Point-of-Care Technologies for the Advancement of Precision Medicine in Heart, Lung, Blood, and Sleep Disorders

Abstract

The commercialization of new point of care technologies holds great potential in facilitating and advancing precision medicine in heart, lung, blood, and sleep (HLBS) disorders. The delivery of individually tailored health care to a patient depends on how well that patient's health condition can be interrogated and monitored. Point of care technologies may enable access to rapid and cost-effective interrogation of a patient's health condition in near real time. Currently, physiological data are largely limited to single-time-point collection at the hospital or clinic, whereas critical information on some conditions must be collected in the home, when symptoms occur, or at regular intervals over time. A variety of HLBS disorders are highly dependent on transient variables, such as patient activity level, environment, time of day, and so on. Consequently, the National Heart Lung and Blood Institute sponsored a request for applications to support the development and commercialization of novel point-of-care technologies through small businesses (RFA-HL-14-011 and RFA-HL-14-017). Three of the supported research projects are described to highlight particular point-of-care needs for HLBS disorders and the breadth of emerging technologies. While significant obstacles remain to the commercialization of such technologies, these advancements will be required to achieve precision medicine.

Keywords: Biosensor; commercialization; point-of-care technologies; precision medicine.

FIGURE 1.

Benchmarking SELFA with relevant POC and lab-based assays. POC assays include lateral flow assay (LFA) and handheld enzyme-linked immunosorbent assay (ELISA). Lab-based assays include standard ELISA, ultra-sensitive ELISA (ELISA+), and high-definition immunoassay (HD-IMA). Solid and dashed outlines represent current and emerging assays, respectively. The detectable concentration ranges measured by the vertical axis are based on reported values. The cost, turnaround time, complexity, etc. gauged by the horizontal axis are based on the authors’ subjective estimation.

FIGURE 2.

SELFA POC product prototyping. The SELFA disposable cartridge prototype with integrated microfluidics for specimen preparation and assay operation (left). The foundry fabricated SELFA semiconductor chips with integrated amplifying nanowire transistor biosensor arrays (right).

FIGURE 3.

Serial blood sampling time lines for suspected AMI. Currently, the first blood biomarker test (T1) for the non-STEMI is mostly done in the ER setting (top row). With SELFA, the first test result can be obtained and transmitted out along with ECG data at the patient’s location (bottom row). This should clearly facilitate EMS triage and transport, increase ER throughput, permit alternative treatment earlier, and most importantly reduce patient restlessness.

FIGURE 4.

Total clearance (liters per hour) of doxorubicin in human subjects, as a function of body surface area (BSA). Note poor correlation, .07 (adapted from [29]).

FIGURE 5.

The conformational change between the bound and unbound aptamer (left) modulates the distance of the methylene blue redox center from the electrode surface, resulting in a concentration-dependent current through the electrode.

FIGURE 6.

Aptamer biosensor response measured in an experimental model of circulating whole blood from a “Smart IV™” platform during 8 hours in whole blood before and after the addition of doxorubicin.

FIGURE 7.

(a) An optical image of the microfluidic device for liquefaction of human sputum samples. (b) Photograph of human sputum samples: an un-liquefied raw sputum sample (R), a liquefied sputum sample by Vortex mixer (V), and a liquefied sputum sample by the microfluidic mixer (M). Diff-Quik staining results of cell samples obtained from (c) on-chip liquefied sputum sample and (d) Vortex mixer-liquefied sputum sample.