Biosensor‐Enabled Multiplexed On‐Site Therapeutic Drug Monitoring of Antibiotics

Abstract

Personalized antibiotherapy ensures that the antibiotic concentration remains in the optimal therapeutic window to maximize efficacy, minimize side effects, and avoid the emergence of drug resistance due to insufficient dosing. However, such individualized schemes need frequent sampling to tailor the blood antibiotic concentrations. To optimally integrate therapeutic drug monitoring (TDM) into the clinical workflow, antibiotic levels can either be measured in blood using point‐of‐care testing (POCT), or can rely on noninvasive sampling. Here, a versatile biosensor with an antibody‐free assay for on‐site TDM is presented. The platform is evaluated with an animal study, where antibiotic concentrations are quantified in different matrices including whole blood, plasma, urine, saliva, and exhaled breath condensate (EBC). The clearance and the temporal evaluation of antibiotic levels in EBC and plasma are demonstrated. Influence of matrix effects on measured drug concentrations is determined by comparing the plasma levels with those in noninvasive samples. The system's potential for blood‐based POCT is further illustrated by tracking ß‑lactam concentrations in untreated blood samples. Finally, multiplexing capabilities are explored successfully for multianalyte/sample analysis. By enabling a rapid, low‐cost, sample‐independent, and multiplexed on‐site TDM, this system can shift the paradigm of “one‑size‐fits‐all” strategy.

Multiplexed biosensor for point-of-care COVID-19 monitoring: CRISPR-powered unamplified RNA diagnostics and protein-based therapeutic drug management

“…In an attempt to provide a single platform that can perform both measurement of antibiotic concentration and detection of viral RNA in clinical samples, we combined two different assays on a 6-fold BiosensorX (Fig. 3a) : (i) a protein-based assay for ß-lactam monitoring 37 and (ii) a CRISPR/Cas13a powered assay for RNA sequences characteristic to an infection with COVID-19 (Fig. 3b) .…”

“…Functionalization of the immobilization area is accomplished by incubation with penicillin binding protein 3 (PBP-3 37 ; 250 µg ml −1 in PBS (10 mM; pH 7.4), expressed via in-house production) for 1 hour, followed by 30 minutes of blocking with biotin-free casein (85R-108, Fitzgerald, USA). The third step of the assay relies on the competitive binding of piperacillin-tazobactam and/or biotinylated ampicillin (0.2 µg ml −1 in PBS (10 mM; pH 7.4) obtained via in-house production) to PBP-3.…”

“…The success of the antibiotherapy, however, strongly depends on keeping the blood antibiotic concentrations within the "personalized" therapeutic range to minimize the risk of antibiotic resistance. Therefore, it is necessary to understand how the patient's body metabolizes the drug with respect to the individual pharmacokinetic (PK) response 36 , i.e., to monitor antibiotic level fluctuations in the serum of a patient 37 . Here we introduce BiosensorX, a novel, multiplexed single-channel biosensor, onto which we immobilize the CRISPR-powered assay as well as a protein-based antibiotic detection assay (Fig.…”

Artificial Intelligence: Its future in the health sector and its role for medical education

“…Implementing these technologies in the health sector would mean that every patient can be treated differently, thereby deviating from the established practice of clinical decision pathways. Clearly, such advanced methods are entering the health sector even without AI technology, for example as 3D printing of implants [ 18 ] or as innovative antibiotics sensor [ 19 ]. It is easily envisaged that this may be achieved also in the production of pharmaceuticals, where one may produce customised mixtures of well-established substances, tailored to the needs of an individual patient.…”

Authors’ Reply to De Sutter, De Waele, and Vermeulen: “Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update”

“…The use of exhaled breath condensate has already been used for non-invasive evaluation of lung diseases [ 15 ]. The combination of exhaled breath condensate samples with nanobiosensor sensitive analytical techniques and/or endogenous dilution markers (i.e., urea) should improve quantification issues of antibacterial concentrations [ 16 – 18 ]. However, further validation of these techniques will be needed and comparison to other sample collection methods of assessing intrapulmonary drug concentrations should be considered.…”