Highly Multiplexed Digital Assays

DESCRIPTION (provided by applicant): Pressure ulcers are a serious problem in clinical care. They are caused by immobility, moisture, and patient pathologies (Reddy 2006). They cause many poor outcomes including infection and amputation, and costs of 1B in the US and 3B- 5B worldwide (Salcido 2012, Russo 2006). Nursing processes use repositioning, skin checks, specialty support surfaces, and incontinence management. Risk scales such as those of Norton and Braden (NPUAP 1989, Bergstrom 1987) are currentlyused to identify patients at higher risk. While these processes and scales are valid, their ability to predict and manage ulcer occurrence are modest at best (Schoonhoven 2002) and pressure ulceration remains a significant healthcare cost and cause of pooroutcomes. Skin metabolites are known to contain volatiles produced by tissue metabolism and commensal bacteria of the skin (Gallagher 2008). Many of these are markers of oxidative stress (Pabst 2007, Aghdassi 2000, Dumelin 1977); therefore multiple markers are anticipated to be affected by the physiologic stresses which lead to pressure ulceration and to show unique spectral patterns for injury vs. those of intact skin. In order to ensure that ulceration-specific signals are sampled, in preference to systemic or environmental signals, it is important to sample and analyze markers obtained at high-risk skin sites. This will be done by use of polydimethylsilicone (PDMS) membrane methods (Thomas 2010) coupled with a proprietary ion-mobility sensor technologydeveloped by Applied Nanotech, Inc. (EZKnowz ). An inexpensive system will be developed for early detection of pressure ulceration by profiling of volatile markers with a portable, bedside analysis product. The near-real-time results of the analyses will be provided to the clinical team to guide the use of interventions. Specific Aim 1 is to develop and optimize VOC trapping methods with PDMS membranes. Specific Aim 2 is to develop an extraction interface and verify the biomarker analyses with the EZKnowztechnology. Specific Aim 3 is to test the feasibility of the approach in a pre- clinical model of pressure ulceration. An early-detection capability for pressure ulcers will allow for more appropriate use of interventions such as pressure relief and microclimate control surfaces or aggressive repositioning leading to better care for lower costs. One example of this is in distinguishing pre-emergent, community-acquired ulcers upon admission of a patient to a healthcare facility from those appear during in-house care. Correct classification will allow healthcare facility administrators to appropriately obtain reimbursement for treating them rather than have the ulcers classed as nosocomial ulcers, thereby losing out on reimbursement coverage. Patient outcomeswill be improved by reduced ulceration rates and more timely interventions. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The proposed project will combine and test existing technologies to help address the serious clinical problem of pressure ulcers, also known as bed sores . Pressure ulcers cost the US healthcare system 1B a year and cause many bad outcomes for patients including infections and amputations. By using advanced ion spectrometry, we will detect these ulcers before they have fully emerged and thereby direct more effective and timely interventions.