Point-of-care assay using Blood Glucose Meter for early warning of chronic lung rejection

Project SummaryAbstractLung transplantation is the last treatment option for patients with end stage lung diseases and to improve life expectancy and qualityWhile current technology has significantly improved the short term survival rateslongterm survival remains a challenge due to chronic lung rejectionattributed to the development of Bronchiolitis Obliterans SyndromeBOSan irreversible and progressive decrease in lung functionBesides lung transplantBOS is also a severe complication for patients receiving allogeneic hematopoietic cell transplantCurrentlydiagnosis of BOS relies on the substantial and progressive reduction of lung function as measured by spirometrybut such a diagnosis would be too late for most treatments in order to slow down the deterioration of lung functionRecentlyseveral biomarkersincluding endothelinETsCDand KLhave been identified as predictive markers for BOSmaking early warning possibleHowevercurrent methods for detecting these biomarkers are either cumbersome or expensive for point of carePOCsettingsTo overcome these technological barriers in order to achieve the goal of providing early warning for BOSwe propose to develop a user friendly device for POC monitoring for levels of ETsCDand KLbased on the existing blood glucose meterBGMtechnologyBy converting and amplifying the binding of non glucose targets to their antibodies to release an enzyme called invertasewhich catalyzes the conversion of sucrose to glucoseconcentrations of these markers can be correlated to glucosewhich can then be directly measured by a BGMSpecificallybased on the method developed for the ETassaywe will first demonstrate the chemistry to obtain the critical invertase sCDandKLconjugatesfollowed by assay developmentoptimizationsand last to integrate the optimized assays with an existing prototype cartridge systemUnlike current assays that rely on delicate instrument with highly trained operatorsour proposed system is simple and inexpensive to be used at the POC settingsIn additionthe biomarker tests will be utilize the same platform GlucoSentient has developed for tacrolimusan immunosuppressant widely used by transplant patients and requires close monitoringToday s BGM is the culmination of decades of research and developmentdesigned for convenient operationlow cost and large scale productionLeveraging the BGM technology allows us to reduce the risks and costs associated with device development and scale up productionBy combining the gold standard of antibody based assays with the low cost and easy to use BGM technologywe aim to develop a single product that allows posttransplant patients and their doctors to monitor the risk of developing BOS and immunosuppressant levelsThe proposed assays for BOS markersalongside a recently developed assay to monitor tacrolimusthe most common immunosuppressant for lung transplanthas great potential to benefit both the physicians and patients to prevent chronic lung rejection and to improve long term patient outcome Project NarrativeBuilding on existing low cost blood glucose meter hardwareGlucoSentient proposes to develop point ofcare tests for the quantification of endothelinsoluble CDand KLserum markers for early warning of Bronchiolitis Obliterans Syndromewhich is the major limiting factor for the long term survival of lung transplant patientsas well as hematopoietic cell transplant patientsEarly detection of BOS can lead to more effective therapies aimed at stabilizing the diseasewhich is important as the effects of BOS are currently irreversible by existing treatmentsProviding patients as well as physicians with a low costeasy to useand accurate prognostic tests for BOS can improve lung transplant patientslife expectancyquality of lifeand decrease healthcare costs