Method and apparatus for therapeutic drug monitoring using an acoustic device
Methods for therapeutic drug monitoring are provided. A plurality of particles, each of which is coated with a capture agent capable of binding a therapeutic drug of choice is combined with the sample to form a plurality of therapeutic drug-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 therapeutic drug-particle complexes that are bound to the sensor surface.
1. A method for detecting one or more immunosuppressants in a sample, the method comprising the steps of:
a) introducing a fluid comprising a sample, a plurality of magnetic particles and a competitor molecule into a fluid chamber, said magnetic particles being coated with a first capture agent capable of binding an immunosuppressant, wherein at least one surface of the fluid chamber comprises a flexural plate wave device that has been coated with a second capture agent capable of binding to the competitor molecule, 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 to attract the magnetic particles in the fluid toward the membrane;
c) monitoring a first signal output by the 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 the immunosuppressant.
2. The method of claim 1 , further comprising adjusting dosage of said immunosuppressant administered to an individual based on the level of said drug in the sample.
3. The method of claim 1 , wherein prior to being introduced into the fluid chamber, said plurality of magnetic particles has been exposed to the sample and to the competitor molecule.
4. The method of claim 1 , wherein the competitor molecule comprises the immunosuppressant bound to a tag and the second capture agent is capable of binding to the tag.
5. The method of claim 4 , wherein the tag is biotin.
6. The method of claim 1 , wherein the competitor molecule comprises two or more immunosuppressant molecules bound to a carrier, and the second capture agent is capable of binding the immunosuppressant.
7. The method of claim 6 , wherein the carrier is a selected from the group consisting of horseradish peroxidase and albumin.
8. The method of claim 1 , wherein the sample is selected from the group consisting of blood, serum, plasma, cerebrospinal fluid, urine, saliva, and biopsy material.
9. The method of claim 1 , wherein the immunosuppressant is selected from the group consisting of cyclosporine, tacrolimus, rapamycin, and mycophenolate mofetil.
10. The method of claim 1 , wherein the control signal is obtained without the sample.
11. The method of claim 1 , wherein the control signal is a standard curve.
12. The method of claim 1 , wherein the second capture agent is indirectly bound to said surface.
13. The method of claim 12 , 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.
14. The method of claim 13 , wherein a first member of the binding pair is biotin.
15. The method of claim 1 , wherein the first or the second capture agent is an antibody.
16. The method of claim 13 , wherein a second member of the binding pair is a derivative of avidin.
17. The method of claim 1 , wherein a fluid flows across the membrane during one or more of steps of a), b), c) and e).