Rapid Microsensing-Based Active Point-of-Care Immunosuppression Tracking (MAP-IT) Biosensor Technology for Vascularized Composite Allotransplantation
Abstract
Vascularized composite allotransplantation (VCA) involves transplantation of multiple tissues including skin, bone, muscles, blood vessels, nerves, and connective tissue as a single functional unit (e.g., hand, or face). Over 200 VCA procedures have been performed worldwide over the past 15 years. Following VCA, patients are permanently dependent on immunosuppressive drugs (ISDs) for the rest of their lives to prevent immune rejection. Among the various ISDs, tacrolimus (TAC) has emerged as one of the most frequently used immunosuppressive drugs in VCA. For long-term survival of the graft, there is a need to achieve optimal therapeutic dosing of TAC, which is just strong enough to prevent rejection, but does not lead to over immunosuppression with increased risks of nephrotoxicity, cancer, and infection. Consistent and reliable maintenance of TAC drug levels in the blood within a therapeutic range that is not too high or too low is extremely challenging in patients after VCA. Currently, it requires frequent visits to medical facilities for blood collection (2-4 mL), a costly and time-consuming process of pre-analytical sample preparation and analysis (3-6 hours), and hence, delays the reporting of results to physicians for dose adjustments. This multistep-interface process puts an enormous burden on patients and impairs the quality of care and VCA outcomes. For example, Veterans and non-Veteran VCA patients often need to travel long distances to access a transplant facility, and reports show that patients located farther from a designated transplant center experienced worse outcomes. The situation is further exacerbated during pandemics. Additionally, patient non-compliance can cause wide fluctuations of drug levels, causing periodic or persistent under-immunosuppression conditions. Hence, the FY21 RTRP Focus Area addressed within the proposed work is to develop reliable non-invasive methods for monitoring VCA graft rejection via ISD detection by point-of-care (POC) devices at home/local physician/emergency/local pharmacy settings for rapid monitoring and is vital for delivering the right drug, at the right dose, and at the right time. The device should have rapid turnaround time of results swiftly sent to transplant centers for data analysis and dose adjustments via telehealth. Creating such POC benchtops or handheld devices (akin glucose sensor) will vastly improve clinical results, greatly lowering healthcare costs and obviating myriad unproductive time-intensive steps. The literature search to date reveals current non-availability of such ISD sensing devices. We aim to develop a simple yet highly selective and sensitive portable microsensing-based active point-of-care immunosuppression tracking (MAP-IT) testing platform for TAC utilizing only few drops of blood detecting TAC levels in less than 10 minutes. We will optimize MAP-IT biosensors to accurately measure systemic levels of TAC concentrations in the blood using electrochemical impedance spectroscopy. The proposed work includes miniaturization and development of a benchtop MAP-IT prototypes. These benchtop prototypes will consist of recyclable microelectrodes, small footprint analyzer, and user-friendly displays. The MAP-IT platform will be rigorously tested for sensitivity, selectivity, accuracy, and reproducibility using the blood/plasma of limb transplanted rat and kidney transplanted human patients at two separate locations. The main research aims proposed are: 1. Optimize the self-assembled monolayer of the MAP-IT biosensing platforms by assessing the ideal concentrations, incubation times, and combinations of specific functional layers, antigen concentrations, and single-frequency antigen detection. 2. Miniaturization of the biosensor electrodes, transducer, and display and development of a prototype benchtop device. 3. Assess MAP-IT performance against naive and limb-transplanted Lew rat whole blood and plasma to determin
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210987
Entities
People
- Fatih Zor
Organizations
- United States Army
- Wake Forest University