Despite extraordinary advances in proteomic technologies, we are still very far from realizing the full potential of protein biomarkers for clinical diagnostics. The FDA-approved list of clinically useful protein biomarkers numbers in the low 100s, and the rate of FDA approval has dwindled to less than one per year. And although putative new and more powerful "candidate" biomarkers to various diseases are frequently advanced, clinically validating them remains the biggest challenge facing modern clinical proteomics. Several factors play a role in this, not the least of which is pre-analytical sample acquisition. Biomarker validation requires collection and assessments of biofluids from a large and diverse population. Blood plasma is the biofluid of choice because it is most representative of the human proteome. The most common practice of blood sample collection is by venipuncture, performed by a registered phlebotomist using invasive hypodermic needles in clinical settings. Diurnal fluctuation and analytical variability necessitate multiple samples be drawn from the same individual over a period of time, vastly increase clinical validation study costs and complexity. Dried blood spot (DBS) technology is an emerging alternative. Blood collected by painful lancet-based finger stick can be store on DBS cards for analysis. However, despite patient training and instructions, a number of DBS samples do not meet minimum quality standards. Non-uniform blood distribution on the card often leads to erroneous or inconclusive results. A disk from the DBS has to be reconstituted in buffer, requiring optimization and introducing variability. Needle aversion also i a premier source of non-compliance. Very significantly, the measurement of low concentration analytes obtained from DBS cards is particularly error-prone due to the small sample size (low uL) and sample variability and to extant limitations of analytical sensitivity. This proposal discusses the development of a low-cost, single use device for minimally invasive and pain free self-collection of blood that can overcome limitations of DBS sampling and supplant costly, clinic-based blood sample collection. Our technology combines a pioneering, patented, and highly durable micro needle array with a revolutionary, miniature, low-cost, electrochemical micro vacuum that will allow controlled and reproducible, transdermal collection of intermediate volumes (0.1-0.5 mL) of capillary blood sufficient for most biomarker studies. Long term, our device will be designed to include an integrated blood cell filtration assembly for collecting plasma, which can be stored without degradation for prolonged periods, and it will be engineered to enable precisely controlled delivery of analytical plasma samples to in-line diagnostic devices.
The proposed technology will have very broad and significant impact on public health. The minimally invasive blood self-collection device will lower cost and complexity of population-based biomarker studies, and increase compliance, which would facilitate both biomarker discovery and validation and significantly advance clinical diagnostics. It can be used for large-scale human drug trial monitoring studies for expediting clinical testing and FDA approval of new drugs. Finally, the device will be an integral component of future point-of-care diagnostics, for discreet or continuous monitoring of disease, infection, environmental exposure, etc., helping realize the hitherto latent promise of 'personalized, pre-emptive, and preventive'medicine.