Therapeutic Drug Monitoring (TDM) Point-of-Care Assays for LH, FSH, and hCG

Abstract

Gonadotrophins (FSH, LH, and human chorionic gonadotrophin) are used for women who have a problem with ovulation that either has not responded to clomifene, or that is not suitable for clomifene treatment. It may also be used for couples with unexplained infertility. To assist the therapeutic application of these gonadotrophins, rapid and quantitative point of care tests for these gonadotrophins are developed. Traditionally, these hormones are measured by ELISA assays that require blood to be drawn at either a doctor's office or a diagnostic laboratory. Rapid qualitative tests are available, but not suitable for TDM. Our point-of care (POC) assays combine lateral flow assays and coupled to an optical lateral flow reader with radio-frequency identification (RFID) capability. The reader utilizes confocal optics with a low distance-to-target ratio; and, the reflectometric measurement is converted to activity units, using an established calibration curve embedded in the RFID. The assays are quantitative, with dynamic ranges of 17-170 mIU/ml for LH, 0.01-10 IU/ml for FSH, and 3-300 mIU/ml for hCG. They exhibit linear correlation between nominal and actual values, with correlation coefficients greater than 0.95. They also comply with FDA guidance for bioanalytical assays. The POC tests utilize lateral flow cassettes that can read by the lateral flow reader, and the data can be printed out or stored on the reader for uploading onto the hospital database. The cassettes are made to be stable for up to 72 hours and can be read immediately or brought back to the central lab or doctor's office for quantitation. Rapid and quantitative POC tests for LH, FSH, and hCG have been developed for field deployment directly at home or in doctor's office. The cassettes can be read on-site or shipped to the central lab for reading. The availability of these tests should allow for TDM during the administration of these hormones for assisted reproduction. Not only would this approach save on cost by limiting doctor visits, but it is also patient-centric, inviting better compliance and patient participation in personalizing her treatment. Clinical trials are being conducted to obtain CLIA-waived status for these assays.