A miniaturized neural network enabled nanoplasmonic spectroscopy platform for label-free cancer detection in biofluids

项目总结/摘要 用于早期检测和监测癌症的现有技术方法是侵入性的、耗时的， 昂贵，或经常不准确，这阻碍了常规筛查的风险患者，以提高生存率 rates.对在微创或非侵入性生物流体中循环的癌细胞的多重检测，例如 唾液、血浆或汗液可以提供显著的临床和经济效益。金属及相关 循环生物标志物是结构独特的元素，在红外（IR）中具有独特的吸收指纹 电磁波谱的一部分。提供多重代谢物检测的常用方法， 例如质谱（MS）、拉曼光谱和傅里叶变换红外（FTIR）光谱， 是昂贵的并且难以实现。另一方面，廉价的小型化电化学技术 缺乏特异性、敏感性、简便性，并且受到有限的多路复用的影响。便携式技术能够快速和 早期/晚期癌症的准确诊断并不容易获得。 为了应对这一挑战，我们的多学科团队提出了一种创新的神经网络癌症 基于等离子体纳微机电系统的NNECS液体活检平台 （NMEMS）来诊断和监测早期/晚期头颈癌（HNC）。而不是针对个人 为了检测唾液、血浆和汗液中的代谢物，我们建议将唾液、血浆和汗液的整个IR光谱作为生物标志物进行处理。 我们的重点是头颈癌（HNC），这是一种高度代谢性疾病， 更好的诊断信息将大大改善结果。我们的平台结合了IR NMEMS传感器， 准确地检测红外光谱指纹与神经网络（NN）框架，以找到适当的 这将为高度多路复用的小型化生物传感器的设计提供信息。 我们将在五个关键组成部分的框架内采取一种新颖的跨学科方法：（一）收集和 分析（FTIR，MS，组织病理学/成像）来自大量早期/晚期的生物流体（唾液，汗液，血液） 分期HNC患者和健康受试者每年;（ii）开发强大的NN架构和诊断工具 用于将早期/晚期HNC样品与对照分离，考虑来自每个个体的IR数据流 生物流体以及它们的潜在组合;（iii）使用等离子体激元阵列开发NNECS平台 NMEMS靶向通过ML算法解析的特定IR波段;（iv）确定NNECS早期/晚期癌症 在特异性、灵敏度和准确性方面的检测性能;以及（v）阐明哪些代谢物 驱动MS支持的癌症生物流体的IR吸收的变化。预期结果是 小型化、无标签、价格合理、准确的技术，能够从根本上提高早期诊断的能力， 阶段HNC以及复发HNC患者的监测。除此之外，NNECS还可适用于 诊断和监测广泛的代谢状况，包括许多类型的癌症，糖尿病， 心脏病

PROJECT SUMMARY/ABSTRACT State of the art methods for the early detection and monitoring of cancer are either invasive, time-consuming, expensive, or frequently inaccurate, which hinders the routine screening of at risk-patients to improve survival rates. The multiplexed detection of oncometabolites circulating in minimally or non-invasive biofluids, such as saliva, blood plasma, or sweat, could provide significant clinical and economic benefits. Metabolites and related circulating biomarkers are structurally unique elements with distinctive absorptive fingerprints in the infrared (IR) portion of the electromagnetic spectrum. Common approaches that provide multiplexed metabolite detection, such as mass spectrometry (MS), Raman spectroscopy, and Fourier transform infrared (FTIR) spectroscopy, are expensive and difficult to miniaturize. On the other hand, inexpensive miniaturized electrochemical techniques lack specificity, sensitivity, ease, and suffer from limited multiplexing. Portable technologies capable of rapid and accurate diagnostics of early/late-stage cancer are not readily available. To address this challenge, our multidisciplinary team proposes an innovative Neural Network Enabled Cancer Spectroscopy (NNECS) liquid biopsy platform based on plasmonic nano-micro electromechanical systems (NMEMS) to diagnose and monitor early/late-stage head neck cancer (HNC). Instead of targeting individual metabolites, we propose to process the entire IR spectrum of saliva, blood plasma, and sweat as a biomarker. Our focus is head and neck cancer (HNC), a highly metabolic disease where stratification of patients according to better diagnostic information would greatly improve outcomes. Our platform combines IR NMEMS sensors to accurately detect IR spectral fingerprints with neural network (NN) frameworks to find the appropriate combinations of spectral bands that will inform the design of highly multiplexed miniaturized biosensor. We will take a novel, interdisciplinary approach within the framework of five key components: (i) collecting and analyzing (FTIR, MS, histopathology/imaging) biofluids (saliva, sweat, blood) from a large number of early/late stage HNC patients and healthy subjects per year; (ii) developing powerful NN architectures and diagnosis tools for segregating early/late-stage HNC samples from controls, considering IR data streams from each individual biofluid as well as their potential combinations; (iii) developing a NNECS platform using arrays of plasmonic NMEMS targeting specific IR bands resolved by ML algorithms; (iv) determining NNECS early/late-stage cancer detection performance in terms of specificity, sensitivity, and accuracy; and (v) elucidating which metabolites drive the changes in the IR absorption of cancer biofluids supported by MS. The expected outcome is a miniaturized, label-free, affordable, and accurate technology able to radically improve the ability to diagnose early- stage HNC as well as the monitoring of recurrent HNC patients. Moving beyond, NNECS can be adapted for the diagnosis and monitoring of a wide range of metabolic conditions, including many types of cancer, diabetes, and heart-diseases.