Towards a personalized approach to aromatase inhibitor therapy: a digital microfluidic platform for rapid analysis of estradiol in core-needle-biopsies.

Despite advances in breast cancer prevention and treatment, variability in patient-response has revealed the need for a more "personalized" approach to medicine, in which treatments are tailored to each patient's biology. Motivated by this idea, we introduce a technique that allows for quantification of small-molecule analytes directly from core needle biopsy (CNB) tissue samples on a miniaturized platform. The new technique, powered by digital microfluidics, integrates tissue-liquid extraction and magnetic bead-based competitive immunoassay for quantification of estradiol in milligram-sized CNB samples. Each measurement (from start to finish) requires ∼40 minutes, a duration consistent with a visit to a doctor's office. The performance of the new technique was validated by the gold-standard analysis method (high performance liquid chromatography coupled to tandem mass spectrometry), and was applied to evaluate human patient samples before and after a course of treatment with aromatase inhibitor therapy. We propose that the new technique has great potential for eventual use for fast, automated, and quantitative analysis of biomarkers in tissue samples, towards a personalized medicine approach.

A microfluidic technique for quantification of steroids in core needle biopsies.

Core needle biopsy (CNB) sampling is known to be inexpensive and minimally invasive relative to traditional tissue resectioning. But CNBs are often not used in analytical settings because of the tiny amount of sample and analyte. To address this challenge, we introduce an analytical method capable of multiplexed steroid quantification in CNB samples-those studied here ranged in mass from 2 to 8 mg. The new method uses digital microfluidics to extract steroids from CNB tissue samples (including a solid-phase extraction cleanup step) followed by analysis by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The method has limits of detection of 3.6, 1.6, 5.8, and 8.5 fmol for estradiol, androstendione, testoterone, and progesterone, respectively. We propose that future generations of this method may be useful for regular quantification of steroids in core needle biopsy samples of breast tissue to inform dosage and timing of antihormone or hormone replacement therapies as part of a personalized medicine approach to treating a variety of hormone-sensitive disorders.