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.
Highlights
Personalized medicine requires healthcare customization with medical practices, treatments, decisions, or products specific for each patient
We demonstrate that similar nanojunctions can be created in PMMA using controlled dielectric breakdown and that a device with two different sized nanojunctions can be used for the analysis of aminoglycoside antibiotic drugs in whole blood
5(6)-Carboxy-X-rhodamine (ROX), R-phycoerythrin (RPE), fluorescein, fluorescamine, bovine serum albumin (BSA), Ferric chloride (FeCl3 ), aminoglycoside antibiotics, hexadimethrine bromide (HDMB), hydroxypropyl methylcellulose (HPMC), sodium tetraborate, di-sodium hydrogen phosphate, and sodium phosphate monobasic for buffer preparation were purchased from Sigma-Aldrich (Sydney, Australia)
Summary
Personalized medicine requires healthcare customization with medical practices, treatments, decisions, or products specific for each patient. For targets where there is insufficient specificity in these approaches, they are usually analysed with a high resolution separation, which is much harder to miniaturise than an immunoassay This capability has been recently demonstrated through the introduction of a portable electrophoretic device, Medimate [9], which can measure lithium levels in blood. The potential of the device for TDM was demonstrated with the determination of the antibiotic ampicillin from whole blood within 5 min This device was fabricated in Polydimethylsiloxane (PDMS) where large-volume production is not possible through hot embossing or injection molding. We demonstrate that similar nanojunctions can be created in PMMA using controlled dielectric breakdown and that a device with two different sized nanojunctions can be used for the analysis of aminoglycoside antibiotic drugs in whole blood
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