MICROFLUIDIC DEVICE FOR MICROPARTICLE FABRICATION

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MICROFLUIDIC DEVICE FOR MICROPARTICLE FABRICATION Aldo Y. Tenorio-Barajas1, Ma. de la Luz Olvera1,2, Claudia Mendoza-Barrera3, Víctor Altuzar3 1Programa de Doctorado en Nanociencias y Nanotecnología, CINVESTAV-IPN, México D.F. 07360, México, 2Departamento de Ingeniería Eléctrica-Sección de Electrónica del Estado Sólido, CINVESTAV-IPN, México D.F. 07360, México, 3Facultad de Ciencias Físico-Matemáticas, Benemérita Universidad Autónoma de Puebla, Puebla Pue., 72570, México. INTRODUCTION SET UP AND SYNTHESIS The microfluidic field is an emerging area of research interest, particularly for processing new biomaterials with medical applications; among these we found microcapsules, nanocarriers and drug delivery nanoparticles for pharmaceutical use. Here, we present the design and fabrication of microfluidic chips on (Polydimethylsiloxane) PDMS and glass in order to synthesize and to homogenize biopolymeric microcapsules. We present the soft photolithographic process, etching, bonding as well the port creation. We drive chitosan polymer solution trough channels for microparticle fabrication and encapsulation by using a homemade four-channel pump [1]. Characterization of size and morphology of microparticles were achieved through optical microscopy and DLS, respectively. left image shows a microfluidic chip engraved in glass, center microfluidic channels with resin as mask, right image a connector, holder and pipe SOFT PHOTOLITOGRAPHY A) Through lithography the pattern is transferred to a substrate of Si or Glass with a photosensitive resin, B) A laser beam transfers the pattern of the channels C) this leads a protuberance of the channels in resin D) pouring PDMS above the pattern replicates the channels E) After being cured, PDMS solidifies leading channels F) This channels can be covered with Glass or PDMS after a treatment with plasma oxygen leading an irreversible union. After microfluidic chip fabrication, fitting and connections where designed and fabricated with CNC in order to obtain a good sealing and fluid conduction avoiding leaking. One important issue on microfluidics is the injection system, this was achieved with a 4 channel microinjection home-made pump system previously reported [1]. The image shows the general diagram of connection. The next step was the determination of liquid flow regime to obtain a continuous drop formation and continuous jet: image A and B. Once the reactants are used, this leads the formation of microspheres that serves as carriers or microreactors encapsulating the desire cargo content A similar process is used to obtain the channels in glass, covering the substrate with chrome A), transferring the pattern B), then removing the unnecessary parts C), this masks the glass and allows etching on the glass with buffered HF mixture, this engraves the channels directly onto glass surface D), after engraving the glass the chrome is removed and a cover is mounted to seal the channels with another glass and thermal bonding or with PDMS and plasma oxygen E). Finally the channels are obtained. Several patterns were tested and the etching process depends on concentration and time of immersion of chip inside etchant, we obtain a etch rate of 1µm/min similar to those reported by Marten [2] for glass chips. When PDMS is used, the pattern is transferred by contact with the resin. this is removed with photoresin revealer, also the concentration and time of exposure are crucial to obtain a good aspect ratio and smooth surface. we achieve an aspect ratio of nearly 90% table 1, obtained with micrometer, the depth was obtained with profilometer with consistent thickness of ~2 µm when photoresin was used and 200 µm of thickness for chrome mask obtained by CVD process. DIAGRAM OF CONECTION 100 µm A 100 µm B Right image shows the formation of microparticles of chitosan through the use of the chip shown in the image above A, in drop formation regime. This image shows a regular and homogenous size and shape of microspheres, of about 10 µm in diameter with flow regimes of 6 µl/min fort external carrier flow and 3 µl/min for the injection velocity of both reagents QN and TPP, varying the concentrations from 1% to 0.25 %. Further characterization is needed to complement this results such as DLS and TEM. Image right shows the Raman spectra of precursors of chitosan microparticles, TPP and Chitosan characteristic peaks of TTP and QN. 2885, 1654, 1591, 936, and 896cm -1 for QN; and 1160, 1136, 1093, 1027, 1009, 989, 944,736, 534, and 489cm-1 for TPP. Draw width to physical channel width (µm) Aspect ratio (%) 5.0-4.7 94 3.0-2.7 90 2.0-1.8 1.0-0.9 CONCLUSIONS: We create a microfluidic injection system and produced micro channels in Glass and Glass/PDMS. We achieved the creation of microspheres of chitosan which could lead the formation of carriers for a cargo transport such as protein or drug, this project is under development and the data shown here are preliminary results, more characterizations and studies are needed in order to corroborate and compare the data obtained, studies of degradation and as well as morphology, size and shape are in progress. [1] A. Y. Tenorio-Barajas, M. R. Matus-Muñoz, M. L. Olvera, V. Altuzar and C. Mendoza-Barrera, "Automatization and control of home-made micro injection pumps for a microfluidic system," 2016 13th International Conference on Electrical Engineering, Computing Science and Automatic Control (CCE), Mexico City, 2016, pp. 1-4. [2] Stjernstrom, M. and J. Roeraade (1998). "Method for fabrication of microfluidic systems in glass." Journal of Micromechanics and Microengineering 8(1): 33-38.