Review pubs.acs.org/ac
Recent Advances in Analytical Chemistry by 3D Printing Bethany Gross, Sarah Y. Lockwood, and Dana M. Spence*
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Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States
CONTENTS
Traditional Fabrication Techniques Benefits of 3D Printing 3D Printing Techniques and Applications Stereolithography Technology Applications Selective Laser Sintering Technology Applications Inkjet and Polyjet Printing Technology Applications Fused Deposition Modeling Technology Applications Laminated Object Manufacturing Technology Applications Direct Printing Metal Printers Wire-Feed Additive Manufacturing Applications Bioprinters Technology Applications Automation Selecting a Printer Conclusions and Future Directions Author Information Corresponding Author ORCID Author Contributions Notes Biographies References
direct printing (metal and bioprinting) technologies. In academic laboratories, 3D printing is now commonly viewed as a means to obtain a final product, as opposed to an exclusively prototyping tool. For these reasons, 3D printing has emerged as a popular fabrication tool for a variety of disciplines.5 This popularity is evidenced in the diversity of recent articles where 3D printing has found application, including electrochemical,6 tissue engineering,7 biological,8 microfluidics and lab-on-a-chip,9,10 medicine,11 custom labware,12 and environmental studies.13 With decreased printer and material costs, 3D printers are becoming commonplace in analytical laboratories where they are being utilized in a wide array of applications. This review highlights 3D printing techniques and applications in analytical and biochemical science, with an emphasis on research emerging in the last 2 years. Traditional Fabrication Techniques. An overarching theme emerges when surveying analytical chemistry literature; 3D printed devices are replacing thermoplastic and PDMSbased microfluidic devices. Additive manufacturing offers a clear-cut path toward recognizing the promise of achieving a true lab-on-a-chip, which has remained elusive thus far. 3D printing enables complex microfluidic device geometries, with an increasing material pool, not available when employing traditional fabrication techniques such as micromachining, hot embossing, injection molding, direct machining, soft lithography, and micromilling. Micromachining requires the use of a chemical etchant resulting in an intensive fabrication process, as well as less control over the final geometries.14 Hot embossing is a cost-effective technique based on replica molding and transference of microchannel features to a thermoplastic substrate from a master template under pressure and temperatures above the glass transition temperature (Tg) of the chosen substrate material.15 Hot embossing techniques or nanoimprint lithography have been used to fabricate nanostructures; however, this technique does not lend itself to multimaterial use as varying Tg would result in different viscosities during molding and deformities or curvature of the stamped substrate.16 Injection molding first requires the fabrication of a master with inverse features for structure transfer to a desired substrate during molding. A mold containing the master is sealed and injected with the chosen material. As with other high volume replication techniques, multiple thermoplastic polymer devices can be fabricated from a single master.17 Direct machining/writing of microfluidic devices utilizing laser microprocessing allows for sub-micrometer 3D structures to be formed without the use of a mask
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here have been numerous reviews that focus on the use of microfluidic devices prepared with such materials as polydimethylsiloxane (PDMS), thermoplastics, and glass using soft lithography, hot embossing, micromilling, and injection molding fabrication techniques.1−4 The additive manufacturing or 3-dimensional (3D) printing process provides many advantages compared to the aforementioned techniques, including one-step production of complex multimaterial designs, decreased fabrication time, the ability to integrate a variety of components, and an ever increasing material pool. 3D printing encompasses stereolithography (SLA), selective laser sintering (SLS), inkjet and polyjet printing, fused deposition modeling (FDM), laminated object manufacturing (LOM), and © 2016 American Chemical Society
Special Issue: Fundamental and Applied Reviews in Analytical Chemistry 2017 Published: November 14, 2016 57
DOI: 10.1021/acs.analchem.6b04344 Anal. Chem. 2017, 89, 57−70
Analytical Chemistry
Review
Figure 1. (A) Schematics of the bath (top left) and layer (top right) configurations for the SLA 3D printer technique. In the bath configuration, a moving platform lowers layer by layer into the vat of photocurable polymer, with polymerization occurring on the surface. In the layer configuration, polymerization occurs through a transparent window on the bottom of the vat with the moving platform rising out of the liquid as the product is built layer by layer. Reproduced with permission from Gross, B. C.; Erkal, J. L.; Lockwood, S. Y.; Chen, C.; Spence, D. M. Analytical Chemistry 2014, 86, 3240−3253 (ref 5). Copyright 2014, American Chemical Society. (B) In the 2PP method, the polymerization event occurs within the volume of polymer (right), in contrast to the one photon polymerization that occurs at the surface of the photoresin (left) as in traditional SLA techniques. Reprinted with permission from Journal of Photochemistry and Photobiology, 181, Wu, S.; Serbin, J.; Gu, M. Two-photon polymerization for threedimensional microfabrication, 1−11 (ref 53). Copyright 2006 with permission from Elsevier.
often required with micromachining.18,19 Soft lithography is a replica molding technique employing photo- or thermally curable elastomers, such as PDMS.20 This technique has found widespread use in the academic community, but the fabrication process can span a full day, devices are often nonreusable, and high aspect ratio features are difficult to maintain. Micromilling features a rotating cutting tool that subtracts material away from the bulk substrate (commonly plastics and metals), often using computer aided design (CAD) models for increased precision and control of the fabrication process. Feature resolution down to tens of micrometers is possible with micromilling.21 While the throughput of 3D printing is lacking in comparison to some of these techniques, one of the main improvements that 3D printing provides is that unique objects can be printed in succession with identical ones, without having to change out molds or fabricate a new master. In this manner, the cost of customization is negated when employing 3D printing technologies. As 3D printing finds increased use outside of initial prototyping, advances in material diversity and strength, print resolution, and print speed demonstrate 3D printing can be competitive with conventional fabrication and prototyping methods. Benefits of 3D Printing. One of the main applications of 3D printing is in biomedical sciences. Thermoplastic and PDMS based devices requiring manually intensive fabrication processes have not found the same level of utility in industrial
laboratories as in academic laboratories. Cost-effective paper based devices have allowed for biomedical devices to be implemented in under resourced areas; however, as fluidic movement is based on wicking action, there are limitations regarding fluid control on this platform and cell manipulation is prohibitive. While 3D printing may not have the same throughput as the aforementioned traditional fabrication techniques, printed devices are more amenable to integration of necessary components as well as standardization due to the nature of the fabrication process. Currently, the number of publications describing the use of 3D printing in the field of microfluidics alone is experiencing exponential growth.22 Furthermore, surface modification of printed devices is possible using conventional techniques such as UV-activation, reactive ion beams, and plasma oxidation due to common thermoplastics being included in the material pool for 3D printing.23,24 Efforts in researching biocompatible materials that can be printed are underway in many laboratories. A recent publication outlines the printing of 24-well plates using three types of printers and materials. Specifically, multijet modeling (MJM; polymer, VisiJet Crystal EX200; printer, HD3500+ 3D Systems), SLA (polymer, Watershed 11122XC and Fotosec SLA 7150 Clear; printer, Viper Pro, 3D Systems), and FDM (polymer, ABSplus P-430; printer, DesignJet) were employed for this task. The toxicity of the 3D printed polymer plates was evaluated using a zebrafish embryo test. Survival rates of the 58
DOI: 10.1021/acs.analchem.6b04344 Anal. Chem. 2017, 89, 57−70
Analytical Chemistry
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Direct laser writing, although similar to SLA with regard to orientation and concept, involves a developing step to remove excess resin and therefore ultimately is a subtractive manufacturing method.41 In constrained surface configuration,39,42 i.e., bat configuration or layer configuration, orientation of the building platform is reversed to allow for polymerization to occur at the bottom of the resin reservoir through a transparent window (Figure 1A). Therefore, after complete polymerization of a layer, the building platform rises slightly, allowing liquid resin to fill the void and the process repeats.6 Constrained surface configuration is especially beneficial if the photocurable resin is expensive or only a small quantity is available. Also, in contrast to free surface configuration, the height of the final product is not limited by the orientation of the building platform in the constrained surface configuration. Curing times of the final product are faster in this configuration due to a decrease in oxygen inhibition as a result of the location of polymerization.43 However, traditionally constrained surface configuration involves a separation step immediately after every curing event, in which the cured material is removed from the transparent window, typically coated in PDMS to assist in removal. As a result, fragile features can potentially be deformed, develop stress fractures, and the process is often time-consuming. Alternatively, continuous printing, a recent advancement, has simultaneously eliminated the need for a separation step, while significantly decreasing the print time by developing an oxygen permeable transparent window.44 The light source in constrained surface configuration is also reversed, with the source underneath the vat. The UV or LED lasers may again be employed for polymerization; however, a more efficient digital mirror device (DMD), i.e., digital light projection, is utilized in this orientation to crosslink an entire layer simultaneously. Initial DMD devices consisted of a costly crystal display (LCD);45 however, recent innovations in using digital micromirror displays have resulted in the development of cost-effective models.46 The build resolution in context of the DMD light source is determined by the projected pixel size.9 While the free surface configuration has additional post fabrication cleaning processes, both configurations require additional post fabrication UV exposure to strengthen the final product.47,48 An additional SLA technique that can achieve sub-micrometer resolutions (
