- Biomechanics-Based Microfluidic Biochip for the Effective Label-Free Isolation and Retrieval of Circulating Tumor Cells

Abstract

Cancer is a genetic disease that manifests as abnormal cell proliferation and growth consequently impairs normal body functions. In 2008 alone, 7.6 million people died from the disease according to the World Health Organization (WHO) [1]. Furthermore, the lack of telltale signs at the disease onset limits the ability for the eradication or early treatment of cancer [2]. There is a need for improved techniques of cancer detection and monitoring in order to reduce and alleviate the burden imposed on patients and health-care systems by cancer. Circulating tumor cells (CTCs) are cancerous cells that enter the blood circulation during hematogenous metastasis, and multiple studies have demonstrated an association between these cells and disease activity [3-5]. The documented evidence for the presence of CTCs dates back to over a century [6], which veries the blood circulation as a means that allows transportation of tumor cells to other parts of the body. More recently, studies have demonstrated the presence of CTCs in patients with various metastatic carcinomas [7,8]. There have been numerous studies demonstrating that the number of CTCs in peripheral blood is an important prognostic indicator in metastatic breast, prostate, and colon cancers [9-12]. These studies have directly linked CTC count with disease20.1 Introduction ...................................................................................................................................355 20.2 Materials ...................................................................................................................................... 35720.2.1 Microdevice Fabrication .................................................................................................. 357 20.2.2 Experimental Setup and Apparatus Preparation ............................................................. 357 20.2.3 Blood Collection .............................................................................................................. 358 20.2.4 Cell Culture ..................................................................................................................... 358 20.2.5 Spiked Sample Preparation ............................................................................................. 359 20.2.6 Immuno•uorescence Staining to Identify CTCs ............................................................ 35920.3 Methods ........................................................................................................................................ 360 20.3.1 Biomechanical Approaches to Studying Cancer ............................................................. 360 20.3.2 Physical Isolation of CTCs ...............................................................................................36120.4 Results and Discussion ................................................................................................................. 362 20.4.1 Microdevice Efciency and Isolation Purity ................................................................... 362 20.4.2 Versatility of the Separation Technique and Limits of Detection ................................... 365 20.4.3 State of Retrieved Cancer Cells ....................................................................................... 366 20.4.4 Clinical Sample Processing ............................................................................................. 36720.5 Conclusions .................................................................................................................................. 369 Acknowledgments .................................................................................................................................. 369 References .............................................................................................................................................. 369progression, and there is emerging evidence for its use in prediction of treatment efcacy [13-16]. The isolation of CTCs from peripheral blood is more amenable to that of biopsies in terms of less invasiveness, patient acceptability, and increased frequency of tests to perform. Additionally, the isolation of CTCs provides a promising alternative source of tumor tissue for the detection and characterization of non-blood-related cancers. Thus, analyzing the blood specimens of patients which are routinely taken can be useful. The isolation, quantication, and study of these cells obtained from peripheral blood are thus of much interest.