Research Papers

Fabrication of Biological Microfluidics Using a Digital Microfabrication System

[+] Author and Article Information
Qudus Hamid

Department of Mechanical
Engineering and Mechanics,
Drexel University,
Philadelphia, PA 19104
e-mail: qh25@drexel.edu

Chengyang Wang, Jessica Snyder

Department of Mechanical
Engineering and Mechanics,
Drexel University,
Philadelphia, PA 19104

Yu Zhao

Mechanical Engineering and
Biomanufacturing Research Institute,
Tsinghua University,
Beijing 100000, China

Wei Sun

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

1Corresponding author.

Contributed by the Manufacturing Engineering Division of ASME for publication in the JOURNAL OF MANUFACTURING SCIENCE AND ENGINEERING. Manuscript received February 27, 2014; final manuscript received August 19, 2014; published online October 24, 2014. Assoc. Editor: Joseph Beaman.

J. Manuf. Sci. Eng 136(6), 061001 (Oct 24, 2014) (7 pages) Paper No: MANU-14-1080; doi: 10.1115/1.4028419 History: Received February 27, 2014; Revised August 19, 2014

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 of life sciences and engineering. Presently, monolayer cell cultures are frequently used to investigate potential 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 of 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 integrated circuits on silicon wafers. Conventional MEMS technologies are very expensive and are not developed for biological applications. The digital micromirroring microfabrication (DMM) system eliminates the need for an expensive chrome mask by incorporating a dynamic mask-less fabrication technique. The DMM is designed to utilize its digital micromirrors to fabricate of biological devices. This digital microfabrication system provides a platform for the fabrication of economic biological microfluidics that is specifically designed to mimic the in vivo conditions of the tissue of interest. Investigations portrayed in this paper demonstrate the DMM capabilities to develop biological microfluidics. Though the applications of the DMM are extensive, the simple sinusoidal microfluidic characterized in this paper illustrates the DMM capabilities to develop biological microfluidic chips.

Copyright © 2014 by ASME
Your Session has timed out. Please sign back in to continue.


Arbor Research, 2004, “The Organ and Transplantation Network,” http://www.ustransplant.org
Starly, B., Lau, W., Bradbury, T., and Sun, W., 2006, “Internal Architecture Design and Freeform Fabrication of Tissue Replacement Structures,” Comput. Aided Des., 38(2), pp. 115–124. [CrossRef]
Almeida, H., Bártolo, P., and Ferreira, J., 2007, “Design of Scaffolds With Computer Assistance,” Modell. Med. Biol. VII, 12, pp. 157–166. [CrossRef]
Parnes, L. S., Sun, A. H., and Freeman, D. J., 1999, “Corticosteroid Pharmacokinetics in the Inner Ear Fluids: An Animal Study Followed by Clinical Application,” Laryngoscope, 109(7), pp. 1–17. [CrossRef] [PubMed]
Elliott, N. T., and Yuan, F., 2011, “A Review of Three-Dimensional In Vitro Tissue Models for Drug Discovery and Transport Studies,” J. Pharm. Sci., 100(1), pp. 59–74. [CrossRef] [PubMed]
Starly, B., 2006, “Biomimetic Design and Fabrication of Tissue Engineered Scaffolds Using Computer Aided Tissue Engineering,” Ph.D. dissertation, Drexel University, Philadelphia, PA.
Shor, L., 2008, “Novel Fabrication Development for the Application of Polycaprolactone and Composite Polycaprolactone/Hydroxyapotote Scaffolds for Bone Tissue Engineering,” Ph.D. dissertation, Drexel University, Philadelphia, PA.
Huang, G. Y., Zhou, L. H., Zhang, Q. C., Chen, Y. M., Sun, W., Xu, F., and Lu, T. J., 2011, “Microfluidic Hydrogels for Tissue Engineering,” Biofabrication, 3(1), p. 012001. [CrossRef] [PubMed]
Jo, B. H., Van Lerberghe, L. M., Motsegood, K. M., and Beebe, D. J., 2000, “Three-dimensional Micro-channel Fabrication in Polydimethylsiloxane (PDMS) Elastomer,” J. Microelectromech. Syst., 9(1), pp. 76–81. [CrossRef]
Ho, C. M., and Tai, Y. C., 1998, “Micro-electro-mechanical-systems (MEMS) and Fluid Flows,” Annu. Rev. Fluid Mech., 30, pp. 579–612. [CrossRef]
Spearing, S. M., 2000, “Materials Issues in Microelectromechanical Systems (MEMS),” Acta Mater., 48(1), pp. 179–196. [CrossRef]
Zhang, X., Wang, W., Yu, W., Xie, Y., Zhang, X., Zhang, Y., and Ma, X., 2005, “Development of an In Vitro Multicellular Tumor Spheroid Model Using Microencapsulation and Its Application in Anticancer Drug Screening and Testing,” Biotechnol. Prog., 21(4), pp. 1289–1296. [CrossRef] [PubMed]
Hassan, S. B., de la Torre, M., Nygren, P., Karlsson, M. O., Larsson, R., and Jonsson, E., 2001, “A Hollow Fiber Model for In Vitro Studies of Cytotoxic Compounds: Activity of the Cyanoguanidine CHS 828,” Anticancer Drugs, 12(1), pp. 33–42. [CrossRef] [PubMed]
Cowan, D. S., Hicks, K. O., and Wilson, W. R., 1996, “Multicellular Membranes as an In Vitro Model for Extravascular Diffusion in Tumours,” Brit. J. Cancer, Suppl., 27, pp. S28–S31.
Casciari, J. J., Hollingshead, M. G., Alley, M. C., Mayo, J. G., Malspeis, L., Miyauchi, S., Grever, M. R., and Weinstein, J. N., 1994, “Growth and Chemotherapeutic Response of Cells in a Hollow-Fiber In-Vitro Solid Tumor-Model,” J. Natl. Cancer Inst., 86(24), pp. 1846–1852. [CrossRef] [PubMed]
Friedrich, M. J., 2003, “Studying Cancer in 3 Dimensions—3-D Models Foster New Insights Into Tumorigenesis,” JAMA, 290(15), pp. 1977–1979. [CrossRef] [PubMed]
Xiang, D., and Arnold, M. A., 2011, “Solid-state Digital Micro-mirror Array Spectrometer for Hadamard Transform Measurements of Glucose and Lactate in Aqueous Solutions,” Appl. Spectrosc., 65(10), pp. 1170–1180. [CrossRef] [PubMed]
Adeyemi, A. A., Barakat, N., and Darcie, T. E., 2009, “Applications of Digital Micro-mirror Devices to Digital Optical Microscope Dynamic Range Enhancement,” Opt. Express, 17(3), pp. 1831–1843. [CrossRef] [PubMed]
Shin, W., Yu, B. A., Lee, Y. L., Yu, T. J., Eom, T. J., Noh, Y. C., Lee, J., and Ko, D. K., 2006, “Tunable Q-switched Erbium-doped Fiber Laser Based on Digital Micro-mirror Array,” Opt. Express, 14(12), pp. 5356–5364. [CrossRef] [PubMed]
Lu, Y., Mapili, G., Suhali, G., Chen, S., and Roy, K., 2006, “A Digital Micro-mirror Device-based System for the Microfabrication of Complex, Spatially Patterned Tissue Engineering Scaffolds,” J. Biomed. Mater. Res. Part A, 77(2), pp. 396–405. [CrossRef]
Gauvin, R., Chen, Y. C., Lee, J. W., Soman, P., Zorlutuna, P., Nichol, J. W., Bae, H., Chen, S., and Khademhosseini, A., 2012, “Microfabrication of Complex Porous Tissue Engineering Scaffolds Using 3D Projection Stereolithography,” Biomaterials, 33(15), pp. 3824–3834. [CrossRef] [PubMed]
Catros, S., Guillemot, F., Nandakumar, A., Ziane, S., Moroni, L., Habibovic, P., van Blitterswijk, C., Rousseau, B., Chassande, O., Amedee, J., and Fricain, J. C., 2012, “Layer-by-layer Tissue Microfabrication Supports Cell Proliferation in vitro and in vivo,” Tissue Eng., Part C, 18(1), pp. 62–70. [CrossRef]
Andersson, H., and van den Berg, A., 2004, “Microfabrication and Microfluidics for Tissue Engineering: State of the Art and Future Opportunities,” Lab Chip, 4(2), pp. 98–103. [CrossRef] [PubMed]
Starly, B., and Sun, W., 2007, “Internal Scaffold Architecture Designs Using Lindenmayer Systems,” J. Comput. Aided Des. Appl., 4, pp. 395–403. [CrossRef]
Nederman, T., Acker, H., and Carlsson, J., 1983, “Penetration of Substances Into Tumor Tissue: A Methodological Study With Microelectrodes and Cellular Spheroids,” In Vitro, 19(6), pp. 479–488. [CrossRef] [PubMed]
Chang, R., and Sun, W., 2009, Biofabrication of Three-dimensional Liver Cell-embedded Tissue Constructs for In Vitro Drug Metabolism Models, LAP Lambert Academic Publishing, OmniScriptum GmbH & Co. KG Heinrich-Böcking-Straβe 6–8, Saarbrüken, Germany.
Sun, W., Darling, A., Starly, B., and Nam, J., 2004, “Computer Engineering: Overview, Scope and Challenges,” Biotechnol. Appl. Biochem., 39(1), pp. 29–47. [CrossRef] [PubMed]
Sun, W., and Lal, P., 2002, “Recent Development on Computer Aided Tissue Engineering—A Review,” Comput. Methods Programs Biomed., 67(2), pp. 85–103. [CrossRef] [PubMed]
Guijt, R. M., and Breadmore, M. C., 2008, “Maskless Photolithography Using UV LEDs,” Lab Chip, 8(8), pp. 1402–1404. [CrossRef] [PubMed]
Hamid, Q., Snyder, J., Wang, C., Timmer, M., Hammer, J., Guceri, S., and Sun, W., 2011, “Fabrication of Three-dimensional Scaffolds Using Precision Extrusion Deposition With an Assisted Cooling Device,” Biofabrication, 3(3), p. 034109. [CrossRef] [PubMed]
Shor, L., Guceri, S., Chang, R., Gordon, J., Kang, Q., Hartsock, L., An, Y. H., and Sun, W., 2009, “Precision Extruding Deposition (PED) Fabrication of Polycaprolactone (PCL) Scaffolds for Bone Tissue Engineering,” Biofabrication, 1(1), p. 015003. [CrossRef] [PubMed]
Yan, K. C., Nair, K., and Sun, W., 2010, “Three Dimensional Multi-scale Modeling and Analysis of Cell Damage in Cell-encapsulated Alginate Constructs,” J. Biomech., 43(6), pp. 1031–1038. [CrossRef] [PubMed]
Botchwey, E. A., Dupree, M. A., Pollack, S. R., Levine, E. M., and Laurencin, C. T., 2003, “Tissue Engineered Bone: Measurement of Nutrient Transport in Three-dimensional Matrices,” J. Biomed. Mater. Res. Part A, 67(1), pp. 357–367. [CrossRef]
Leong, K., Cheah, C., and Chua, C., 2003, “Solid Freeform Fabrication of Three-dimensional Scaffolds for Engineering Replacement Tissues and Organs,” Biomaterials, 24(13), pp. 2363–2378. [CrossRef] [PubMed]
Nair, K., Gandhi, M., Khalil, S., Yan, K. C., Marcolongo, M., Barbee, K., and Sun, W., 2009, “Characterization of Cell Viability During Bioprinting Processes,” Biotechnol. J., 4(8), pp. 1168–1177. [CrossRef] [PubMed]


Grahic Jump Location
Fig. 1

Applications of the dynamic DMM system

Grahic Jump Location
Fig. 2

(a) An image of the DMM with its major components labeled. (b) An image of the multinozzle biologics deposition system with its major components labeled. (c) A schematic of light projected onto the DMM's digital mirror. The schematic shows the division of the light source to project the pattern. The light for the projected pattern is labeled as “desired projection” and the unwanted light is labeled as “undesired projections.” (d) A schematic of the PDMS base and lid with their respective major components labeled. (e) A macroscopic image of the SU-8 microchannels fabricated into the PDMS base/platform. (f) An image illustrating the nozzle of the multinozzle biologics deposition system printing cells into the chip's microchannel.

Grahic Jump Location
Fig. 3

14 day cell proliferation study of treated and untreated open and closed microfluidic chips

Grahic Jump Location
Fig. 4

(a) A fluorescence image, taken at 14 days after cells were seeded into the microfluidic chip showing live cell stained green and dead cells stained red. (b) A confocal image, taken 24 h after cells were seeded into the microfluidic chips showing the nuclei (stain bright green) and the cytoplasm (stain green) of the cells in the channel. (c) An SEM image, showing an in-depth view of the cell morphology within the channels. (Figures are printed in black and white. See online for color.)

Grahic Jump Location
Fig. 5

The effects of conventional and cell printing seeding methods on cell proliferation within the microfluidic chips

Grahic Jump Location
Fig. 6

(a) A schematic of the microchannels on the microfluidic chips. (b) An image of the left side of the microchannels on the microfluidic chip showing the cells (labeled with the arrows) within the channel and channel's uniformity. (c) An image of the center of the microchannels on the microfluidic chip showing the cells (labeled with the arrows) within the channel and channel's uniformity. (d) An image of the right side of the microchannels on the microfluidic chip showing the cells (labeled with the arrows) within the channel and channel's uniformity.



Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In