Multi-Technique Bio-Analytical Investigation at the Single / Sub-Cellular Level Using a New Lab-On-A-Chip Technology Platform

世纪“硅芯片”工业的进步导致了新的微芯片处理技术的发展，这些技术允许电子和机械设备的持续微型化。这些进步被“芯片上”工具所采用，并为“芯片上”工具做出了贡献，从而使生物技术领域的知识和发明得到了巨大的提升。生物芯片是一种聚合物，玻璃或硅芯片，具有集成的设备和功能，可用于更好地了解人类发生的生化过程。这些新的知识和信息可以用于开发新的或更好的疾病治疗方法。最近有一个研究驱动器集成“芯片上”所有必要的传感器，微流体和分析工具所需的特定生物实验，在这种情况下，芯片可以被认为是一个独立的实验室。这项技术被称为芯片实验室（LOAC），在健康、技术和表面科学等不同科学学科的知识方面有着巨大的发展空间。生物技术产业对健康和全球经济做出了非常重要的贡献，例如DNA微阵列的发明。从事武装冲突法领域工作的研究小组正在集中大量的研究工作，研究能够在单细胞或亚细胞一级进行生物调查的各种技术。这些芯片需要能够按类型对细胞进行分类，将它们分开，并以受控的方式将它们输送到实验微型站点进行实验。新的工具现在正在商业化，可以分析细胞在微观网站同时结合“自上而下”的AFM力测量和成像与“自下而上”的先进光学调查。在使用AFM和光学分析技术相结合的情况下，由于所需的透明特性，所使用的LOAC技术必须是玻璃基的。这已经阻止了基于硅芯片的LOAC技术的使用，该技术将允许开发新的传感器功能，并且例如细胞的介电泳控制将在“芯片上”执行，从而减小尺寸和成本。制造和测试一种新型的硅芯片实验室（LOAC）结构，该结构具有光学透明特性，允许多技术单一或子技术，使用AFM和落射荧光显微镜进行细胞调查和分析。使用互补金属氧化物半导体（CMOS）兼容的工艺来制造新的LOAC结构，使未来的“芯片上”集成的分析技术与集成硅芯片技术的处理能力相结合的范围。这项研究将提供一个新的技术平台，可以通过未来的创新来开发新的工具，从而更好地了解支持许多疾病状态的免疫反应，包括过敏，糖尿病和癌症。

Advances in the 'silicon chip' industry during the 20th century led to the development of new microchip processing technologies that have allowed the continued miniaturisation of electronic and mechanical devices. These advances were adopted by and contributed to 'on-chip' tools to enable the massive boost in knowledge and invention within the Biotechnology area. A Biochip is a polymer, glass or silicon chip with integrated devices and features that can be used to better understand biochemical processes that occur in human beings. This new knowledge and information can be then used to develop new or better treatments for diseases. More recently there has been a research drive to integrate 'on-chip' all the necessary sensors, micro-fluidics and analysis tools required for specific biological experiments, in this case the chip can be considered as a self contained laboratory. This technology is called Lab-On-A-Chip (LOAC) and has tremendous scope to achieve further advances in knowledge across differing scientific disciplines such as health, technology and surface science. The biotechnology industry has made highly significant contributions to health and the global economy with the invention of the DNA microarray for example. Research groups working in the LOAC area are focusing significant research effort into various technologies that allow biological investigation at the single cell or sub-cellular level. These chips require the ability to sort cells by type, separate them and deliver them in a controlled manner to an experimental micro-site for experimentation. New tools are now becoming commercially available that can analyse the cells at the micro-site simultaneously combining 'top down' AFM force measurement and imaging with 'bottom up' advanced optical investigation. Where combined AFM and optical analytical techniques have been used the LOAC technologies used have been required to be glass based due to the required transparent characteristic. This has prevented the use of silicon chip based LOAC technology that would allow the development of new sensor functions and for example the dielectrophoretic control of cells to be performed 'on-chip' reducing size and cost.This research program aims to design, fabricate and test a novel silicon Lab-On-A-Chip (LOAC) structure with optical transparent characteristics that allow multi-technique singular or sub-cell investigation and analysis using AFM and epi-fluorescence microscopy. The use of a Complementary Metal Oxide Semiconductor (CMOS) compatible process to fabricate the new LOAC structure enables scope for future 'on chip' integration of analytical techniques combined with the processing power of integrated silicon chip technology. This research will provide a novel technology platform that can be developed with future innovations leading to new tools and thereby better understanding of the immunological response that underpins many disease states including allergy, diabetes and cancer.