Microfluidic diagnostic (μDX) technologies miniaturize sensors and actuators to the length-scales that are relevant to biology: the micrometer scale to interact with cells and the nanometer scale to interrogate biology's molecular machinery. This miniaturization allows measurements of biomarkers of disease (cells, nanoscale vesicles, molecules) in clinical samples that are not detectable using conventional technologies. There has been steady progress in the field over the last three decades, and a recent burst of activity catalyzed by the COVID-19 pandemic. In this time, an impressive and ever-growing set of technologies have been successfully validated in their ability to measure biomarkers in clinical samples, such as blood and urine, with sensitivity and specificity not possible using conventional tests. Despite our field's many accomplishments to date, very few of these technologies have been successfully commercialized and brought to clinical use where they can fulfill their promise to improve medical care. In this paper, we identify three major technological trends in our field that we believe will allow the next generation of μDx to have a major impact on the practice of medicine, and which present major opportunities for those entering the field from outside disciplines: 1. the combination of next generation, highly multiplexed μDx technologies with machine learning to allow complex patterns of multiple biomarkers to be decoded to inform clinical decision points, for which conventional biomarkers do not necessarily exist. 2. The use of micro/nano devices to overcome the limits of binding affinity in complex backgrounds in both the detection of sparse soluble proteins and nucleic acids in blood and rare circulating extracellular vesicles. 3. A suite of recent technologies that obviate the manual pre-processing and post-processing of samples before they are measured on a μDX chip. Additionally, we discuss economic and regulatory challenges that have stymied μDx translation to the clinic, and highlight strategies for successfully navigating this challenging space.

中文翻译：

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将微流控诊断芯片推向临床应用：当前挑战与机遇回顾

微流控诊断 (μDX) 技术将传感器和执行器小型化至与生物学相关的长度尺度：微米尺度用于与细胞相互作用，纳米尺度用于询问生物学的分子机制。这种小型化可以测量临床样本中使用传统技术无法检测到的疾病生物标志物（细胞、纳米级囊泡、分子）。过去三十年来，该领域取得了稳步进展，最近在 COVID-19 大流行的推动下，该领域的活动激增。目前，一系列令人印象深刻且不断增长的技术已成功验证其测量临床样本（例如血液和尿液）中生物标志物的能力，其敏感性和特异性是使用传统测试无法实现的。尽管迄今为止我们的领域取得了许多成就，但这些技术很少成功商业化并应用于临床，从而实现改善医疗保健的承诺。在本文中，我们确定了我们领域的三个主要技术趋势，我们相信这些趋势将使下一代 μDx 对医学实践产生重大影响，并为从外部学科进入该领域的人提供了重大机会：1.下一代高度多元化的μDx技术与机器学习相结合，可以解码多种生物标志物的复杂模式，为临床决策点提供信息，而传统的生物标志物不一定存在。2. 利用微纳器件克服复杂背景下结合亲和力的限制，检测血液中稀疏的可溶性蛋白和核酸以及稀有的循环细胞外囊泡。3. 一套最新技术，可避免在 μDX 芯片上测量样品之前对样品进行手动预处理和后处理。此外，我们还讨论了阻碍 μDx 向临床转化的经济和监管挑战，并重点介绍了成功应对这一充满挑战的领域的策略。