Terahertz Lab-on-a-Chip for Bio-liquid Analysis

全球对新技术的需求日益增长，这些技术能够提供快速准确的医疗诊断，并改善患者的预后。在微流体和微电子学的显著进步的帮助下，生物传感器领域已经大幅增长，以满足这一需求。这场微技术革命导致了以芯片实验室(LOC)形式的生物传感器的实现，它可以在单个芯片上对微量液体样本进行一次或多次实验室分析。这种分析可以采取许多不同的形式，如化学、声学、低频电学或光学。太赫兹频率范围(100 GHz到3 THz)是生物系统电磁分析的一个新兴领域。对于生物液体，它能够探测生物分子-溶剂体系中存在的旋转和振动模式，并且对生物分子的水合、温度、结合和构象状态高度敏感。尽管有这些显著的传感优势，但太赫兹波的波长相对较长，这限制了可以探测到的最小可探测物体或液体体积，其大小可与波长立方体相当。在这项工作中，我们建议将多个太赫兹谐振器与微流控系统相结合，以创建能够快速传感自由流动的生物液体的LOC。谐振器被设计成将测量电场集中到与细胞大小相当的体积，克服了衍射限制，并允许对皮升数量的生物液体和单个细胞进行电磁分析。该LOC将为细胞、极少量的各种细胞成分(例如蛋白质、DNA和RNA)和其他感兴趣的生物分子的科学研究提供一个测量平台。研究计划旨在推动目前太赫兹液体传感在灵敏度(10倍)、最小样本量和低成本制造方面的最先进水平，以在医疗诊断和临床应用中开辟新的传感和诊断机会。虽然主要针对生物液体的分析，但开发的单芯片实验室设备也将被证明对有毒和爆炸性液体的分析以及气体传感有用。

There is an increasing global demand for new technologies which deliver rapid and accurate medical diagnostics and lead to improved patient outcomes. The biological sensors field has grown dramatically to meet this demand, aided by significant improvements in microfluidics and microelectronics. This revolution in micro-technology has led to the realisation of biological sensors in the form of a lab-on-a-chip (LOC) that can perform one or more lab analyses of minute quantities of liquid samples on a single chip. This analysis can take many different forms such as chemical, acoustic, low-frequency electrical or optical.The terahertz frequency range (100 GHz to 3 THz) is an emerging area for the electromagnetic analysis of biological systems. For biological liquids, it is capable of probing rotational and vibrational modes present in biomolecule-solvent systems and is also highly sensitive to biomolecular hydration, temperature, binding and conformational states. Despite these significant advantages for sensing, terahertz waves suffer from a relatively long wavelength which limits the smallest detectable object or liquid volume that can be sensed to a size comparable to a wavelength cubed. This size limit, called the diffraction limit, is significantly larger than many objects of interest such as a biological cell.In this work, we propose to integrate multiple terahertz resonators with a microfluidic system to create a LOC capable of rapidly sensing free-flowing bio-liquids. The resonators are designed to concentrate the measuring electric field down to a volume comparable to a cell size, overcoming the diffraction limit, and permitting the electromagnetic analysis of picolitre quantities of biological liquids and individual cells. This LOC will function as a measurement platform for scientific studies of cells, extremely small quantities of various cell components (e.g. proteins, DNA and RNA) and other biomolecules of interest.The research programme intends to push the current state-of-the-art in terahertz liquid sensing in terms of sensitivity (10x), minimum sample volume and low-cost fabrication to open up new sensing and diagnostic opportunities in point-of-care diagnosis and clinical applications. While primarily directed towards the analysis of bio-liquids, the lab-on-a-chip devices developed will also prove useful for the analysis of toxic and explosive liquids, as well as gas sensing.