Engineering innovations for small molecule and protein point-of-care tests towards home-health applications

Abstract

Laboratory tests play a vital role in the detection and management of diseases throughout the global healthcare system. Each year, billions of lab tests are used to help health care providers deliver effective and timely patient care. Currently, most testing is completed in centralized labs that provide highly accurate results but require expensive instrumentation and tests that can only be completed by trained professionals. While effective, logistical constraints within these centralized facilities often cause delays that negatively impact patient care and provider efficiency. For select tests this reliance on a centralized testing paradigm is insufficient. Examples of these tests include test that need to be run as urgently as possible, often without much notice (e.g., imaging following an acute injury) and frequent tests that need to be run repeatedly (e.g., blood glucose tests). Point-of-care-tests (POCTs) enable the transition of lab tests from centralized paradigms to a decentralized one. The strongest evidence of this is the point-of-care glucose test that has become ubiquitous in the management of diabetes for in-patient and remote health settings. POCTs lead to more available tests, improved patient outcomes, and reduced healthcare costs, but new technologies are required to enable POCTs for emerging clinical needs. One example is therapeutic drug monitoring (TDM). TDM is the practice of regularly (sometimes daily) testing patient blood samples to measure the amount of circulating drug concentrations to inform routine drug dosing adjustments and ensure efficacious treatments. TDM is essential for more than 250 narrow therapeutic index drugs, like vancomycin and tacrolimus, due to highly variable inter- and interpatient pharmacokinetics and pharmacodynamics. Beyond TDM, novel prognostic POCTs are desired to improve the clinical care of complex diseases, like neural injuries in veterinary medicine and multi-organ transplants. This dissertation provides a comprehensive review of technologies used for POCT (Chapter 2), and prototype POCTs designed for canine neural injury prognosis (Chapter 3), vancomycin (Chapter 4) and tacrolimus TDM (Chapter 5), and improved management of vascular composite allotransplantations (Chapter 6). The studies described herein, highlight the potential of prototype POCTs to enable success for emerging objectives at the clinical bedside, in outpatient health facilities, and in future in-home health settings.