Annals of Biomedical Engineering, Vol. 38, No. 1, January 2010 (Ó 2009) pp. 21–32 DOI: 10.1007/s10439-009-9831-x Print-and-Peel Fabrication for Microfluidics: What’s in it for Biomedical Applications? MARLON S. THOMAS,BRENT MILLARE,JOSEPH M. CLIFT,DUODUO BAO,CONNIE HONG, and VALENTINE I. VULLEV Department of Bioengineering, University of California, Riverside, CA 92521, USA (Received 30 May 2009; accepted 23 October 2009; published online 7 November 2009) Abstract—This article reviews the development and the important areas such as biosensing, diagnostics and advances of print-and-peel (PAP) microfabrication. PAP drug discovery.10,22,29,56,62,83,87 The huge attraction techniques provide means for facile and expedient prototyp- toward microfluidics results from its capabilities to ing of microfluidic devices. Therefore, PAP has the potential for broadening the microfluidics technology by bringing it to achieve significant reduction in reagent volumes, in researchers who lack regular or any accesses to specialized performance time and in power consumption while fabrication facilities and equipment. Microfluidics have, allowing massive parallelism.62,67,69,70 Over the last indeed, proven to be an indispensable toolkit for biological two decades, microfluidic systems have been developed and biomedical research and development. Through acces- for a broad range of application in biology, chemistry sibility to such methodologies for relatively fast and easy 2,5,8,15,40,51,55,59,61,65,68,73,77,81 prototyping, PAP has the potential to considerably accelerate and physics. the impacts of microfluidics on the biological sciences and Due to its availability and to the relative simplicity of engineering. In summary, PAP encompasses: (1) direct its molding, polydimethylsiloxane (PDMS) has become printing of the masters for casting polymer device compo- one of the preferred materials for fabrication of micro- nents; and (2) adding three-dimensional elements onto the fluidic devices.21,36,49,52,54,57,66 The masters for molding masters for single-molding-step formation of channels and cavities within the bulk of the polymer slabs. Comparative the PDMS components of the devices encompass the discussions of the different PAP techniques, along with the microchannel patterns as positive relief features on the current challenges and approaches for addressing them, smooth surfaces.23,28,81,86 The fabrication of such mas- outline the perspectives for PAP and how it can be readily ters involves a series of lithographic and etching adopted by a broad range of scientists and engineers. steps,7,9,24,60 most of which require a clean-room envi- ronment (with long-wavelength lighting) and specialized Keywords—PAP, LaserJet, Solid-ink, Wax, Printer, Litho- equipment. As an alternative, nonlithographic, or print- graphy, Biosensors, Poly(dimethylsiloxane), PDMS, l-TAS. and-peel (PAP), procedures allow for facile and expe- dient fabrication of masters for molding polymer com- ponents for microfluidic devices.6,31,33,35,45,76 ABBREVIATIONS The PAP fabrication techniques allow for direct printing of the masters, using regular office equipment 3D Three-dimensional 6,31,33,35,45,76 CAD Computer-aided design (Scheme 1). Any printing process that lTAS Micro-total-analytical systems deposits ink or toner on the surface of smooth and non-absorptive substrate leaves positive-relief printout PAP Print-and-peel 11,26,32,33,35,43,85 PDMS Poly(dimethylsiloxane) features. Therefore, LaserJet or solid- ink prints on overhead transparency films have proven their utility for PAP fabrication of masters for micro- 6,31,33,35,45,76 INTRODUCTION fluidic devices. Inkjet (bubble jet) printing offers another alternative Microfluidics has gained significance as an inter- for PAP. Via a ‘‘regular’’ printing process, however, disciplinary technology with applications in many the ink for bubble jet printers, when deposited, is absorbed by the substrates and does not leave relief features that exceed the roughness of the printed sur- Address correspondence to Valentine I. Vullev, Department of Bioengineering, University of California, Riverside, CA 92521, USA. faces. Modifying the inkjet printing process and Electronic mail: [email protected] allowing the controlled formation of micrometer-size 21 0090-6964/10/0100-0021/0 Ó 2009 The Author(s). This article is published with open access at Springerlink.com 22 THOMAS et al. relief features,47,85 on the other hand, can prove ben- by far the most targeted application for PAP-fabri- eficial for PAP. Martin et al.47 demonstrated the fab- cated microfluidic devices.6,19,20,26,27,32,35,72 Employing rication of 120-lm wide hydrophobic barriers on a nonlithographically fabricated microdevices for capil- chip by depositing polymer-containing droplets via lary gel electrophoretic separation of polynucleotide inkjet printing. Xia and Friend85 demonstrated pat- mixtures and achieving separation efficiencies exceed- terning of submicrometer-high relief features on poly- ing 2 9 105 theoretical plates per meter,89 presents an mer surfaces via controlled deposition of organic excellent proof for the feasibility of pursuing PAP for solvent with an inkjet printer. development of microfluidic devices for clinical diag- An addition of three-dimensional (3D) elements to nosis and biomedical research. the masters allows for a single-step molding of device Mixing of microflows is another key application for components with increased complexity76: i.e., a net- which PAP-fabricated devices have demonstrated their work of channels on multiple planes can be readily feasibility.43,45,48,76 Due to the laminar nature of mi- introduced to such device components and molded in a croflows (resultant from the prevalent viscous forces at single step (Scheme 1c–e).3,46,74,75 Furthermore, relatively low Reynolds numbers), achieving efficient molding the microfluidic components with 3D ele- mixing, faster than the inherent diffusion times, pre- ments, such as inlet and outlet connecting channels, sents a set of design and fabrication challenges for eliminates the need for drilling through the cured microfluidic devices.71 PAP allows a facile and expe- polymer.33,76 Drilling through PDMS not only pro- dient preparation of masters with relatively complex duces channels with considerably rough walls, but also features and transferring of these features in the places a risk of cracking the cured polymer slab. polymer device components via a single molding step. Due to its simplicity, expedience, and cost efficiency, Therefore, as an alternative to multiple fabrication and PAP techniques offer significant advantages for fast and alignment steps, required for lithographic fabrication facile prototyping of microfluidic devices.6,31,76 Although of micromixers, PAP offers venues for relatively simple PAP is less than a decade old, the recently developed PAP incorporation of passive mixers in microfluidic procedures for fabrication of biosensor,76 microelec- devices.45,48,76 trodes,33 devices for capillary electrophoresis,6,35,72 and Microfluidic generators of concentration gradients, lateral-gradient chemotaxis bioanalyzers31 demonstrate utilizing the laminar nature of the microflows, are the feasibility of this fabrication approach for microflu- promising tools for cell-biology and biomedical appli- idic biological applications. PAP, indeed, offers capabil- cations.25,84 Utilization of microfluidic gradient gen- ities for bringing microfluidics technology to researchers, erators for stem-cell17 and cancer research64 presents for whom access to specialized microfabrication facilities examples for the potential impact of such devices on is not readily available. biomedical science and engineering. PAP, indeed, Herein, we review the advances in PAP and their allows for facile and expedient fabrication of such implication for microfluidics. Discussions of the limi- microfluidic concentration-gradient generators.31,80 tations of PAP, along with approaches for addressing Micro-total-analytical systems (lTAS) have an these limitations, introduce possible venues for immense potential for positive impact on clinical expansion of these fabrication techniques. diagnosis, and on point-of-care research and develop- ment.30,34,58,82 The challenging fabrication of highly integrated lTAS devices, however, has impeded the WHAT’S IN IT FOR BIOMEDICAL realization of their full potential for health care and APPLICATIONS? applied bioengineering. The simplicity and the expe- diency that PAP offers for prototyping of microfluidic Microfluidics provides a set of indispensable tools devices, allow for bringing the lTAS research and for cell biology, biochemistry, neuroscience, bioanaly- development closer to the biomedical field. Utilizing sis, drug testing, biomechanics and other areas of PAP, medical teams (lacking extensive engineering biology and biomedical engineering.22,51,54,81 Micro- expertise) can be directly involved in the development fluidics, therefore, provides a liaison for integration of of lTAS devices targeted for specific clinical needs. engineering and biology. PAP allows for facile and While the lTAS high level of integration may prove expedient fabrication of microfluidic devices. Because challenging for personnel lacking microfabrication it does not require specialized facilities and equipment, expertise even if PAP is employed, a modular approach PAP has the immense potential for broadening the for building microfluidic devices presents an alterna- impact of microfluidics as a driving force for innova- tive.63 The current PAP technology