Hybrid Microfluidic Microelectronic Sensing Systems for Early Detection of Infection and Inflammatory Disease

当前的新冠肺炎大流行表明，传染病可以多么迅速地在全球传播。毫无疑问，对于所有科学领域的研究人员来说，快速应对传染病的暴发，无论是复发的还是新颖的，都是最关键的挑战之一，包括那些在护理点(PoC)设备传感技术方面的研究人员。由于感染通常与发烧等可见症状同时发生，红外温度传感器(即PoC设备)正越来越多地用于机场、医院和其他公共场所，以更好地识别感染高危人群。然而，这是基于一种已知的症状--发烧--而许多感染病例往往没有明显的症状。这些没有症状的病例继续蔓延到其他人，并对公共安全构成威胁。总之，迫切需要一种新的PoC传感技术来检测与无症状甚至症状前感染相关的生物标志物。在这项研究计划中，我们将开发一种新型的POC设备来从唾液中分离口腔中性粒细胞(即白细胞)。然后可以分析这些细胞，以确定生物标记物水平和WBC的其他特征之间的相关性，以跟踪感染或疾病进展。这项研究将回答几个问题：是否有任何隐藏的感染症状，可以在家里使用便携式PoC传感器检测到？如何使用低成本、快速和准确的技术有效地从唾液中分离口腔白细胞？如何使用可靠、易用的传感技术来测量唾液WBC的水平和其他生理特征？在传染病暴发等紧急情况下，哪种微制造技术既能大规模生产，又能快速投放市场？可以开发哪个传感平台来研究唾液中的WBC的其他特征，以调查它们与炎症性疾病的相关性？我们将在我们的研究计划中解决上述问题，开发一种使用微流控技术和标准微电子集成电路的蜂窝接口系统，这是智能手机和计算设备中的核心技术。这项研究的长期目标是开发家庭便携式唾液WBC测试，以早期发现感染和疾病的症状，以便个人可以每天在家中监测自己的健康。这项研究项目的成功使我们能够开发能够迅速适应未来传染病爆发的传感技术。此外，拟议的传感技术将在早期检测其他炎症性疾病方面具有被证明的优势，例如牙周炎，或者对于大量患有免疫缺陷疾病的人来说，这些疾病阻止了身体与疾病作斗争。

The current COVID-19 pandemic has demonstrated how rapidly communicable diseases can spread across the globe. Undoubtedly, quickly responding to communicable disease outbreaks, whether recurring or novel, is one of the most critical challenges for researchers in all scientific areas, including those in Point-of-Care (PoC) device sensing technologies. As infection often occurs in parallel with visible symptoms, such as fever, infrared temperature sensors (i.e. PoC devices) are increasingly being used in airports, hospitals and other public places to better identify individuals at high-risk of infection. However, this is based on a known symptom - fever - and many infection cases often do not display visible symptoms. These asymptomatic cases continue to spread to others and pose a threat to public safety. In short, a novel PoC sensing technology is urgently needed to detect biomarkers associated with asymptomatic and even pre-symptomatic infection. In this research program, we will develop a novel PoC device to separate oral neutrophils (i.e. white blood cells, WBC) from saliva. These cells can then be analyzed to identify a correlation between biomarker levels, and other features of WBCs, to track infection or disease progression. This research will answer several questions: Are there any hidden symptoms of infection that can be detected using a portable PoC sensor at home? How can oral WBCs be efficiently isolated from saliva using low-cost, rapid and accurate techniques? How can the level and other physiological features of salivary WBCs be measured using reliable, easy-to-use sensing techniques? Which microfabrication technology has the capability of both mass production and fast delivery to the market in an urgent situation such as a communicable disease outbreak? Which sensing platform can be developed to study other features of WBCs in saliva to investigate their correlation with inflammatory diseases? We will address the above questions in our research program by developing a cellular interfacing system using microfluidic techniques and standard microelectronic integrated circuits, a core technology found in smartphones and computing devices. The long-term goal of this research is to develop at-home portable salivary WBCs tests for early detection of symptoms of infection and disease, so that individuals can monitor their health from home on a daily basis. The success of this research program enables us to develop sensing technology that can rapidly be adapted for future communicable disease outbreaks. Additionally, the proposed sensing technology will have proven advantages for early detection of other inflammatory diseases such as periodontitis, or for the significant number of people suffering from immunodeficiency disorders that are preventing the body from fighting disease.