[89] used a microfluidic device with four parallel chambers fabricated using PDMS soft lithography to culture rat C6 Glioma cells, as shown in Determine 9

[89] used a microfluidic device with four parallel chambers fabricated using PDMS soft lithography to culture rat C6 Glioma cells, as shown in Determine 9. field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1) Lung; (2) Bone marrow; (3) Brain; (4) Breast; (5) Urinary system (kidney, bladder and prostate); (6) Intestine; and (7) Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based SAR191801 on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heartCliverCintestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET) of anticancer drugs and more realistically recapitulate tumor in vivo-like microenvironment. strong class=”kwd-title” Keywords: tumor-on-a-chip, cancer in microfluidics, drug efficacy testing, in vitro assays, concentration gradient generators, microchip cell culture, spheroids, tumor microenvironment 1. Introduction Though described as a modern disease, cancer, originally named by Hippocrates (460C370 BC), is one of the oldest diseases of human beings as well as other animals. Edwin Smith Papyrus explains breast tumors more than 5000 years ago, with there is no treatment under the treatment options [1]. This disease seems to be hidden under the shadows of other fatal diseases and has been more highlighted in the last 100 years as one of the leading causes of death worldwide. Its occurrence is usually directly related to patients age and SAR191801 thus illustrates the underlying reason of its frequency in recent years, with over 80-12 months life spans. Throughout this paper, we concise the term tumor to malignant neoplasms showing six hallmarks of cancerous cells including [2]: (1) capability of cells to grow and divide without stimulus signals; (2) ignoring anti-growth signals; (3) inability to undergo apoptosis; (4) gaining immortality potential; (5) producing extra blood vessels (angiogenesis) and (6) invading tissue and spreading to other organs (metastasis). Chemotherapy, with surgical excision, radiotherapy and immunotherapy is among the most common curing options. However, in most cases, recurrence of tumor as well as its metastasis to other tissues has made treatment ineffective. Conventionally, in preclinical drug development, two methods of animal work and/or two-dimensional (2D) or three-dimensional (3D) laboratory cell cultures are used to evaluate the efficacy and safety of a drug candidate in vivo and in vitro, respectively. While animal study provides a systemic environment for the tumor growth, it lacks the realistic response of human body. On the other hand, static monolayer 2D and more realistic 3D laboratory cell culture plates lack the systemic nature of living cells. It SAR191801 highlights the importance of an alternative platform to further understanding the complex nature of this disease as well as to develop effective therapeutic agents. Microfluidics, which is a study of fluid flow in micron-size domains, proves to be an effective technology in cancer study both in vivo and in vitro. For in vivo study, it is related to targeted drug delivery systems using wise carriers [3,4,5]. With the emerging SAR191801 concept of lab-on-a-chip, in vitro microfluidic devices are closely linked to tissue engineering and regenerative science promising a great step toward personalized medicine [6]. One of the most SAR191801 important features of a cancerous tumor, which highly affects its therapeutic response to anti-cancer drugs, is its complex microenvironment including blood vessels, fibroblasts immune cells and extracellular matrix (ECM). In addition, the above-mentioned hallmarks of Rabbit Polyclonal to OR2Z1 malignant neoplasms and other special characteristics of tumor such as Enhanced.