Biosensors
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The capability to continuously monitor specific biomolecules in vivo, as opposed to the current standard end-point assay, introduces a new dimension in medicine and healthcare to achieve more accurate disease diagnosis [1] and optimized treatment [2]. Unfortunately, only a handful of analytes, e.g., glucose and blood oxygen, can be currently measured in real-time. To overcome this limitation, our group and others have previously utilized aptamers, synthetic antibodies, to achieve real-time detection in vivo [3]. Aptamers are single-stranded DNA with specific sequences designed to achieve high binding affinity to the target analytes at high specificity for direct use in complex biological samples. Importantly, aptamers can be labeled with redox reporters and engineered to undergo structure-switching in which the binding of the target analyte gives rise to changes in the redox current when detected electrochemically. Thus, reagent is not needed and sub-minute temporal resolution is achievable. Nevertheless, the current generation of aptamer-based real-time biosensors require either a continuous drawing of the subject’s blood using microfluidics [2] or a wired connection [4], in which the system is only suitable for non-ambulatory patients.
To overcome this critical limitation, we present a miniaturized wireless implantable system [5] using ultrasound (US) powering and communication with an electrochemical “surface” sensor to interrogate with kanamycin (an aminoglycoside antibiotic) and doxorubicin (a chemo-therapeutic drug) aptamers for therapeutic drug monitoring (TDM) either directly in the bloodstream or in the perivascular extracellular matrix (ECM) near the tumor site (shown below, on the left). In the latter, the system will be implanted after cancer surgery to monitor drug concentration at the targeted location. The readout scheme for structure-switching aptamers is shown below, in the center; the implant system architecture is shown below, on the right.
Left: The applications of the proposed implant system. Center: The operation of structure-switching aptamers; binding of the target analytes leads to the modulation of MB electron transfer rate and can read out electrochemically using square-wave voltammetry (SWV). Right: Implant system architecture.
[1] H. Hall, PLoS Biol, 16(7), 2018.
[2] P. L. Mage, Nature BME, 1(0070), 2017.
[3] B. S. Ferguson, Sci. Trans. Med, 5(213), 2013.
[4] N. Arroyo-Currás, PNAS, 114(4), 2017.
[5] J.-C. Chien, et al., VLSI-C, 2019.