Analysis on the Go: Quantitation of Drugs of Abuse in Dried Urine with Digital Microfluidics and Miniature Mass Spectrometry

We report the development of a method coupling microfluidics and a miniature mass spectrometer, applied to quantitation of drugs of abuse in urine. A custom digital microfluidic system was designed to deliver droplets of solvent to dried urine samples and then transport extracted analytes to an array of nanoelectrospray emitters for analysis. Tandem mass spectrometry (MS/MS) detection was performed using a fully autonomous 25 kg instrument. Using the new method, cocaine, benzoylecgonine, and codeine can be quantified from four samples in less than 15 min from (dried) sample to analysis. The figures of merit for the new method suggest that it is suitable for on-site screening; for example, the limit of quantitation (LOQ) for cocaine is 40 ng/mL, which is compatible with the performance criteria for laboratory analyses established by the United Nations Office on Drugs and Crime. More importantly, the LOQ of the new method is superior to the 300 ng/mL cutoff values used by the only other portable analysis systems we are aware of (relying on immunoassays). This work serves as a proof-of-concept for integration of microfluidics with miniature mass spectrometry. The system is attractive for the quantitation of drugs of abuse from urine and, more generally, may be useful for a wide range of applications that would benefit from portable, quantitative, on-site analysis

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