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Research Papers

Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices

[+] Author and Article Information
Yunus Alapan

Mem. ASME
Biomanufacturing and
Microfabrication Laboratory,
Mechanical and Aerospace
Engineering Department,
Case Western Reserve University,
Cleveland, OH 44106
e-mail: yxa81@case.edu

Muhammad Noman Hasan

Mem. ASME
Biomanufacturing and
Microfabrication Laboratory,
Mechanical and Aerospace
Engineering Department,
Case Western Reserve University,
Cleveland, OH 44106
e-mail: mnh38@case.edu

Richang Shen

Biomanufacturing and
Microfabrication Laboratory,
Mechanical and Aerospace
Engineering Department,
Case Western Reserve University,
Cleveland, OH 44106
e-mail: rxs580@case.edu

Umut A. Gurkan

Mem. ASME
Biomanufacturing and
Microfabrication Laboratory,
Mechanical and Aerospace
Engineering Department,
Biomedical Engineering Department,
Orthopedics Department,
Case Western Reserve University,
Cleveland, OH 44106;
Advanced Platform Technology Center,
Louis Stokes Cleveland Veterans
Affairs Medical Center,
Cleveland, OH 44106
e-mail: Umut@case.edu

1Y. Alapan and M. N. Hasan contributed equally to this work.

2Corresponding author.

Manuscript received March 31, 2015; final manuscript received July 30, 2015; published online September 29, 2015. Assoc. Editor: Ibrahim Ozbolat.

J. Nanotechnol. Eng. Med 6(2), 021007 (Sep 29, 2015) (9 pages) Paper No: NANO-15-1023; doi: 10.1115/1.4031231 History: Received March 31, 2015; Revised July 30, 2015

Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing.

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Figures

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Fig. 1

Hybrid manufacturing of a microfluidic platform using 3D printing and laser micromachining. (a) The microfluidic system is produced with a multiple layer lamination approach, by assembling; (1) a 3D printed top part encompassing inlets, outlets, and embedded manifolds for flow distribution, (2) a laser micromachined layer defining channel geometry, and (3) a glass substrate. Scale bar represents 10 mm length. The 3D printed top design includes; (i) inlets and outlets with 2 mm diameter, (ii) two manifolds of 50.8 mm length × 3 mm width × 1 mm height, and (iii) eight channel inlets and outlets with 1 mm diameter. (b) CAD design of the assembled 3D printed microfluidic device showing device inlet and outlet. Scale bar represents 10 mm length. (c) 3D printed microfluidic device is composed of eight parallel microchannels for processing of flow distributed from embedded manifolds.

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Fig. 2

Fabrication process of the 3D printed microfluidic device. (a) Multiple nozzle dispenses structural and supporting filler materials in the forward stroke. (b) Dispensed material is cured with UV light in the return stroke. (c) After the completion of printing, microfluidic device accompanies filler support materials before the postprocessing. (d) Final product after postprocessing is shown without the filler material. (e) Open ends of the 3D printed manifold were sealed after washing out the supporting filler material. (f) Complete assembly of the microfluidic device is achieved with inlet and outlet tubing connections.

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Fig. 3

Fabrication of the microfluidic device using 3D printing. The microfluidic devices fabricated with PolyJet printing are compared to the CAD design for performance evaluation. (a) PolyJet printing allowed fabrication of transparent microfluidic devices, while closely matching to the CAD design for (i and ii) inlet and outlet with clear flow pathways. (iii and iv) Moreover, edges of the base layer were clear and sharp as in the CAD design. Scale bars represent 10 mm length. (b) Surface evaluation of printed device in comparison to CAD design. (i and ii) Bottom layer of the 3D printed microfluidic device provided a smooth surface finishing.

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Fig. 4

3D printed microfluidic device provides uniform geometry in every microchannel. Microfluidic channel (a) height, and (b) width were uniform between every microchannel, with 250 μm ± 4.9 μm height and 3.75 mm ± 0.01 mm width. Error bars represent the standard deviation of the mean.

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Fig. 5

CFD Analysis of the designed microfluidic device. (a) Grid distribution showing hexahedral mesh for the channel array and tetrahedral mesh for the rest of the rest of the domain. (b) Pressure and (c) velocity distribution for the domain showed uniform flow characteristics between microchannels. (i and ii) Velocity distribution at the manifolds and microchannel inlet and outlets.

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Fig. 6

Velocity profile and flow distribution in the microfluidic channel. (a) Velocity profile along the height of the channel. (b) Velocity profile along the width of the channel. (c) Surface plot of velocity distribution at the channel at a plane 10 μm above the bottom surface. (d) Surface plot of velocity distribution at the channel at a plane 125 μm above the bottom surface. (e) Velocity in the channel along ss′ at different height of the channel.

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Fig. 7

Homogenous flow distribution in microchannels of the 3D printed microfluidic device. (a) 3D printed microfluidic device prototype. Scale bar represents 10 mm length. (b) Fluorescent and (c) phase contrast images of microfluidic channels injected with fluorescent microbeads delineating microchannels. (d)–(f) Flow velocity in microchannels are determined by seeding (d) fluorescent microbeads of 10 μm diameter. Sequential images of flowing microbeads were recorded using an inverted fluorescent microscope and a charge coupled device (CCD) camera. (e) Bead velocities are calculated by dividing the total displacement of an individual bead to the elapsed time. (f) Microbead velocities are determined for each microchannels at 50 μl/min and 100 μl/min flow rates supplied to the device. There was no statistically significant difference between microbead velocities in different microchannels at the same flow rates. Microbead velocities were significantly higher in all microchannels at 100 μl/min flow rate compared to 50 μl/min flow rate. The horizontal lines between individual groups represent statistically significant difference based on one way ANOVA test with Tukey's posthoc test for multiple comparisons (n = 8, p < 0.05). Error bars represent the standard deviation of the mean.

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Fig. 8

Capture of CD4+ T cells from blood using a hybrid manufactured microfluidic device. (a) and (b) Blood sample is injected into the 3D printed microfluidic device through the inlet port and the inlet manifold. (c) Injected blood sample was uniformly distributed to all channels through the integrated manifold. (d) and (e) CD4+ T cells were successfully captured from the processed blood sample. (d) Bright field image of all captured cells from blood is shown. White arrows indicate captured cells. (e) Captured cells were labeled with a CD4 antibody conjugated fluorescent label to validate the specific capture of the targeted CD4+ T cells.

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