SBIR Phase II: Absolute protein quantitation in in vitro diagnostics for gut inflammation

小型企业创新研究(SBIR)第二阶段项目的更广泛影响是推进临床方法，解决年龄和种族相关的广泛生理差异。过去几十年来广为人知的是，缺乏针对早产儿疾病的医疗解决方案，这些早产儿的母亲在社会经济上存在严重的不平等。例如，坏死性小肠结肠炎(NEC)是早产儿常见的、往往是致命的胃肠道急症，对非裔美国婴儿的影响不成比例。这种疾病不仅困扰了医生和护士200年，而且这些新生儿紧急情况也让几乎所有早产护理人员感到恐惧，因为它的高死亡率。由于反复进行X射线检查、手术、住院时间较长以及幸存者的长期并发症，该公司在美国的医疗保健每年需要30亿美元。对NEC的早期准确诊断测试将是早产儿重症监护的颠覆性范式转变：它将使医疗干预更加有效，降低疾病进展的风险，每年减少数亿医疗保健费用，并降低死亡率。拟议中的项目将为诊断测试开发必要的试剂，使其能够检测到对肠道健康起作用的婴儿蛋白质。绝对定量是在实验、实验室和测试平台之间进行数据解释和验证的先决条件。研究目标针对关键的技术障碍：(1)确定临床环境中定量宿主生物分子的最佳参考标准；(2)了解这些参考标准在人类群体高度变异的背景下的使用限制。将用各种方法对原生和重组候选进行比较和分析。预期结果是特定于年龄的参考标准，适用于最脆弱和最小的患者的诊断，并且可以被监管利益相关者接受。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is to advance clinical methods that address the extensive physiological variation that is age- and race-dependent. Well-publicized over the last few decades is the lack of healthcare solutions for diseases in preemie babies, who are born to mothers with significant socioeconomic inequalities. Case in point, necrotizing enterocolitis (NEC) is a common and often fatal gastrointestinal, or gut, emergency in premature infants that disproportionately affects African American babies. The disease has not only confounded doctors and nurses for 200 years, but also these neonatal emergencies are also frightening to almost all preemie care providers due to its high mortality rate. Its healthcare in the US requires $3 billion annually due to repeated x-ray testing, surgery, longer hospital stays, and long-term complications of its survivors. An early and accurate diagnostic test for NEC would be a disruptive paradigm shift in preemie intensive care: it would enable medical intervention to be more effective, reduce risk of disease progression, decrease medical care expenses by hundreds of millions annually, and lower mortality.The proposed project will develop requisite reagents for a diagnostic test that will enable detection of infant proteins that play a role in gut health. Absolute quantitation is a prerequisite for data interpretation and validation between experiments, laboratories, and testing platforms. Research objectives are directed toward critical technical hurdles: (1) determination of optimal reference standard to quantitate host biomolecules in clinical settings and (2) understanding the usage limitations of these reference standards in the background of high variation in the human population. Native and recombinant candidates will be compared and analyzed with various methods. Anticipated results are reference standards that are age-specific for diagnostic use in the most fragile and smallest patients and that are acceptable to regulatory stakeholders.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.