Qudus Hamid Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, PA 19104 e-mail: qh25@drexel.edu Chengyang Wang Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, PA 19104 Fabrication of Biological Microfluidics Using a Digital Microfabrication System Yu Zhao Mechanical Engineering and Biomanufacturing Research Institute, Tsinghua University, Beijing 100000, China Jessica Snyder Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, PA 19104 Wei Sun1 Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, PA 19104; Mechanical Engineering and Biomanufacturing Research Institute, Tsinghua University, Beijing 100000, China; Shenzhen Biomanufacturing Engineering Laboratory, Shenzhen, Guangdong 518021, China e-mail: sunwei@drexel.edu Micro-electromechanical systems (MEMS) technologies illustrate the potential for many applications in the field of tissue engineering, regenerative medicine, and life sciences. The fabrication of tissue models integrates the multidisciplinary field o f life sciences and engineering. Presently, monolayer cell cultures are frequently used to investigate poten tial anticancer agents. These monolayer cultures give limited feedback on the effects of the micro-environment. A micro-environment, which mimics that of the target tissue, will eliminate the limitations of the traditional mainstays o f tissue research. The fabrication of such micro-environment requires a thorough investigation of the actual target organ, and or tissue. Conventional MEMS technologies are developed for the fabrication of inte grated circuits on silicon wafers. Conventional MEMS technologies are very expensive and are not developed for biological applications. The digital micromirroring microfab rication (DMM) system eliminates the need for an expensive chrome mask by incorporat ing a dynamic mask-less fabrication technique. The DMM is designed to utilize its digital micromirrors to fabricate o f biological devices. This digital microfabrication system pro vides a platform for the fabrication of economic biological microfluidics that is specifi cally designed to mimic the in vivo conditions of the tissue of interest. Investigations portrayed in this paper demonstrate the DMM capabilities to develop biological micro- fluidics. Though the applications of the DMM are extensive, the simple sinusoidal micro- fluidic characterized in this paper illustrates the DMM capabilities to develop biological microfluidic chips. [DOI: 10.1115/1.4028419] 1 Introduction There is an overwhelming need for substitutes to repair tissues and organs because of disease, trauma, or congenital problems. In the U.S. alone, as many as twenty million patients per year suffer from various organs and tissue related maladies caused by bums, skin ulcers, diabetes, and connective tissue defects which include bone and cartilage damage. More than eight million surgical pro- cedures are performed annually to treat these cases, over 70,000 people are on transplant waiting lists, and an additional 100,000 patients die due to the lack of appropriate organs [1-3]. Scientists are working around the clock to develop pharmaceuticals and tis- sue replacements that would allow humans to live longer lives. However, many of these developments require tremendous inves- tigation on its effects on humans. Quite often, the use of animal and human models is limited by the feasibility of testing proto- cols, availability, and ethical anxieties [4,5], MEMS technologies have been very attractive and demonstrate the potential for many applications in the field of tissue engineering, regenerative medi- cine, and life sciences. These fields bring together the multidisci- plinary field of engineering and integrated sciences to fabricate tissue models that aid the exploration, generation, or regeneration 'Corresponding author. Contributed by the Manufacturing Engineering Division of ASME for publication in the Journal of Manufacturing Science and E ngineering . Manuscript received February 27, 2014; final manuscript received August 19, 2014; published online October 24, 2014. Assoc. Editor; Joseph Beaman. of organic tissues and organs [6-8], MEMS were first introduced on conventional semiconductor materials, and since then, MEMS have been utilized in many other fields with great success [9-11]. The DMM system will give scientists the capabilities to develop models that can be utilized to characterize new pharma- ceuticals, tissue replacements, and develop models to study fatal disease such as cancers and tumors [12-14]. This biologically inspired microfabrication system has the potential to develop criti- cal three-dimensional models for the investigation of various tis- sue models and biological sensors. Three-dimensional biological models are preferred for in vitro investigation since these models eliminate the limitations of traditional mainstay two-dimensional models [15,16]. The DMM has the capabilities to fabricate many advantageous devices. Amongst them, microfluidics systems have the most tissue engineering, regenerative medicine, and life scien- ces applications to develop in vitro tissue models. Unlike conventional microfabrication techniques, the DMM eliminates the need for mask by incorporating a dynamic mask-less fabrication technique [17-20], Since the DMM system can develop models on a microscale level, this would make the fabri- cation of tissue constructs and biological investigation more eco- nomic; requiring less reagents, cells, and allow for consistency in experimental analysis to due limited interactions with the end user [21-23]. The DMM system is specifically designed for the develop- ments of biologically inspired devices, which includes, but are not limited to, biosensors, Lindenmayer systems, and micro-organs. Figure 1 shows and outline of the application potential of the Journal of Manufacturing Science and Engineering Copyright © 2014 by ASME DECEMBER 2014, Vol. 136 / 061001-1