SBIR-STTR Award

?The World Health Organization projects that the global diabetes cases will increase from 217 million in 2005 to 366 million by 2030 [1]. The rate of type-1 or autoimmune diabetes (T1D) in children is rising by 3% annually with a projected 70% increase between 2004 and 2020, while the rate of type-2 diabetes (T2D) has also been increasing exponentially in children partly due to the global obesity epidemic. Diagnosis of these diseases has become increasingly difficult. Currently, T1D diagnosis and screening tests for new, on-set patients are done by slow and costly radioimmunoassay (RIA), delaying definitive diagnosis and timely treatment. The RIA test may take up to two weeks to deliver a diagnosis, but clinical intervention is needed for T1D diagnosis in 24 hours or less in some cases. Due to the need for radioisotope generation and detection, the T1D test is inaccessible to developing countries and regions of the world with limited resources. Also, latent autoimmune diabetes adults (LADA) cases with positive autoantibodies are common, accounting for a non-trivial fraction of adult type-2 diabetes patients. Antibodies testing and screening for adult diabetes patients would also provide valuable information and guidance to LADA patient management and treatment. Of note, with T1D there is a markedly higher prevalence of Celiac Disease and Autoimmune Thyroid Disease (ATD), which are considered linked diseases. In US, autoimmune thyroid disease occurs in ~ 15 - 30% T1D patients and Celiac Disease occurs in 4 - 9% of T1d patients. We propose to develop and clinically test a multiplexed auto-immune antibody chip with simultaneous diagnosis of T1D, Celiac Disease, and ATD. The chip will provide a rapid, fluorescence-based diagnostic test using existing instrumentation found in the clinic, made possible by the unique signal-enhancing technology, pGOLD, available to Nirmidas Biotech. The pGOLD chip will detect autoantibodies in a patient's serum that indicate T1D, Celiac Disease, and ATD with the same performance as RIA in just 1-2 hours. This project will test the pGOLD chip with 150 patient serum samples as a pilot study as the initial step towards gaining regulatory approval and commercialization of the chip.

Public Health Relevance Statement:


Public Health Relevance:
The World Health Organization projects that the global diabetes cases will increase from 217 million in 2005 to 366 million by 2030, while accurately distinguishing Type 1 Diabetes from Type 2 Diabetes will become increasing difficult over that same time frame using epidemiologic assumptions. The gold standard test for differentiation of Type 1 and Type 2 Diabetes is radioimmunoassay, which takes up to two weeks and delays proper patient treatment. Nirmidas Biotech's patented fluorescence-amplifying technology will improve Type 1 Diabetes detection by making it more rapid and versatile. We will develop a multiplexed fluorescence assay based chip with the same effectiveness as radioimmunoassay but with a turn-around time of only a few hours and the additional capability to diagnose Celiac Disease and Autoimmune Thyroid Disease, which are commonly associated with Type 1 Diabetes.

NIH Spending Category:
Autoimmune Disease; Bioengineering; Diabetes; Nanotechnology; Pediatric; Prevention

Project Terms:
Accounting; Adult; Antibodies; Antigens; Autoantibodies; Autoimmune Diabetes; Autoimmune Diseases; Autoimmune Process; autoimmune thyroid disease; base; Biological Assay; Biological Markers; Celiac Disease; Child; Clinic; clinical Diagnosis; Clinical Research; Collaborations; commercialization; Data; Detection; Developing Countries; Development; Diabetes Mellitus; Diagnosis; Diagnostic tests; Disease; disease diagnosis; Early Diagnosis; Effectiveness; electric field; Enzyme-Linked Immunosorbent Assay; Epidemic; Epidemiology; Fluorescence; fluorophore; Foundations; Generations; Goals; Gold; Health; High Prevalence; Hour; Immune; Immune System Diseases; Immunoassay; Immunoglobulin G; improved; instrumentation; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention; islet; Legal patent; Link; Morbidity - disease rate; nano; nanocoating; nanostructured; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Patients; Performance; Phase; Pilot Projects; plasmonics; Population; prevent; Production; programs; Protocols documentation; prototype; public health relevance; Radioimmunoassay; Radioisotopes; rapid detection; Resources; Risk; Sampling; scale up; screening; Sensitivity and Specificity; Serum; Signal Transduction; Standardization; Surface Plasmon Resonance; Technology; Testing; Time; type I and type II diabetes; World Health Organization

The incidence of type 1 diabetes (T1D) is increasing rapidly around the world, with prevalence expected to rise by 150 % between 2010 and 2025. The rate of T1D increase is most notable in children 0 to 4 years of age, and in individuals previously considered at low- to moderate- genetic risk. This trend underscores an unmet need for T1D prevention strategies. Early identification of children at-risk for pancreatic islet cell injury is our best opportunity for T1D prevention. IgG autoantibodies targeting islet antigens (specifically insulin, GAD, IA-2 and ZnT8) signal pancreatic beta cell attack and are validated predictive biomarkers for T1D. Assays for detection of these autoantibodies are commercially available and have been used in multiple trials to predict progression to T1D. However, expansion efforts for T1D prevention have been greatly limited by the lack of a cost-effective, fast, reliable, and widely available assay for T1D autoantibodies detection in the general population. As the most meaningful natural history and prevention studies begin their screening in very early life, requirement of small volume sample for such test will be a key consideration especially when children are concerned. Using our nanoscience based pGOLD platform which provides femtomolar sensitivity and 6-log dynamic range for biomarker detection, Nirmidas Biotech. Inc. aims to develop and validate a fully automated, multiplexed assay for the diagnosis of T1D with sensitivity and specificity matching the current gold standard radioimmunoassay (RIA) done for clinical test, in a much faster, more cost-effective, lower complexity, smaller sample volume requirement and higher throughput format. Expanding on the prototype Phase I multiplexed T1D assay, the general strategy for achieving the Phase II project goals is to finalize the optimization of the analytical performance of the multiplexed T1D assay on pGOLD platform, followed by clinical validation of the assay with a large carefully chosen set of T1D and control samples. A fully automated system covering assay process and fluorescence reading with data acquisition/analysis/report will then be built and validated, which will facilitate FDA clearance and translation into clinical use of the pGOLD T1D test.

Public Health Relevance Statement:
Over three decades of research efforts involving over millions of individuals have demonstrated that T1D associated autoantibodies are diagnostic, and asymptotic children with multiple autoantibodies progress to symptomatic diabetes at a rate approximating 11% per year. Although initial study results highlighted improved T1D prevention with earlier diagnosis and initiation of therapy, these efforts are hampered by the non-availability of cost-effective T1D assays for identification of patients most likely to develop type 1 diabetes in the future. To provide better diagnostic tools for the T1D diagnosis and asymptotic population-based screening, we aim to develop and validate a fully automated, rapid, multiplexed T1D autoantibody assay, which matches the performance of current gold standard clinical test, and is cost-effective, easy to use, and requires small sample volume.

Project Terms:
4 year old; Antibodies; Antigens; assay development; Autoantibodies; base; Biological Assay; Biological Markers; Biotechnology; cell injury; Child; Childhood; Clinical; cohort; Computer software; cost effective; data acquisition; Data Set; Detection; Development; Diabetes autoantibodies; diabetes control; Diabetes Mellitus; Diabetes prevention; Diagnosis; Diagnostic; Disease; Early Diagnosis; Early identification; Enzyme-Linked Immunosorbent Assay; Fluorescence; Future; General Population; Genetic Risk; Goals; Gold; Human; Immunoglobulin G; improved; In Vitro; Incidence; Individual; Insulin; Insulin-Dependent Diabetes Mellitus; islet; Islets of Langerhans; Life; Liquid substance; Measures; multiplex detection; nanoscience; Nanotechnology; Natural History; non-diabetic; Non-Insulin-Dependent Diabetes Mellitus; novel; Patients; Performance; Phase; plasmonics; Population; population based; predictive marker; Prevalence; Prevention; Prevention strategy; Process; programs; Protocols documentation; prototype; Radioimmunoassay; Radioisotopes; Reader; Reading; Reporting; Research; research clinical testing; Risk; Robotics; Sampling; screening; Sensitivity and Specificity; Serum; Signal Transduction; Specificity; Specimen; Standardization; Structure of beta Cell of islet; System; Techniques; Testing; Time; tool; Translations; trend; Validation; Venipunctures; Work