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

当原发肿瘤从最初开始的地方扩散到身体的另一个地方时，癌症就会危及生命。扩散的过程称为转移，由癌细胞扩散形成的肿瘤称为转移性肿瘤。转移是被诊断为浸润性癌症的患者的主要死亡原因。其转移机制已被广泛研究，但尚未完全了解。已有报道称，原发肿瘤释放到血流中的肿瘤细胞，即循环肿瘤细胞(CTCs)，是肿瘤转移的种子。对CTCs的研究，如其种群、血液分离、基因分型和表型分析，是了解转移生物学的关键。CTCs非常罕见，即使是在转移性癌症患者中也是如此(大约在10亿个正常血细胞中有一个)，而且它们的分离受到技术的极大限制。该项目将开发一种超声波芯片系统(USC)，用于根据CTCs的机械特性(如大小、密度和可压缩性)从血液样本中分离CTCs。为了推进当前声基传感器在微粒分离中的应用，将对超临界流体的参数数值模拟进行研究，以设计最优的器件几何形状、灵敏度和吞吐量。南加州大学应该能够处理极低浓度的CTCs，因为在1毫升的血液样本中只发现几种CTCs，但足以在癌症患者体内种植继发性肿瘤。预期CTCs回收率在90%以上，才能实现USC在临床上的应用。利用超声技术制造微系统将参与到这一项目中，以开发单芯片超声系统。将对临床样本进行初步研究，以提供在癌症研究中作为宝贵补充工具的潜力，特别是在癌症早期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.