Method and apparatus for detecting estradiol and metabolites thereof using an acoustic device
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.
1. A method for detecting estradiol in a sample, the method comprising the steps of:
a) introducing a fluid comprising a sample and a plurality of magnetic particles coated with a first capture agent capable of binding estradiol into a fluid chamber, wherein at least one surface of the fluid chamber comprises a flexural plate wave device having a second capture agent capable of binding estradiol, wherein the flexural plate wave device has a membrane that is capable of vibrating, and wherein the second capture agent is bound to the membrane;
b) applying a retractable source of magnetic flux positioned external to the fluid chamber close to the membrane to create a significant magnetic field gradient at a surface of the membrane to attract magnetic particles in the fluid toward the membrane;
c) monitoring a first signal output by said flexural plate wave device, wherein the first signal output is monitored in the presence of a magnetic flux;
d) after removing the retractable source of magnetic flux, flowing a solution through the fluid chamber to remove magnetic particles not bound to the membrane;
e) monitoring a second signal output by said flexural plate wave device, wherein the second signal output is monitored in the absence of the magnetic flux; and
f) comparing the first and the second signal output to a control signal, thereby detecting estradiol in the sample.
2. The method of claim 1 , wherein an increased level of estradiol is detected compared to a reference, which indicates that an individual from whom the sample is obtained has an increased likelihood of developing breast cancer.
3. The method of claim 1 , wherein prior to being introduced into the fluid chamber, said plurality of particles has been exposed to the sample.
4. The method of claim 1 , wherein the sample has been introduced into the fluid chamber prior to introducing the plurality of particles.
5. The method of claim 1 , wherein a concentration of about 10 pg/ml is detected.
6. 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.
7. The method of claim 1 , wherein the sample is selected from the group consisting of blood, serum, plasma, urine, saliva, and biopsy material.
8. The method of claim 1 , wherein the control signal is a standard curve.
9. The method of claim 1 , wherein the control signal is obtained without the sample.
10. The method of claim 1 , wherein said second capture agent capable of binding the estradiol is indirectly bound to said surface.
11. The method of claim 10 , wherein said surface is coated with a first member of a binding pair, and the second capture agent is bound to a second member of the binding pair.
12. The method of claim 11 , wherein the first member of the binding pair is biotin.
13. The method of claim 1 , wherein the first or second capture agent is an antibody.
14. The method of claim 11 , wherein the second member of the binding pair is a derivative of avidin.
15. The method of claim 1 , wherein a fluid flows across the membrane during one or more of steps a), b), c) and e).