Single cell analysis using imaging cytometry for a better understanding of critical diseases

微流体可以定义为处理少量液体的科学和技术。微流体装置通常涉及微米尺寸的通道网络，为生物细胞的精确操作提供理想的环境，例如用于检测或分选应用。因此，各种各样的设计，最常见的是小占地面积（~ cm 2），已经被设计成解决紧迫的医疗挑战，从癌细胞或病原体检测、基因递送或创建“芯片上的器官”等等。对于目前的工作，感兴趣的细胞是血细胞。通常在临床环境中监测血细胞，由此某些亚群（例如免疫细胞）的比例失调可能指示疾病。微流体技术的最新进展表明，除了细胞数量之外，还可以精确监测血细胞形态和变形能力，例如由于COVID 19引起的疾病变化。开发有助于更好地了解这些细胞变化的工程创新可以为患者监测，诊断和治疗提供新的途径。该项目的目标是领导开发一套小型化，基于微流体的设备，能够根据其形态和机械特征以高通量分选血细胞。将使用最先进的变形性细胞仪结合新的成像方法（例如，使用单光子雪崩二极管）进行血细胞表征。然后将设计和制造定制的微流体装置，以基于识别的特征（例如红细胞的一定变形性范围）分离细胞。

Microfluidics can be defined as the science and technology of handling small amounts of liquids. Microfluidic devices typically involve networks of channels in the micrometre size, offering an ideal environment for precise manipulation of biological cells, e.g. for detection or sorting applications. A large variety of designs, most commonly with a small footprint (~cm2), have consequently been engineered to tackle pressing medical challenges, from cancer cells or pathogens detection, gene delivery or to create "organs-on-a-chip" to mention a few. For the current work, cells of interest are blood cells. Blood cells are commonly monitored in clinical settings, whereby disproportion of a certain subpopulation (e.g. immune cells) might be indicative of a disease. Recent advances in microfluidic technologies have shown that beyond cell numbers, blood cell morphology and deformability can also be precisely monitored, with identifiable changes in disease for example due to COVID 19. Developing engineering innovations that could help better understand these cellular changes can offer a new route for patient monitoring, diagnosis and treatment. The goal of this project is to lead the development of a suite of miniaturized, microfluidic-based devices capable of sorting blood cells according to their morphological and mechanical features at high throughput. Blood cell characterization will be performed using a state-of-the-art deformability cytometer combined with new imaging approaches (e.g. using single-photon avalanche diodes). Bespoke microfluidic devices will then be designed and manufactured to separate cells based on identified features (for instance a certain deformability range of red blood cells).