSH-β

antibody 5409 and the signal antibody is mouse monoclonal anti-TSH-β

antibody Ab9390.