Microfluidics: a review

Borut Pečar, Drago Resnik, Matej Možek, Danilo Vrtačnik

Abstract


Microfluidics technologies have become a powerful tool in life science research laboratories over the past three decades. This review discusses three important segments of the field from origins and current status to future prospective: a) materials and microfabrication technologies from the field, b) research and development of essential microfluidic components and c) integration of components into complex microfluidic systems that will, according to some forecasts, play a key role in improving the quality of life for future generations. The most sophisticated microfluidic systems developed by now are Point-of-Care systems, that  are based on Lab-on-Chip technologies. As these subfields are very extensive and go beyond the scope of this review, some carefully chosen additional review papers are provided.

Keywords


microfluidics; materials; technologies; micropumps; flowmeters; microneedles; fuel steam reformers; microdosing systems; LOC; POC

Full Text:

PDF

References


Lai, S., Wang, S., Luo, J., Lee, L. J., Yang, S. T., & Madou, M. J. (2004). Design of a compact disk-like microfluidic platform for enzyme-linked immuno-sorbent assay. Analytical chemistry, 76(7), 1832-1837, https://doi.org/10.1021/ac0348322 .

Dittrich, P. S., & Manz, A. (2006). Lab-on-a-chip: microfluidics in drug discovery. Nature reviews Drug discovery, 5(3), 210-218, https://doi.org/10.1038/nrd1985 .

Nguyen, N. T., Wereley, S. T., & Shaegh, S. A. M. (2019). Fundamentals and applications of microflu-idics. Artech house, https://doi.org/10.1108/info.2002.4.2.49.1 .

Lai, S., Wang, S., Luo, J., Lee, L. J., Yang, S. T., & Madou, M. J. (2004). Design of a compact disk-like microfluidic platform for enzyme-linked immuno-sorbent assay. Analytical chemistry, 76(7), 1832-1837, https://doi.org/10.1021/ac0348322 .

Streets, A. M., & Huang, Y. (2013). Chip in a lab: Microfluidics for next generation life science re-search. Biomicrofluidics, 7(1), 011302, https://doi.org/10.1063/1.4789751 .

Lei, K. F. (2014). Materials and fabrication techniques for nano-and microfluidic devices, https://doi.org/10.1039/9781849737609-00001 .

Wolf, M. P., Salieb-Beugelaar, G. B., & Hunziker, P. (2018). PDMS with designer functionalities—Properties, modifications strategies, and applica-tions. Progress in Polymer Science, 83, 97-134, https://doi.org/10.1016/j.progpolymsci.2018.06.001 .

Elwenspoek, M., & Jansen, H. V. (2004). Silicon micromachining (Vol. 7). Cambridge University Press, https://doi.org/10.1007/978-3-662-04321-9_3 .

Resnik, D., Aljančič, U., Vrtačnik, D., Cvar, M., & Amon, S. (1998). Mikroobdelava silici-ja. Vakuumist, 1(let 18), 4-11

Vrtačnik D et al. RIE of deep silicon microchannels for microfluidic applications. Proceedings, 44th In-ternational Conference MIDEM, September 2008

Tilli, M., Paulasto-Kröckel, M., Petzold, M., Theuss, H., Motooka, T., & Lindroos, V. (Eds.). (2020). Handbook of silicon based MEMS materials and technologies. Elsevier, https://doi.org/10.1016/b978-0-12-817786-0.00062-1 .

Owen, K. J., VanDerElzen, B., Peterson, R. L., & Najafi, K. (2012, January). High aspect ratio deep silicon etching. In 2012 IEEE 25th International Conference on Micro Electro Mechanical Systems (MEMS) (pp. 251-254). IEEE, https://doi.org/10.1109/memsys.2012.6170138 .

Giang, U. B. T., Lee, D., King, M. R., & DeLouise, L. A. (2007). Microfabrication of cavities in polydi-methylsiloxane using DRIE silicon molds. Lab on a Chip, 7(12), 1660-1662, https://doi.org/10.1039/b714742b .

Chen, K. S., Ayón, A. A., Zhang, X., & Spearing, S. M. (2002). Effect of process parameters on the surface morphology and mechanical performance of silicon structures after deep reactive ion etching (DRIE). Journal of Microelectromechanical Systems, 11(3), 264-275, https://doi.org/10.1109/jmems.2002.1007405 .

Vrtačnik D et al. Optimization of DRIE silicon microstructures with Bosch process. Proceedings, 47th International Conference MIDEM, septem-ber 2011.

Li, X., Abe, T., Liu, Y., & Esashi, M. (2002). Fabrica-tion of high-density electrical feed-throughs by deep-reactive-ion etching of Pyrex glass. Journal of Microelectromechanical Systems, 11(6), 625-630, https://doi.org/10.1109/jmems.2002.805211 .

Stjernström, M., & Roeraade, J. (1998). Method for fabrication of microfluidic systems in glass. Journal of Micromechanics and Microengine-ering, 8(1), 33, https://doi.org/10.1088/0960-1317/8/1/006 .

Iliescu, C. (2006). Microfluidics in glass: technolo-gies and applications. Informacije MIDEM, 36(4), 204, http://www.dlib.si/details/URN:NBN:SI:doc-U408KBPW.

Xia, Y., & Whitesides, G. M. (1998). Soft lithograp-hy. Annual review of materials science, 28(1), 153-184, https://doi.org/10.1146/annurev.matsci.28.1.153 .

Goral, V. N., Hsieh, Y. C., Petzold, O. N., Faris, R. A., & Yuen, P. K. (2010). Hot embossing of plastic microfluidic devices using poly (dimethylsiloxane) molds. Journal of Micromechanics and Microengine-ering, 21(1), 017002, https://doi.org/10.1088/0960-1317/21/1/017002 .

Matteucci, M., Christiansen, T. L., Tanzi, S., Østergaard, P. F., Larsen, S. T., & Taboryski, R. (2013). Fabrication and characterization of injec-tion molded multi level nano and microfluidic systems. Microelectronic engineering, 111, 294-298, https://doi.org/10.1016/j.mee.2013.01.060 .

Sethu, P., & Mastrangelo, C. H. (2004). Cast epoxy-based microfluidic systems and their appli-cation in biotechnology. Sensors and Actuators B: Chemical, 98(2-3), 337-346,

https://doi.org/10.1016/j.snb.2003.09.036 .

Shiu, P. P., Knopf, G. K., Ostojic, M., & Nikumb, S. (2008). Rapid fabrication of tooling for microflui-dic devices via laser micromachining and hot embossing. Journal of Micromechanics and Micro-engineering, 18(2), 025012, https://doi.org/10.1088/0960-1317/18/2/025012 .

Ali, M. Y. (2009). Fabrication of microfluidic chan-nel using micro end milling and micro electrical discharge milling. International Journal of Mechani-cal and Materials Engineering, 4(1), 93-97, https://doi.org/10.1115/1.802946.paper44 .

Thompson, K., Gianchandani, Y. B., Booske, J., & Cooper, R. F. (2002). Direct silicon-silicon bonding by electromagnetic induction heating. Journal of Microelectromechanical Systems, 11(4), 285-292, https://doi.org/10.1109/jmems.2002.800929 .

Takagi, H., Maeda, R., Chung, T. R., & Suga, T. (1998). Low-temperature direct bonding of silicon and silicon dioxide by the surface activation met-hod. Sensors and Actuators A: Physical, 70(1-2), 164-170, https://doi.org/10.1016/s0924-4247(98)00128-9 .

Quenzer, H. J., & Benecke, W. (1992). Low-temperature silicon wafer bonding. Sensors and Actuators A: Physical, 32(1-3), 340-344, https://doi.org/10.1016/0924-4247(92)80009-r .

Resnik, D., Vrtačnik, D., Aljančič, U., & Amon, S. (2000). Study of low-temperature direct bonding of (111) and (100) silicon wafers under various am-bient and surface conditions. Sensors and Actua-tors A: Physical, 80(1), 68-76, https://doi.org/10.1016/s0924-4247(99)00299-x .

Resnik, D., Vrtacnik, D., Aljancic, U., & Amon, S. (2000). Direct bonding of (111) and (100) oriented silicon wafers. Informacije MIDEM, 30(1), 20-31, https://doi.org/10.1016/s0924-4247(99)00299-x .

Xiao, Z. X., Wu, G. Y., Li, Z. H., Zhang, G. B., Hao, Y. L., & Wang, Y. Y. (1999). Silicon–glass wafer bonding with silicon hydrophilic fusion bonding technology. Sensors and Actuators A: Physi-cal, 72(1), 46-48, https://doi.org/10.1016/s0924-4247(98)00197-6 .

Resnik, D., Aljančič, U., Vrtačnik, D., Možek, M., Pečar, B., & Amon, S. (2012, March). Microfluidic platforms realized by micromachining and anodic bonding of Si and glass substrates. In 2012 8th In-ternational Caribbean Conference on Devices, Circuits and Systems (ICCDCS) (pp. 1-4). IEEE, https://doi.org/10.1109/iccdcs.2012.6188939 .

Resnik, D., Možek, M., Dolžan, T., Amon, S., & Vrtačnik, D. (2012). Spajanje podlag silicij-steklo z anodnim bondiranjem. Vakuumist, 3(32), 4-11.

Tsao, C. W. (2016). Polymer microfluidics: Simple, low-cost fabrication process bridging academic lab research to commercialized produc-tion. Micromachines, 7(12), 225, https://doi.org/10.3390/mi7120225 .

Suzuki, Y., Yamada, M., & Seki, M. (2010). Sol–gel based fabrication of hybrid microfluidic devices composed of PDMS and thermoplastic substrates. Sensors and Actuators B: Chemical, 148(1), 323- 329, https://doi.org/10.1016/j.snb.2010.04.018 .

Tsao, C. W., & DeVoe, D. L. (2009). Bonding of thermoplastic polymer microfluidics. Microfluidics and Nanofluidics, 6(1), 1-16, https://doi.org/10.1007/s10404-008-0361-x .

Lee, K. S., & Ram, R. J. (2009). Plastic–PDMS bon-ding for high pressure hydrolytically stable active microfluidics. Lab on a Chip, 9(11), 1618-1624, https://doi.org/10.1039/b820924c .

Pečar, B., Možek, M., & Vrtačnik, D. (2017). Ther-moplastic-PDMS polymer covalent bonding for microfluidic applications. Informacije MIDEM, 47(3), 147-154.

Conde, J. P., Madaboosi, N., Soares, R. R., Fernan-des, J. T. S., Novo, P., Moulas, G., & Chu, V. (2016). Lab-on-chip systems for integrated bioa-nalyses. Essays in biochemistry, 60(1), 121-131, https://doi.org/10.1042/ebc20150013 .

Krutzsch, W. C., & Cooper, P. (1986). Introduction: classification and selection of pumps. Pump Handbook.

Van Lintel, H. T. G., Van de Pol, F. C. M., & Bouwstra, S. (1988). A piezoelectric micropump based on micromachining of silicon. Sensors and actuators, 15(2), 153-167, https://doi.org/10.1016/0250-6874(88)87005-7 .

Carrozza, M. C., Croce, N., Magnani, B., & Dario, P. (1995). A piezoelectric-driven stereolithography-fabricated micropump. Journal of Micromechanics and Microengineering, 5(2), 177, https://doi.org/10.1088/0960-1317/5/2/032 .

Koch, M., Harris, N., Evans, A. G., White, N. M., & Brunnschweiler, A. (1998). A novel micromachined pump based on thick-film piezoelectric actuati-on. Sensors and Actuators A: Physical, 70(1-2), 98-103, https://doi.org/10.1016/s0924-4247(98)00120-4 .

Pečar, B., Možek, M. & Vrtačnik, D. Piezoelektrična mikročrpalka z ventiloma, ki posnemata delovanje bioloških venskih zaklopk : patent SI 25227 (A), 2017-12-29. Ljubljana: Urad RS za intelektualno lastnino, 2017

Ardito, R., Bertarelli, E., Corigliano, A., & Gafforelli, G. (2013). On the application of piezolaminated composites to diaphragm micropumps. Composite Structures, 99, 231-240, https://doi.org/10.1016/j.compstruct.2012.11.041 .

Pečar, B. et al. (2017). Microcylinder pump employing 0.57 Pb (Sc1/2Nb1/2) O3–0.43 PbTiO3 piezoelectric actuator. Journal of Optoelectronics and Advanced Materials, 19(September-October 2017), 617-622.

Pečar, B. et al. Silicon piezoelectric vaveless mic-ropumps. V: JUNKAR, Mihael (ur.), et al. MIT & SLIM 2011 : proceedings of the 11th International Conference on Management of Innovative Techno-logies & 2nd International Conferen

Jin, Z. J., Gao, Z. X., Chen, M. R., & Qian, J. Y. (2018). Parametric study on Tesla valve with re-verse flow for hydrogen decompressi-on. International Journal of Hydrogen Ener-gy, 43(18), 8888-8896, https://doi.org/10.1016/j.ijhydene.2018.03.014 .

Huang, P. H., Nama, N., Mao, Z., Li, P., Rufo, J., Chen, Y., ... & Huang, T. J. (2014). A reliable and programmable acoustofluidic pump powered by oscillating sharp-edge structures. Lab on a Chip, 14(22), 4319-4323, https://doi.org/10.1039/c4lc00806e .

Tanyeri, M., & Tay, S. (2018). Viable cell culture in PDMS-based microfluidic devices. In Methods in cell biology (Vol. 148, pp. 3-33). Academic Press, https://doi.org/10.1016/bs.mcb.2018.09.007 .

Wang, C., Kim, J. S., & Park, J. (2017, June). Micro check valve integrated magnetically actuated micropump for implantable drug delivery. In 2017 19th International Conference on Solid-State Sen-sors, Actuators and Microsystems (TRANSDUCERS) (pp. 1711-1713). IEEE, https://doi.org/10.1109/transducers.2017.7994396 .

Gadad, N., Shivayyanavar, N., Viannie, L. R., Jaya-chandra, S. Y., Banapurmath, N. R., Shettar, A. S., ... & Kaulgud, V. (2018). Fabrication and develop-ment of magnetically actuated PDMS micropump for drug delivery. MS&E, 376(1), 012128, https://doi.org/10.1088/1757-899x/376/1/012128 .

Kawun, P., Leahy, S., & Lai, Y. (2016). A thin PDMS nozzle/diffuser micropump for biomedical applica-tions. Sensors and Actuators A: Physical, 249, 149-154, https://doi.org/10.1016/j.sna.2016.08.032 .

Chien, H. L., & Lee, Y. C. (2017). A ball valve mi-cro-pump based on axially symmetrical nozzle fab-ricated by excimer laser micromachining technol-ogy. International Journal of Precision Engineering and Manufacturing, 18(10), 1315-1320, https://doi.org/10.1007/s12541-017-0156-7 .

Ye, Y., Chen, J., Ren, Y. J., & Feng, Z. H. (2018). Valve improvement for high flow rate piezoelec-tric pump with PDMS film valves. Sensors and Ac-tuators A: Physical, 283, 245-253, https://doi.org/10.1016/j.sna.2018.09.064 .

Mashayek, A., Caulfield, C. P., & Peltier, W. R. (2017). Role of overturns in optimal mixing in stra-tified mixing layers. Journal of Fluid Mecha-nics, 826, 522-552, https://doi.org/10.1017/jfm.2017.374 .

Rusli, M. Q. A., Chee, P. S., Arsat, R., Lau, K. X., & Leow, P. L. (2018). Electromagnetic actuation du-al-chamber bidirectional flow micropump. Sensors and Actuators A: Physical, 282, 17-27, https://doi.org/10.1016/j.sna.2018.08.047 .

Ala'aldeen, T., Demming, S., Dietzel, A., & Büttgenbach, S. (2016). Design, fabrication, and characterization of a continuous flow micropump system. Journal of Thermal Science and Engineer-ing Applications, 8(2), 021006, https://doi.org/10.1115/1.4031922 .

Gidde, R. R., & Pawar, P. M. (2017). On effect of viscoelastic characteristics of polymers on perfor-mance of micropump. Advances in Mechanical En-gineering, 9(2), 1687814017691211, https://doi.org/10.1177/1687814017691211 .

Smits, J. G. (1990). Piezoelectric micropump with three valves working peristaltically. Sensors and Actuators A: Physical, 21(1-3), 203-206, https://doi.org/10.1016/0924-4247(90)85039-7 .

Berg, J. M., Anderson, R., Anaya, M., Lahlouh, B., Holtz, M., & Dallas, T. (2003). A two-stage discrete peristaltic micropump. Sensors and Actuators A: Physical, 104(1), 6-10, https://doi.org/10.1016/s0924-4247(02)00434-x .

Pečar, B., Križaj, D., Vrtačnik, D., Resnik, D., Dol-žan, T., & Možek, M. (2014). Piezoelectric peristal-tic micropump with a single actuator. Journal of Micromechanics and Microengineering, 24(10), 105010, https://doi.org/10.1088/0960-1317/24/10/105010 .

Davies, M. J., Johnston, I. D., Tan,C. K. L., & Tracey, M. C. (2010). Whole blood pumping with a micro-throttle pump. Biomicrofluidics, 4(4), 044112, https://doi.org/10.1063/1.3528327 .

Pečar, B., Vrtačnik, D., Resnik, D., Možek, M., Aljančič, U., Dolžan, T., ... & Križaj, D. (2013). A strip-type microthrottle pump: Modeling, design and fabrication. Sensors, 13(3), 3092-3108, https://doi.org/10.3390/s130303092 .

Dolžan, T., Pečar, B., Možek, M., Resnik, D., & Vrtačnik, D. (2015). Self-priming bubble tolerant microcylinder pump. Sensors and Actuators A: Physical, 233, 548-556, https://doi.org/10.1016/j.sna.2015.07.015 .

Gravesen, P., Branebjerg, J., & Jensen, O. S. (1993). Microfluidics-a review. Journal of microme-chanics and microengineering, 3(4), 168, https://doi.org/10.3390/s130303092 .

Wang, J., Sullivan, M., & Hua, S. Z. (2007). Electro-lytic-bubble-based flow sensor for microfluidic systems. Journal of microelectromechanical sys-tems, 16(5), 1087-1094, https://doi.org/10.1016/j.sna.2015.05.020 .

Nezhad, A. S., Ghanbari, M., Agudelo, C. G., Packirisamy, M., Bhat, R. B., & Geitmann, A. (2012). PDMS microcantilever-based flow sensor integration for lab-on-a-chip. IEEE Sensors jour-nal, 13(2), 601-609, https://doi.org/10.1109/jsen.2012.2223667 .

Amnache, A., Omri, M., & Fréchette, L. G. (2018). A silicon rectangular micro-orifice for gas flow measurement at moderate Reynolds numbers: design, fabrication and flow analyses. Microfluidics and Nanofluidics, 22(6), 58, https://doi.org/10.1007/s10404-018-2077-x .

Richter, A., Hofmann, K. A., Plettner, A., & Sand-maier, H. (1991, June). The electrohydrodynamic micro flow meter. In TRANSDUCERS'91: 1991 In-ternational Conference on Solid-State Sensors and Actuators. Digest of Technical Papers (pp. 935-938). IEEE, https://doi.org/10.1109/sensor.1991.149042 .

Accoto, D., Damiani, F., Campisi, M., Castrataro, P., Campolo, D., Guglielmelli, E., & Dario, P. (2006, January). A micro flow-meter for closed-loop management of biological samples. In 2005 IEEE Engineering in Medicine and Biology 27th An-nual Conference (pp. 5062-5065). IEEE, https://doi.org/10.1109/iembs.2005.1615614

Nie, C., Frijns, A. J. H., Mandamparambil, R., Zev-enbergen, M. A. G., & den Toonder, J. M. J. (2015). An evaporation based digital microflow meter. Journal of Micromechanics and Microengi-neering, 25(11), 115008, https://doi.org/10.1088/0960-1317/25/11/115008 .

Van Oudheusden, B. W. (1992). Silicon thermal flow sensors. Sensors and Actuators A: Physi-cal, 30(1-2), 5-26, https://doi.org/10.1016/0924-4247(92)80192-6 .

Petropoulos, A., & Kaltsas, G. (2010). Study and evaluation of a PCB-MEMS liquid microflow sen-sor. Sensors, 10(10), 8981-9001, https://doi.org/10.3390/s101008981 .

Yaghmourali, Y. V., Ahmadi, N., & Abbaspour-Sani, E. (2017). A thermal-calorimetric gas flow meter with improved isolating featu-re. Microsystem Technologies, 23(6), 1927-1936, https://doi.org/10.1007/s00542-016-2915-2 .

Ke, W., Liu, M., Li, T., & Wang, Y. (2019). MEMS thermal gas flow sensor with self-test func-tion. Journal of Micromechanics and Microengine-ering, 29(12), 125009, https://doi.org/10.1088/1361-6439/ab4aef .

Kang, W., Choi, H. M., & Choi, Y. M. (2018). Deve-lopment of MEMS-based thermal mass flow sen-sors for high sensitivity and wide flow rate ran-ge. Journal of Mechanical Science and Techno-logy, 32(9), 4237-4243, https://doi.org/10.1007/s12206-018-0822-4 .

Kaltsas, G., Petropoulos, A., Tsougeni, K., Pago-nis, D. N., Speliotis, T., Gogolides, E., & Nassi-opoulou, A. G. (2007, December). A novel micro-fabrication technology on organic substrates—Application to a thermal flow sensor. In J. Phys. Conf. Ser (Vol. 92, No. 1, p. 12046), https://doi.org/10.1088/1742-6596/92/1/012046 .

Li, Y., Baek, K., Gulari, M., Lin, D., & Wise, K. D. (2005, October). A vacuum-isolated thermal mi-croflowmeter for in-vivo drug delivery. In SENSORS, 2005 IEEE (pp. 4-pp). IEEE, https://doi.org/10.1109/icsens.2005.1597787 .

Liu, P., Zhu, R., & Que, R. (2009). A flexible flow sensor system and its characteristics for fluid mechanics measurements. Sensors, 9(12), 9533-9543, https://doi.org/10.3390/s91209533 .

Ahrens, R., & Schlote-Holubek, K. (2009). A micro flow sensor from a polymer for gases and liquids. Journal of Micromechanics and Microengi-neering, 19(7), 074006, https://doi.org/10.1088/0960-1317/19/7/074006 .

Li, C., Wu, P. M., Han, J., & Ahn, C. H. (2008). A flexible polymer tube lab-chip integrated with microsensors for smart microcatheter. Biomedical microdevices, 10(5), 671-679, https://doi.org/10.1007/s10544-008-9178-3 .

Kuo, J. T., Chang, L. Y., Li, P. Y., Hoang, T., & Meng, E. (2011). A microfluidic platform with in-tegrated flow sensing for focal chemical stimula-tion of cells and tissue. Sensors and Actuators B: Chemical, 152(2), 267-276, https://doi.org/10.1016/j.snb.2010.12.019 .

Pečar B et al. Microflowmeter for microfluidics applications. Conference proceedings, 52nd Inter-national Conference MIDEM, September 28 - 30 2016, 122-126.

Miralles, V., Huerre, A., Malloggi, F., & Jullien, M. C. (2013). A review of heating and temperature control in microfluidic systems: techniques and applications. Diagnostics, 3(1), 33-67, https://doi.org/10.3390/diagnostics3010033 .

Matsui, T., Franzke, J., Manz, A., & Janasek, D. (2007). Temperature gradient focusing in a PDMS/glass hybrid microfluidic chip. Electrophoresis, 28(24), 4606-4611, https://doi.org/10.1002/elps.200700272 .

Kempitiya, A., Borca-Tasciuc, D. A., Mohamed, H. S., & Hella, M. M. (2009). Localized microwave heating in microwells for parallel DNA amplifica-tion applications. Applied Physics Letters, 94(6), 064106, https://doi.org/10.1063/1.3078273 .

Mao, H., Yang, T., & Cremer, P. S. (2002). A micro-fluidic device with a linear temperature gradient for parallel and combinatorial mea-surements. Journal of the American Chemical Soci-ety, 124(16), 4432, https://doi.org/10.1021/ja017625x

Zhang, K., Jian, A., Zhang, X., Wang, Y., Li, Z., & Tam, H. Y. (2011). Laser-induced thermal bubbles for microfluidic applications. Lab on a Chip, 11(7), 1389-1395, https://doi.org/10.1039/c0lc00520g .

Guijt, R. M., Dodge, A., van Dedem, G. W., de Rooij, N. F., & Verpoorte, E. (2003). Chemical and physical processes for integrated temperature control in microfluidic devices. Lab on a Chip, 3(1), 1-4, https://doi.org/10.1039/b210629a .

Mavraki, E., Moschou, D., Kokkoris, G., Vourdas, N., Chatzandroulis, S., & Tserepi, A. (2011). A conti-nuous flow μPCR device with integrated microhe-aters on a flexible polyimide substrate. Procedia Engineering, 25, 1245-1248, https://doi.org/10.1016/j.proeng.2011.12.307 .

Selva, B., Marchalot, J., & Jullien, M. C. (2009). An optimized resistor pattern for temperature gradi-ent control in microfluidics. Journal of Micro-mechanics and Microengineering, 19(6), 065002, https://doi.org/10.1088/0960-1317/19/6/065002 .

Hsieh, T. M., Luo, C. H., Huang, F. C., Wang, J. H., Chien, L. J., & Lee, G. B. (2008). Enhancement of thermal uniformity for a microthermal cycler and its application for polymerase chain reaction, https://doi.org/10.1016/j.snb.2007.10.063 . Sensors and Actuators B: Chemical, 130(2), 848-856.

Resnik, D., Vrtačnik, D., Možek, M., Pečar, B., & Amon, S. (2011). Experimental study of heat-treated thin film Ti/Pt heater and temperature sensor properties on a Si microfluidic plat-form. Journal of Micromechanics and Microengine-ering, 21(2), 025025, https://doi.org/10.1088/0960-1317/21/2/025025 .

Larraneta, E., Lutton, R. E., Woolfson, A. D., & Donnelly, R. F. (2016). Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Materials Science and Engineering: R: Reports, 104, 1-32, https://doi.org/10.1016/j.mser.2016.03.001 .

Kim, Y. C., Park, J. H., & Prausnitz, M. R. (2012). Microneedles for drug and vaccine deli-very. Advanced drug delivery reviews, 64(14), 1547-1568, https://doi.org/10.1016/j.addr.2012.04.005 .

Smart, W. H., & Subramanian, K. (2000). The use of silicon microfabrication technology in pain-less blood glucose monitoring. Diabetes technology & therapeutics, 2(4), 549-559, https://doi.org/10.1089/15209150050501961 .

Gardeniers, H. J., Luttge, R., Berenschot, E. J., De Boer, M. J., Yeshurun, S. Y., Hefetz, M., ... & Van Den Berg, A. (2003). Silicon micromachined hol-low microneedles for transdermal liquid trans-port. Journal of Microelectromechanical systems, 12(6), 855-862, https://doi.org/10.1109/jmems.2003.820293 .

Chen, B., Wei, J., Tay, F. E., Wong, Y. T., & Iliescu, C. (2008). Silicon microneedle array with bio-degradable tips for transdermal drug deli-very. Microsystem Technologies, 14(7), 1015-1019, https://doi.org/10.1007/s00542-007-0530-y .

Lin, L., & Pisano, A. P. (1999). Silicon-processed microneedles. Journal of Microelectromechanical Systems, 8(1), 78-84, https://doi.org/10.1109/84.749406 .

Martanto, W., Moore, J. S., Couse, T., & Prausnitz, M. R. (2006). Mechanism of fluid infusion during microneedle insertion and retraction. Journal of Controlled Release, 112(3), 357-361, https://doi.org/10.1016/j.jconrel.2006.02.017 .

Doddaballapur, S. (2009). Microneedling with dermaroller. Journal of cutaneous and aesthetic surgery, 2(2), 110,

https://doi.org/10.4103/0974-2077.58529.

Wei-Ze, L., Mei-Rong, H., Jian-Ping, Z., Yong-Qiang, Z., Bao-Hua, H., Ting, L., & Yong, Z. (2010). Super-short solid silicon microneedles for trans-dermal drug delivery applications. International jo-urnal of pharmaceutics, 389(1-2), 122-129, https://doi.org/10.1016/j.ijpharm.2010.01.024 .

Teo, M. A. L., Shearwood, C., Ng, K. C., Lu, J., & Moochhala, S. (2005). In vitro and in vivo characte-rization of MEMS microneedles. Biomedical micro-devices, 7(1), 47-52, https://doi.org/10.1007/s10544-005-6171-y .

Davis, S. P., Martanto, W., Allen, M. G., & Pra-usnitz, M. R. (2005). Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Transac-tions on Biomedical Engineering, 52(5), 909-915, https://doi.org/10.1109/tbme.2005.845240 .

Park, J. H., Allen, M. G., & Prausnitz, M. R. (2006). Polymer microneedles for controlled-release drug delivery. Pharmaceutical research, 23(5), 1008-1019, https://doi.org/10.1007/s11095-006-0028-9 .

Bariya, S. H., Gohel, M. C., Mehta, T. A., & Sharma, O. P. (2012). Microneedles: an emerging trans-dermal drug delivery system. Journal of Pharmacy and Pharmacology, 64(1), 11-29, https://doi.org/10.1111/j.2042-7158.2011.01369.x .

Karande, P., Jain, A., & Mitragotri, S. (2006). Rela-tionships between skin's electrical impedance and permeability in the presence of chemical enhan-cers. Journal of Controlled Release, 110(2), 307-313, https://doi.org/10.1016/j.jconrel.2005.10.012 .

Prausnitz, M. R., & Langer, R. (2008). Transdermal drug delivery. Nature biotechnology, 26(11), 1261-1268, https://doi.org/10.1038/nbt.1504 .

Resnik, D., Možek, M., Pečar, B., Dolžan, T., Janež, A., Urbančič, V., & Vrtačnik, D. (2015). Characteri-zation of skin penetration efficacy by Au-coated Si microneedle array electrode. Sensors and Actua-tors A: Physical, 232, 299-309, https://doi.org/10.1016/j.sna.2015.05.020 .

Deng, Y., Chen, J., Zhao, Y., Yan, X., Zhang, L., Choy, K., & Tang, T. (2016). Transdermal delivery of siRNA through microneedle array. Scientific re-ports, 6, 21422, https://doi.org/10.1038/srep21422 .

Kim, E., Erdos, G., Huang, S., Kenniston, T. W., Balmert, S. C., Carey, C. D. & Korkmaz, E. (2020). Microneedle array delivered recombinant corona-virus vaccines: Immunogenicity and rapid transla-tional development. EBioMedicine, 102743, https://doi.org/10.1016/j.ebiom.2020.102743 .

Resnik, D., Možek, M., Pečar, B., Janež, A., Urban-čič, V., Iliescu, C., & Vrtačnik, D. (2018). In vivo experimental study of noninvasive insulin micro-injection through hollow Si microneedle ar-ray. Micromachines, 9(1), 40, https://doi.org/10.3390/mi9010040 .

Iliescu, F. S., Teo, J. C. M., Vrtacnik, D., Taylor, H., & Iliescu, C. (2018). Cell therapy using an array of ultrathin hollow microneedles. Microsystem Technologies, 24(7), 2905-2912, https://doi.org/10.1007/s00542-017-3631-2 .

Li, Z., Khajepour, A., & Song, J. (2019). A compre-hensive review of the key technologies for pure electric vehicles. Energy, 182, 824-839, https://doi.org/10.1016/j.energy.2019.06.077

Tanaka, S., Chang, K. S., Min, K. B., Satoh, D., Yoshida, K., & Esashi, M. (2004). MEMS-based components of a miniature fuel cell/fuel reformer system. Chemical Engineering Journal, 101(1-3), 143-149,https://doi.org/10.1016/j.cej.2004.01.017.

Holladay, J. D., Jones, E. O., Dagle, R. A., Xia, G. G., Cao, C., & Wang, Y. (2004). High efficiency and low carbon monoxide micro-scale methanol pro-cessors. Journal of power sources, 131(1-2), 69-72, https://doi.org/10.1016/j.jpowsour.2004.01.003 .

Kawamura, Y., Ogura, N., Yamamoto, T., & Igaras-hi, A. (2006). A miniaturized methanol reformer with Si-based microreactor for a small PEMFC. Chemical Engineering Science, 61(4), 1092-1101, https://doi.org/10.1016/j.ces.2005.08.014 .

Hsueh, C. Y., Chu, H. S., Yan, W. M., & Chen, C. H. (2010). Transport phenomena and performance of a plate methanol steam micro-reformer with ser-pentine flow field design. Applied Energy, 87(10), 3137-3147, ps://doi.org/10.1016/j.apenergy.2010.02.027 .

Jeong, H., Kim, K. I., Kim, T. H., Ko, C. H., Park, H. C., & Song, I. K. (2006). Hydrogen production by steam reforming of methanol in a micro-channel reactor coated with Cu/ZnO/ZrO2/Al2O3 ca-talyst. Journal of power sources, 159(2), 1296-1299, https://doi.org/10.1016/j.energy.2019.06.077 .

Mei, D., Feng, Y., Qian, M., & Chen, Z. (2016). An innovative micro-channel catalyst support with a micro-porous surface for hydrogen production via methanol steam reforming. International Journal of Hydrogen Energy, 41(4), 2268-2277, https://doi.org/10.1016/j.ijhydene.2015.12.044 .

Huang, Y. X., Jang, J. Y., & Cheng, C. H. (2014). Fractal channel design in a micro methanol steam reformer. International journal of hydrogen ener-gy, 39(5), 1998-2007, https://doi.org/10.1016/j.ijhydene.2013.11.088 .

Sarafraz, M. M., Safaei, M. R., Goodarzi, M., & Arjomandi, M. (2019). Reforming of methanol with steam in a micro-reactor with Cu–SiO2 poro-us catalyst. International Journal of Hydrogen Energy, 44(36), 19628-19639, https://doi.org/10.1016/j.ijhydene.2019.05.215 .

Wang, H. S., Huang, K. Y., Huang, Y. J., Su, Y. C., & Tseng, F. G. (2015). A low-temperature partial-oxidation-methanol micro reformer with high fuel conversion rate and hydrogen production yi-eld. Applied Energy, 138, 21-30, https://doi.org/10.1016/j.apenergy.2014.10.033 .

Resnik, D., Hočevar, S., Batista, J., Vrtačnik, D., Možek, M., & Amon, S. (2012). Si based methanol catalytic micro combustor for integrated steam reformer applications. Sensors and Actuators A: Physical, 180, 127-136, https://doi.org/10.1016/j.sna.2012.04.029 .

Peruško, D., Možek, M., Pečar, B., Aljančič, U., Resnik, D., Vrtačnik, D., & Amon, S. (2011, May). Temperature control of methanol fuel microrea-ctor for hydrogen production. In 2011 Proceedings of the 34th International Convention MIPRO (pp. 141-144). IEEE, https://doi.org/10.1109/mipro.2014.6859540 .

Pečar, B., Možek, M., Resnik, D., Vrtačnik, D., Aljančič, U., Penič, S., & Amon, S. (2010, May). Microflow-generator for fuel-cell methanol hydro-gen microreactor. In The 33rd International Con-vention MIPRO (pp. 110-115). IEEE, https://doi.org/10.1109/mipro.2014.6859540 .

Tsai, N. C., & Sue, C. Y. (2007). Review of MEMS-based drug delivery and dosing systems. Sensors and Actuators A: Physical, 134(2), 555-564, https://doi.org/10.1016/j.sna.2006.06.014 .

Böhm, S., Timmer, B., Olthuis, W., & Bergveld, P. (2000). A closed-loop controlled electrochemi-cally actuated micro-dosing system. Journal of Micromechanics and Microengineering, 10(4), 498, https://doi.org/10.1088/0960-1317/10/4/303 .

Reynaerts, D., Peirs, J., & Van Brussel, H. (1997). An implantable drug-delivery system based on shape memory alloy micro-actuation. Sensors and Actuators A: Physical, 61(1-3), 455-462, https://doi.org/10.1016/s0924-4247(97)80305-6 .

Koerner, J., Helmlinger, M., & Schuerle, H. (2009). U.S. Patent No. 7,584,903. Washington, DC: U.S. Patent and Trademark Office.

Ianchulev, T., Weinreb, R., Tsai, J. C., Lin, S., & Pasquale, L. R. (2018). High-precision piezo-ejection Su, Y. C., & Lin, L. (2004). A water-powered micro drug delivery system. Journal of Microelectromechanical Systems, 13(1), 75-82, https://doi.org/10.1109/jmems.2003.823215 .

Than, A., Liu, C., Chang, H., Duong, P. K., Cheung, C. M. G., Xu, C., ... & Chen, P. (2018). Self-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug deli-very. Nature communications, 9(1), 1-12, https://doi.org/10.1038/s41467-018-06981-w .

Kabata, A., Suzuki, H., Kishigami, Y., & Haga, M. (2005). Micro system for injection of insulin and monitoring of glucose concentration. In SENSORS, 2005 IEEE (pp. 4-pp). IEEE, https://doi.org/10.1109/icsens.2005.1597663 .

Vrtačnik D et al. Micro-sized PDMS membranes in sealed microfluidic reservoirs. Conference proce-edings 2016. 52nd International Conference MIDEM, September 28 - 30 2016, Ankaran, Slove-nia.

Vrtačnik D et al.. Nosljiv integrirani mikrodozirni sistem s poljem silicijevih mikroigel za transdermalni vnos zdravil : patent SI24564 (A), 2015-06-30. Lju-bljana: Urad RS za intelektualno lastnino, 2015.

Lei, K. F. (2014). Materials and fabrication tech-niques for nano-and microfluidic devices, https://doi.org/10.1039/9781849737609-00001 .

Barbooti, M. (Ed.). (2015). Environmental applica-tions of instrumental chemical analysis. CRC press, https://doi.org/10.1201/b18376 .

»https://www.elveflow.com«. Accessed 16.11.2020.

Sengupta, J., & Hussain, C. M. (2019). Graphene and its derivatives for Analytical Lab on Chip plat-forms. TrAC Trends in Analytical Chemistry, 114, 326-337, https://doi.org/10.1016/j.trac.2019.03.015 .

Moser, I., Jobst, G., Aschauer, E., Svasek, P., Var-ahram, M., Urban, G. & Berezov, T. T. (1995). Min-iaturized thin film glutamate and glutamine bio-sensors. Biosensors and Bioelectronics, 10(6-7), 527-532, https://doi.org/10.1016/b978-1-85617-242-4.50137-3 .

Yoon, J. Y., & Kim, B. (2012). Lab-on-a-chip path-ogen sensors for food safety. Sensors, 12(8), 10713-10741, https://doi.org/10.3390/s120810713 .

Weigl, B. H., Bardell, R. L., & Cabrera, C. R. (2003). Lab-on-a-chip for drug development. Advanced drug delivery reviews, 55(3), 349-377, https://doi.org/10.1016/s0169-409x(02)00223-5 .

Ertl, P., Sticker, D., Charwat, V., Kasper, C., & Lep-perdinger, G. (2014). Lab-on-a-chip technologies for stem cell analysis. Trends in biotechnolo-gy, 32(5), 245-253, https://doi.org/10.1016/j.tibtech.2014.03.004 .

Pol, R., Céspedes, F., Gabriel, D., & Baeza, M. (2017). Microfluidic lab-on-a-chip platforms for en-vironmental monitoring. TrAC Trends in Analytical Chemistry, 95, 62-68, https://doi.org/10.1016/j.trac.2017.08.001 .

Wu, J., Dong, M., Santos, S., Rigatto, C., Liu, Y., & Lin, F. (2017). Lab-on-a-chip platforms for detec-tion of cardiovascular disease and cancer bi-omarkers. Sensors, 17(12), 2934, https://doi.org/10.3390/s17122934 .

Ai, Y., Zhang, F., Wang, C., Xie, R., & Liang, Q. (2019). Recent progress in lab-on-a-chip for phar-maceutical analysis and pharmacologi-cal/toxicological test. TrAC Trends in Analytical Chemistry, 117, 215-230, https://doi.org/10.1016/j.trac.2019.06.026 .

Jung, W., Han, J., Choi, J. W., & Ahn, C. H. (2015). Point-of-care testing (POCT) diagnostic systems using microfluidic lab-on-a-chip technolo-gies. Microelectronic Engineering, 132, 46-57, https://doi.org/10.1016/j.mee.2014.09.024 .

Sia, S. K., & Kricka, L. J. (2008). Microfluidics and point-of-care testing. Lab on a Chip, 8(12), 1982-1983, https://doi.org/10.1039/b817915h .

Nguyen, T., Zoëga Andreasen, S., Wolff, A., & Duong Bang, D. (2018). From lab on a chip to po-int of care devices: The role of open source micro-controllers. Micromachines, 9(8), 403, https://doi.org/10.3390/mi9080403 .

Sia, S. K., & Kricka, L. J. (2008). Microfluidics and point-of-care testing. Lab on a Chip, 8(12), 1982-1983, https://doi.org/10.1039/b817915h .

Park, S., Zhang, Y., Lin, S., Wang, T. H., & Yang, S. (2011). Advances in microfluidic PCR for point-of-care infectious disease diagnostics. Biotechnology advances, 29(6), 830-839, https://doi.org/10.1016/j.biotechadv.2011.06.017 .

Toley, B. J., Das, D., Ganar, K. A., Kaur, N., Meena, M., Rath, D., ... & Soni, S. (2018). Multidimensional Paper Networks: A New Generation of Low-Cost Pump-Free Microfluidic Devices. Journal of the In-dian Institute of Science, 98(2), 103-136, https://doi.org/10.1007/s41745-018-0077-1 .

Böhm, A., & Biesalski, M. (2017). based microflui-dic devices: A complex low-cost material in high-tech applications. MRS Bulletin, 42(5), 356,

https://doi.org/10.1557/mrs.2017.92.

Yetisen, A. K., Akram, M. S., & Lowe, C. R. (2013). Paper based microfluidic point-of-care diagnostic devices. Lab on a Chip, 13(12), 2210-2251, https://doi.org/10.1039/c3lc50169h .

Ahn, C. H., Choi, J. W., Beaucage, G., Nevin, J. H., Lee, J. B., Puntambekar, A., & Lee, J. Y. (2004). Disposable smart lab on a chip for point-of-care clinical diagnostics. Proceedings of the IEEE, 92(1), 154-173, https://doi.org/10.1109/jproc.2003.820548 .

Neuzil, P., Pipper, J., & Hsieh, T. M. (2006). Dis-posable real-time microPCR device: lab-on-a-chip at a low cost. Molecular bioSystems, 2(6-7), 292-298, https://doi.org/10.1039/b605957k .

Sun, S., Yang, M., Kostov, Y., & Rasooly, A. (2010). ELISA-LOC: lab-on-a-chip for enzyme-linked immunodetection. Lab on a Chip, 10(16), 2093-2100, https://doi.org/10.1039/c003994b .

Upaassana, V. T., Ghosh, S., Chakraborty, A., Birch, M. E., Joseph, P., Han, J., ... & Ahn, C. H. (2019). Highly sensitive Lab on a Chip (LOC) immunoas-say for early diagnosis of respiratory disease cau-sed by respirable crystalline silica (RCS). Analytical chemistry, 91(10), 6652-6660, https://doi.org/10.1021/acs.analchem.9b00582 .

Tripoliti, E. E., Karanasiou, G. S., Ioannidou, P., Toumpaniaris, P., Goletsis, Y., Baussels, J., ... & Leekens, B. (2018, July). KardiaTool: An Integrated POC Solution for Non-invasive Diagnosis and Therapy Monitoring of Heart Failure Patients. In 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Soci-ety (EMBC) (pp. 3878-3881). IEEE, https://doi.org/10.1109/embc.2018.8513298 .

Hou, X., Zhang, Y. S., Trujillo-de Santiago, G., Alvarez, M. M., Ribas, J., Jonas, S. J., ... & Khademhosseini, A. (2017). Interplay between materials and microfluidics. Nature Reviews Mate-rials, 2(5), 1-15, https://doi.org/10.1038/natrevmats.2017.28 .

Bohr, A., Colombo, S., & Jensen, H. (2019). Future of Microfluidics in Research and in the Market. In Microfluidics for Pharmaceutical Applications (pp. 425-465). William Andrew Publishing, https://doi.org/10.1016/b978-0-12-812659-2.00016-8 .

]Lo, R. C. (2017). Microfluidics technology: future prospects for molecular diagnostics. Advanced Health Care Technologies, 3, 3-17, https://doi.org/10.2147/ahct.s94024 .

Tian, W. C., & Finehout, E. (2008). Current and Future Trends in Microfluidics within Biotechno-logy Research. In Microfluidics for Biological Appli-cations (pp. 385-411). Springer, Boston, MA, https://doi.org/10.1007/978-0-387-09480-9_11 .




DOI: https://doi.org/10.33180/InfMIDEM2021.101

Refbacks

  • There are currently no refbacks.


Copyright (c) 2021 Borut Pečar, Drago Resnik, Matej Možek, Danilo Vrtačnik

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.