Development of automated single cell manipulation and analysis techniques for rare cell applications

拟议的研究计划将为稀有单细胞开发新的操作和分析技术。单细胞分析是一个新兴的领域，由于它可以促进对活细胞的细胞和分子行为的准确研究，因此正在生命/健康科学中引起极大的兴趣。这将进一步加深我们对细胞可塑性、异质性、感染监测、自身免疫、药物输送、干细胞分析或癌细胞检测的了解--所有这些都是在单细胞水平上的。这些应用以及生命科学和健康研究中的其他进步推动了开发新技术和工具的需求，这些新技术和工具可以快速执行更复杂和更准确的单细胞分析。 近期的目标将是在单个细胞分辨率下分离和鉴定外周血中罕见的循环肿瘤细胞(CTCs)。CTCs是从血液中发现的原发肿瘤中排出的肿瘤细胞，被认为是继发性肿瘤(即转移)的种子细胞。因此，识别和鉴定血液中的CTCs有望提供一种识别已发展为转移性疾病的患者的手段，并提供一种早期检测方法。此外，分析CTCs的特定细胞和分子变化有可能确定有效的治疗方法，因为肿瘤细胞的特定特征决定了所使用的治疗策略。因此，人们对从血液样本中检测、分离和表征CTCs的更好方法非常感兴趣。该研究计划将首先针对转移性前列腺癌的CTCs。在加拿大，估计每年将有2.5万名男性被诊断出患有这种疾病，其中4000人将死于这种疾病。最近的研究表明，与前列腺特异性抗原(PSA)相比，CTC计数是更有效的生存早期预测指标。 拟议的研究计划将导致创建用于自动化单细胞分析的新型机器人辅助技术，这些技术与健康研究中的科学发现紧密联系并使之成为可能。这是一项高风险、高收益的研究，有可能在研究和诊断疾病以及研究新的药物靶标识别方面取得变革性的技术进步。

The proposed research program will develop novel manipulation and analysis techniques for rare single cells. Single cell analysis is an emerging field that is gaining significant interest in life/health sciences since it can facilitate accurate studies of cellular and molecular behaviours of living cells. This will further our knowledge about cell plasticity, heterogeneity, monitoring infections, auto-immunity, drug delivery, stem cell analysis, or cancer cell detection-all at the single cell level. These applications and other advances in life sciences and health research are driving the need to develop new techniques and tools that can rapidly perform more complex and accurate single cell analysis. The immediate goal will be to isolate and characterize rare circulating tumor cells (CTCs) in the peripheral blood at single cell resolution. CTCs are neoplastic cells shed from primary tumors that are found in blood and are believed to seed secondary tumors (i.e. metastasis). Therefore, identifying and characterizing CTCs in blood has the prospect of providing a means of identifying patients who have developed metastatic disease and provide an early detection method. Furthermore, analysis of CTCs for specific cellular and molecular changes has the potential of identifying effective therapies as specific features of tumor cells determine the therapeutic strategy used. Thus, there is much interest in better methods to detect, isolate, and characterize CTCs from blood samples. The research program will first target the CTCs in metastatic prostate cancer. In Canada, an estimated 25,000 men will be diagnosed with the disease every year and 4,000 will die from it. Recent studies suggest CTC count to be a more powerful early predictor of survival than prostate-specific antigen (PSA). The proposed research program will result in the creation of novel robotic-assisted techniques for automated single cell analysis that are tightly linked to and enabling of scientific discoveries in health research. This is a high-risk, high-benefit research that has potential for transformative technological advances in studying and diagnosing diseases and researching novel drug target identification.