Development of a plasmonic-based multiplexed platform for Diagnosis and Screening of Type 1 Diabetes and related Auto-Immune Diseases

 描述(申请人提供)：世界卫生组织预测，全球糖尿病病例将从2005年的2.17亿例增加到2030年的3.66亿例[1]。儿童1型糖尿病或自身免疫性糖尿病(T1D)的发病率正以每年3%的速度增长，预计2004至2020年间将增长70%，而儿童2型糖尿病(T2D)的发病率也一直在指数级增长，部分原因是全球肥胖流行。这些疾病的诊断变得越来越困难。目前，对新入院患者的T1D诊断和筛查测试是通过缓慢且昂贵的放射免疫分析(RIA)进行的，延误了最终诊断和及时治疗。RIA测试可能需要长达两周的时间才能做出诊断，但在某些情况下，需要临床干预才能在24小时或更短时间内诊断出T1D。由于需要放射性同位素的产生和检测，世界上资源有限的发展中国家和地区无法获得T1D测试。此外，自身抗体阳性的潜在自身免疫性糖尿病成人(LADA)病例也很常见，占成年2型糖尿病患者的不小部分。成人糖尿病患者的抗体检测和筛查也将为LADA患者的管理和治疗提供有价值的信息和指导。值得注意的是，在T1D患者中，乳糜泻和自身免疫性甲状腺疾病(ATD)的患病率明显较高，这两种疾病被认为是相关疾病。在美国，自身免疫性甲状腺疾病发生在约15-30%的T1D患者中，乳糜泻发生在4-9%的T1D患者中。我们建议开发一种同时诊断T1D、腹腔病和ATD的多重自身免疫抗体芯片并进行临床测试。该芯片将利用临床上发现的现有仪器，通过Nirmidas Biotech提供的独特信号增强技术pGOLD提供快速、基于荧光的诊断测试。PGOLD芯片将在短短1-2小时内检测出患者血清中指示T1D、腹腔疾病和ATD的自身抗体，其性能与RIA相同。该项目将用150个患者血清样本测试pGOLD芯片，作为获得监管部门批准和该芯片商业化的第一步。

 DESCRIPTION (provided by applicant): 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.