Method and apparatus for detecting estradiol and metabolites thereof using an acoustic device

• US 20070042441A1
• Filed: 05/02/2006
• Published: 02/22/2007
• Est. Priority Date: 05/02/2005
• Status: Active Grant

• Current Assignee: ProterixBio, Inc.
• Original Assignee: BioScale, Inc.
• Inventors: Srivastava, Alok, Miller, Michael, Lundstrom, Mark, Masters, Brett, Wang, Wayne, Gulati, Vishal
• Granted Patent: US 7,615,381 B2
• Time in Patent Office: Days
• US Class Current: 435/7.500
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/02836 Flow rate, liquid level
• CPC Class Codes: G01N 2291/0422 Shear waves, transverse waves, horizontally polarised waves
• CPC Class Codes: G01N 2291/0423 Surface waves, e.g. Rayleigh waves, Love waves
• CPC Class Codes: G01N 2291/0426 Bulk waves, e.g. quartz crystal microbalance, torsional waves
• CPC Class Codes: G01N 2291/0427 Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever
• CPC Class Codes: G01N 2800/324 Coronary artery diseases, e.g. angina pectoris, myocardial infarction
• CPC Class Codes: G01N 29/022 Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices microdevices per se B81B
• CPC Class Codes: G01N 29/036 by measuring frequency or resonance of acoustic waves
• CPC Class Codes: G01N 29/4418 with a model, e.g. best-fit, regression analysis
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/56911 Bacteria
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods for detecting estradiol and metabolites thereof in a sample are provided. A plurality of particles, each of which is coated with a capture agent having an affinity for estradiol, is combined with the sample to form a plurality of estradiol-particle complexes. The system also includes a transport arrangement for transporting the sample and/or particles to the sensor surface, and optionally a magnetic field inducing structure constructed and arranged to establish a magnetic field at and adjacent to the sensor surface. The resonant sensor produces a signal corresponding to an amount of estradiol-particle complexes that are bound to the sensor surface.

Claims

1. A method for detecting estradiol in a sample, the method comprising the steps of:

a) introducing a plurality of particles coated with a capture agent capable of binding estradiol into a fluid chamber, wherein at least one surface of the fluid chamber comprises an acoustic device having estradiol bound thereto, and

b) monitoring signal output by said acoustic device, thereby detecting estradiol in the sample.

2. The method of claim 1, wherein the acoustic device is a flexural plate wave device.

3. The method of claim 1, wherein an increased level of estradiol compared to a reference is indicative of the individual having an increased likelihood of developing breast cancer.

4. The method of claim 1, wherein prior to being introduced into the fluid chamber, said plurality of particles has been exposed to the sample.

5. The method of claim 1, wherein the sample has been introduced into the fluid chamber prior to introducing the plurality of particles.

6. The method of claim 1, wherein the particles are magnetic and further comprising creating a magnetic flux in proximity to the acoustic device to attract at least one of the plurality of magnetic particles toward the at least one surface.

7. The method of claim 6, wherein the magnetic flux is removed prior to step b).

8. The method of claim 1, wherein the estradiol is present in the sample at a concentration of about 10 pg/ml.

9. The method of claim 1, wherein the estradiol is selected from the group consisting of free estradiol, sex hormone-binding globulin (SHBG)-bound estradiol, estrone-3-glucuronide, and estradiol-3-glucuronide.

10. The method of claim 1, wherein the sample is selected from the group consisting of blood, serum, plasma, urine, saliva, and biopsy material.

11. The method of claim 1, further comprising comparing the signal output of b) to a control signal.

12. The method of claim 11, wherein the control signal is a standard curve.

13. The method of claim 11, wherein the control signal is obtained in the absence of sample.

14. The method of claim 1, wherein the estradiol is indirectly bound to said surface.

15. The method of claim 14, wherein said surface is coated with a first member of a binding pair, and the estradiol is bound to a second member of the binding pair.

16. The method of claim 15, wherein the binding pair is selected from the group consisting of biotin/avidin, biotin/streptavidin, and biotin/neutravidin.

17. The method of claim 1, wherein the capture agent is an antibody.

18. A method for detecting estradiol in a sample, the method comprising the steps of:

a) introducing a plurality of particles and a competitor molecule into a fluid chamber, said particles being coated with a first capture agent capable of binding estradiol, wherein at least one surface of the fluid chamber comprises an acoustic device that has been coated with a second capture agent capable of binding to the competitor molecule, and

b) monitoring signal output by said acoustic device, thereby detecting estradiol.

19. The method of claim 18, wherein the acoustic device is a flexural plate wave device.

20. The method of claim 18, an increased level of estradiol compared to a reference is indicative of the individual having an increased likelihood of developing breast cancer.

21. The method of claim 18, wherein prior to being introduced into the fluid chamber, said plurality of particles has been exposed to the sample and to the competitor molecule.

22. The method of claim 21, wherein the competitor molecule comprises estradiol bound to a tag and the second capture agent is capable of binding to the tag.

23. The method of claim 22, wherein the tag is biotin.

24. The method of claim 19, wherein the competitor molecule comprises two or more estradiol molecules bound to a carrier, and the second capture agent is capable of binding estradiol.

25. The method of claim 24, wherein the carrier is a selected from the group consisting of horseradish peroxidase and albumin.

26. The method of claim 18, wherein the particles are magnetic and further comprising creating a magnetic flux in proximity to the acoustic device to attract at least one of the plurality of magnetic particles toward the at least one surface.

27. The method of claim 26, wherein the magnetic flux is removed prior to step b).

28. The method of claim 18, wherein the estradiol is present in the sample at a concentration of about 10 pg/ml.

29. The method of claim 18, wherein the estradiol is selected from the group consisting of free estradiol, sex hormone-binding globulin (SHBG)-bound estradiol, estrone-3-glucuronide, and estradiol-3-glucuronide.

30. The method of claim 18, wherein the sample is selected from the group consisting of blood, serum, plasma, urine, saliva, and biopsy material.

31. The method of claim 18, further comprising comparing the signal output of b) to a control signal.

32. The method of claim 31, wherein the control signal is generated in the absence of sample.

33. The method of claim 31, wherein the control signal is a standard curve.

34. The method of claim 18, wherein the capture agent is indirectly bound to the at least one surface of the fluid chamber.

35. The method of claim 34, wherein the at least one surface is coated with a first member of a binding pair, and the capture agent is bound to a second member of the binding pair.

36. The method of claim 35, wherein the binding pair is selected from the group consisting of biotin/avidin, biotin/streptavidin, and biotin/neutravidin.