Engineering Innovations for Fundamental Biology and Translational Medicine

Abstract

The growing understanding of genomics and the increasing amount of clinical evidence has revealed that prescribing treatments based on population average is no longer an effective healthcare strategy because treatments that help some patients can be ineffective or harmful for others. This necessitates the transformation of healthcare toward the personalized medicine approach, in which clinicians perform accurate diagnostic tests to determine treatment and prevention plans that will work best for each individual. As the effectiveness of personalized medicine relies on the accuracy of the diagnostic and prognostic tests performed on the patient-derived specimen, the field is inevitability technology driven. In this special issue of SLAS Technology, we showcase reviews and original research reports addressing this technology demand for personalized medicine. The collection begins with two review articles assessing the role of microfluidic technology in patient-specific information collection. The review by Chowdury et al. emphasize the importance of ex vivo hematologic tumor models, which are patient specific and physiologically relevant, and their applications in targeted drug discovery and clinical diagnostics. The review provides an overview of state-of-the-art cell-based microfluidic platforms, enabling greater spatial and temporal control over stimuli and microenvironmental factors. Such control to obtain quantitative, personalized information is essential for safety and efficacy assessments in the early phase of clinical trials, hence reducing the failure of newly developed drug compounds. In addition to recapitulating patient-specific features of the disease, exquisitely sensitive and specific biomarkers can serve a critical role to identify cohorts expected to derive benefit or harm from the treatment and to monitor the disease progression and therapeutic efficacy. Among various biomarkers, extracellular vesicles found in bodily fluids have emerged as a new set of candidates to obtain the patient’s own molecular data that guide diagnosis and treatment in a minimally invasive manner. Zhang et al. provide a comprehensive review on the advancement in technology development and its limitations for effective isolation of nanoscale, nearly neutrally buoyant, heterogeneous vesicles. The review shares technological challenges that need to be overcome for unbiased and consistent results to advance the understanding of extracellular vesicles’ biological activities and their therapeutic potential. The remainder of this special issue includes original research articles that illustrate endeavors to integrate innovative technologies with existing clinical workflows through automation and miniaturization for expedited translation. The automation and user-friendliness of the systems not only enhance technology adoption by clinicians and clinical laboratory technicians but also improve standardization and commercial scalability. Reardon et al. report an automated workflow of activity-based protein profiling that is integrated with clinical laboratory technology for accurate and fast measurements of drug–target interaction in vivo. By utilizing commercially available resources and software, they integrated microfluidic devices and optimized the workflow to dramatically shorten operating time and reduce sample volumes with compatible detection sensitivity to conventional counterparts. In vivo drug-inhibited enzymatic activity measured from harvested tissue and the signal enhancement were strong enough to detect endogenous protein activity. In the article by Fox et al., automated multilayered artificial skin fabrication was demonstrated by the injection molding process. The small footprint of the system utilizing single-use, sterilizable, and customizable plastic molds allowed for the cost-effective fabrication of viable dermal and epidermal layers with preserved geometry accuracy and skin-equivalent morphology. When combined with robotic manipulation, it is anticipated that this technology will be scaled for clinically applicable skin graft fabrication. Accurate point-of-care tests performed at the clinical care sites or by the patient will provide fast turnaround of test results on patient specimens with the potential for timely treatment decisions toward patient-centered healthcare. 875449 JLAXXX10.1177/2472630319875449SLAS TECHNOLOGY: Translating Life Sciences InnovationHur and Kim research-article2019