Integrated Microfluidic Devices Fabricated in Poly (Methyl Methacrylate) (PMMA) for On-site Therapeutic Drug Monitoring of Aminoglycosides in Whole Blood

Abstract

On-site therapeutic drug monitoring (TDM) is important for providing a quick and accurate dosing to patients in order to improve efficacy and minimize toxicity. Aminoglycosides such as amikacin, gentamicin, and tobramycin are important antibiotics that have been commonly used to treat infections of chronic bacterial infections in the urinary tract, lung, and heart. However, these aminoglycosides can lead to vestibular and auditory dysfunction. Therefore, TDM of aminoglycosides is important due to their ototoxicity and nephrotoxicity. Here, we have developed a hot embossed poly (methyl methacrylate) (PMMA) microfluidic device featuring an electrokinetic size and mobility trap (SMT) to purify, concentrate, and separate the aminoglycoside antibiotic drugs amikacin, gentamicin, and tobramycin. These drugs were separated successfully from whole blood within 3 min, with 30-fold lower detection limits compared to a standard pinched injection. The limit of detections (LOD) were 3.75 µg/mL for gentamicin, 8.53 µg/mL for amikacin, and 6.00 µg/mL for tobramycin. These are sufficient to cover the therapeutic range for treating sepsis of 6–10 μg/mL gentamicin and tobramycin and 12–20 μg/mL of amikacin. The device is simple and could be mass produced via embossing or injection molding approaches.