Seconds-resolved pharmacokinetic measurements of the chemotherapeutic irinotecan in situ in the living body

Abstract

The ability to measure drugs in the body rapidly and in real time would advance both our understanding of pharmacokinetics and our ability to optimally dose and deliver pharmacological therapies.

High frequency, calibration-free molecular measurements in situ in the living body

“…In order to ease the adaptation of biosensors to clinical practice we present here a means of achieving calibration-free operation for electrochemical aptamer-based (E-AB) sensors, a broad class of in vivo biosensors that, because they are independent of the chemical or enzymatic reactivity of their targets, are quite versatile. [7][8][9][10][11][12][13][14] E-AB sensors are comprised of a redoxreporter-modied, target-recognizing oligonucleotide "probe" that is deposited on an interrogating electrode via the formation of a self-assembled monolayer. Due to binding-induced changes in probe conformation, in the environment of the redox reporter, or in probe exibility (e.g., due to the steric bulk of the target) the presence of target alters the kinetics with which electrons exchange to/from the redox reporter, producing an easily measurable change in current when the sensor is interrogated, for example, using square wave voltammetry.…”

Modified DNA Aptamers for C-Reactive Protein and Lactate Dehydrogenase-5 with Sub-Nanomolar Affinities

“…Thus, we spiked the saliva samples with recombinant analytes as a validation of binding, and showed specific bindings of the aptamers. Application of electrochemical sensing [47], acoustic sensing [48], or thermal sensing [49] may lead to highly sensitive target detection in such testing, as point-of-care testing [50,51].…”

An Electrochemical Biosensor Architecture Based on Protein Folding Supports Direct Real‐Time Measurements in Whole Blood

“…Target binding alters the probability with which the reporter approaches the electrode, thus inducing a change in electron transfer rate that is easily measurable when the sensor is interrogated electrochemically. The resulting seconds‐resolved molecular measurements can be performed in complex clinical samples and even in situ in the living body, providing a convenient, highly‐time‐resolved window into physiological status or treatment state. Indeed, using their real‐time output it has even proven possible to perform closed loop feedback control over drug delivery, providing unprecedented precision in the maintenance of plasma drug levels in the middle of the therapeutic window …”