An Ultrasonic System-on-a-chip for Early Cancer Diagnosis

当原发性肿瘤从最初开始的地方扩散到体内的另一个地方时，癌症就会危及生命。扩散过程称为转移，由扩散癌细胞形成的肿瘤称为转移性肿瘤。转移是诊断为浸润性癌症的患者死亡的主要原因。转移机制已被深入研究，但尚未完全理解。据报道，由原发性肿瘤脱落到血流中的肿瘤细胞，即循环肿瘤细胞（CTC），是癌症转移的种子。对CTC的研究，如其群体，从血液中分离，基因分型和表型是理解转移生物学的关键。CTC是极其罕见的，即使在转移性癌症患者中也是如此（大约十亿个正常血细胞中的一个计数），并且它们的分离在很大程度上受到技术限制。该项目将开发一种超声波片上系统（USC），用于基于CTC的机械特性（如尺寸，密度和可压缩性）从血液样品中分离CTC。将研究USC的参数数值模拟，以设计最佳的设备几何形状，灵敏度和吞吐量，以推进当前基于声学的传感器在微粒分离中的应用。USC应该能够操纵极低浓度的CTC，因为它们在1 mL血液样品中仅发现几种，但足以在癌症患者中接种继发性肿瘤。CTC的预期回收率超过90%，以实现USC在临床应用中的实施。微系统制造与超声技术将参与这个项目，以开发超声波系统芯片。对临床样本的初步研究将提供潜力，作为癌症研究的宝贵补充工具，特别是在早期癌症诊断和药物疗效评估方面。

A cancer becomes life-threatening when the primary tumour spreads from the place where it first started to another place in the body. The spreading process is called metastasis, a tumor formed by spreading cancer cells is called a metastatic tumor. Metastasis is the principal cause of death in patients diagnosed with invasive cancer. The metastatic mechanism has been intensively researched but not fully understood. It has been reported that tumour cells shed by the primary tumour to blood stream, namely circulating tumour cells (CTCs), are the seeds for cancer metastasis. Research on CTCs such as their population, isolation from the blood, genotyping, and phenotyping holds the key to understanding the biology of metastasis. CTCs are extremely rare, even in patients with metastatic cancer (approximately one count among a billion normal blood cells), and their isolation is greatly subject to technological constraints. This project will develop an ultrasonic system-on-a-chip (USC) for separating CTCs from blood samples based on CTCs' mechanical properties such as size, density, and compressibility. Parametric numerical simulations of the USC will be investigated to design optimum device geometry, sensitivity, and throughput in order to advance the current application of acoustic-based sensor in microparticle separation. The USC should be able to manipulate extremely low concentration of CTCs as they are found only several in 1-mL blood sample but sufficient for seeding secondary tumour in a cancer patient. The expected recovery rate of CTCs is more than 90% in order to realise the implementation of the USC in clinical applications. Microsystem fabrication with ultrasound techniques will be involved in this project to develop the Ultrasonic System on a Chip. Preliminary studies of clinical samples will take place to offer the potential to serve as invaluable supplemental tool in cancer research, especially in early cancer diagnosis and drug efficacy assessment.