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Self-powered infusion microfluidic pump for ex vivo drug delivery

Abstract

In this work, we present a new iSIMPLE concept (infusion Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation), which requires no external power for activation nor liquid manipulation, it is easy to use while its fabrication method is extremely simple, inexpensive and suited for mass replication. The pump consists of a working liquid, which is - after finger activation - absorbed in a porous material (e.g. filter paper). The air expelled from the porous material increases the pressure in the downstream outlet channel and propels the outlet liquid (i.e. the sample) through the channel or ejects it. Here we investigated the influence of different filter papers on the iSIMPLE flow rates, achieving a wide range from 30 down to 0.07 μL/min. We also demonstrated the versatility of the iSIMPLE in terms of the liquid volume that can be manipulated (from 0.5 μL up to 150 μL) and the working pressure reaching 64 kPa, unprecedented high for a self-powered microfluidics pump. In addition, using a 34 G microneedle mounted on the iSIMPLE, we successfully injected liquids with different viscosities (from 0.93 up to 55.88 cP) both into an agarose matrix and a skin-like biological ex vivo substrate (i.e. chicken breast tissue). This work validated the compatibility of the iSIMPLE with drug delivery in a controlled way into a skin-like matrix, envisioning a whole new scenario for intradermal injections using self-contained skin patch. In addition, due to the extreme flexibility of the design and manufacturing, the iSIMPLE concept offers enormous opportunities for completely autonomous, portable and cost effective LOC devices.

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References

  • J.B. Alarcon, A.W. Hartley, N.G. Harvey, J.A. Mikszta, Clin. Vaccine Immunol. 14, 375 (2007)

    Article  Google Scholar 

  • ALERE DETERMINE™ HIV-1/2 AG/AB COMBO (2016) https://www.alere.com/en/home/product-details/determine-1-2-ag-ab-combo.html?c=AU. Accessed 22 May 2018

  • P. Anton, Viscosity measurement of whole. Blood (2016)

  • A. Arora, I. Hakim, J. Baxter, R. Rathnasingham, R. Srinivasan, D.A. Fletcher, S. Mitragotri, Proc. Natl. Acad. Sci. U. S. A. 104, 4255 (2007)

    Article  Google Scholar 

  • S. Begolo, D.V. Zhukov, D.A. Selck, L. Li, R.F. Ismagilov, Lab Chip 14, 4616 (2014)

    Article  Google Scholar 

  • A.J. Chung, Y.S. Huh, D. Erickson, Biomed. Microdevices 11, 861 (2009)

    Article  Google Scholar 

  • Clearblue (2016) Clearblue pregnancy test. http://www.clearblue.com/healthcareprofessionals/pregnancy-tests. Accessed 22 May 2018

  • Clearview (2016) ALERE™ MALARIA AG P.F. https://www.alere.com/en/home/product-details/alere-malaria-ag-pf.html. Accessed 22 May 2018

  • G. Comina, A. Suska, D. Filippini, Biosens. Bioelectron. 77, 1153 (2015a)

    Article  Google Scholar 

  • G. Comina, A. Suska, D. Filippini, Angew. Chem. Int. Ed. Engl. 54, 8708 (2015b)

    Article  Google Scholar 

  • V.F. Curto, S. Coyle, R. Byrne, N. Angelov, D. Diamond, F. Benito-Lopez, Sensors Actuators B Chem. 175, 263 (2012a)

    Article  Google Scholar 

  • V.F. Curto, C. Fay, S. Coyle, R. Byrne, C.O.’. Toole, C. Barry, S. Hughes, N. Moyna, D. Diamond, F. Benito-Lopez, Sensors Actuators B Chem. 171, 1327 (2012b)

    Article  Google Scholar 

  • F. Dal Dosso, D. Decrop, E. Pérez-Ruiz, D. Daems, H. Agten, O. Al-Ghezi, O. Bollen, J. Breukers, F. De Rop, M. Katsafadou, J. Lepoudre, L. Lyu, P. Piron, R. Saesen, S. Sels, R. Soenen, E. Staljanssens, J. Taraporewalla, T. Kokalj, D. Spasic, J. Lammertyn, Anal. Chim. Acta (2017)

  • L.A. Dick, Innovative drug delivery technology to meet evolving need of biologics and small. Molecules (2015)

  • I.K. Dimov, L. Basabe-Desmonts, J.L. Garcia-Cordero, B.M. Ross, A.J. Ricco, L.P. Lee, Y. Park, A.J. Ricco, L.P. Lee, Lab Chip 11, 845 (2011)

    Article  Google Scholar 

  • E. Elizalde, R. Urteaga, C.L.A. Berli, Lab Chip 15, 2173 (2015)

    Article  Google Scholar 

  • J. Etter, C. Ng, A. Bohlke, S. Burton, and L. Dick, (n.d.)

  • C.P. Foley, N. Nishimura, K.B. Neeves, C.B. Schaffer, W.L. Olbricht, Biomed. Microdevices 11, 915 (2009)

    Article  Google Scholar 

  • E.L. França, E.B. Ribeiro, E.F. Scherer, D.G. Cantarini, R.S. Pessôa, F.L. França, A.C. Honorio-França, Biomed Res. Int 840379 (2014)

  • N. Fries, Capillary Transport Processes in Porous Materials: Experiment and Model, University of Bremen, (2010)

  • E. Fu, T. Liang, P. Spicar-Mihalic, J. Houghtaling, S. Ramachandran, P. Yager, Anal. Chem. 84, 4574 (2012)

    Article  Google Scholar 

  • H. Gensler, R. Sheybani, P.-Y. Li, R. Lo Mann, E. Meng, Biomed. Microdevices 14, 483 (2012)

    Article  Google Scholar 

  • L. Gervais, E. Delamarche, Lab Chip 9, 3330 (2009)

    Article  Google Scholar 

  • D. G. Greene, P. Wuthrich, R. C. Portilla, M. Herring, R. P. Mahoney, S. Webb, J. Sorvillo, and D. S. Soane, in 13th Annu. PEGS Summit (Boston, 2017)

  • W. Guo, J. Hansson, W. van der Wijngaart, Langmuir 32, 12650 (2016)

    Article  Google Scholar 

  • J. Gupta, S.S. Park, B. Bondy, E.I. Felner, M.R. Prausnitz, Biomaterials 32, 6823 (2011)

    Article  Google Scholar 

  • U.O. Häfeli, A. Mokhtari, D. Liepmann, B. Stoeber, Biomed. Microdevices 11, 943 (2009)

    Article  Google Scholar 

  • K. Hosokawa, K. Sato, N. Ichikawa, M. Maeda, Lab Chip 4, 181 (2004)

    Article  Google Scholar 

  • Inkscape (2016) https://inkscape.org/en/about/overview/. Accessed 22 May 2018

  • B.A. Inman, W. Etienne, R. Rubin, R.A. Owusu, T.R. Oliveira, D.B. Rodriques, P.F. Maccarini, P.R. Stauffer, A. Mashal, M.W. Dewhirst, Int. J. Hyperth. 29, 206 (2013)

    Article  Google Scholar 

  • N. Inoue, E. Takai, T. Arakawa, K. Shiraki, Mol. Pharm. 11, 1889 (2014)

    Article  Google Scholar 

  • W.W. Koelmans, G. Krishnamoorthy, A. Heskamp, J. Wissink, S. Misra, N. Tas, Mech. Eng. Res. 3, 51 (2013)

    Article  Google Scholar 

  • T. Kokalj, Y. Park, M. Vencelj, M. Jenko, L.P. Lee, Lab Chip 14, 4329 (2014)

    Article  Google Scholar 

  • E. Leonard, in Subcutaneous and Intramuscular Injections. Administration of Medication via intradermal (2017)

    Google Scholar 

  • Po-Ying Li, J. Shih, R. Lo, B. Adams, R. Agrawa, S. Saati, M. S. Humayun, Yu-Chong Tai, and E. Meng, in 2007 IEEE 20th Int. Conf. Micro Electro Mech. Syst. (IEEE, 2007), pp. 15–18

  • G. Li, Y. Luo, Q. Chen, L. Liao, J. Zhao, Biomicrofluidics 6, 14118 (2012)

    Article  Google Scholar 

  • D.Y. Liang, A.M. Tentori, I.K. Dimov, L.P. Lee, Biomicrofluidics 5, 24108 (2011)

    Article  Google Scholar 

  • R. Lo, P.-Y. Li, S. Saati, R.N. Agrawal, M.S. Humayun, E. Meng, Biomed. Microdevices 11, 959 (2009)

    Article  Google Scholar 

  • D. Mark, S. Haeberle, G. Roth, F. von Stetten, R. Zengerle, Chem. Soc. Rev. 39, 1153 (2010)

    Article  Google Scholar 

  • W. Martanto, J.S. Moore, O. Kashlan, R. Kamath, P.M. Wang, J.M. O’Neal, M.R. Prausnitz, Pharm. Res. 23, 104 (2006)

    Article  Google Scholar 

  • A.W. Martinez, S.T. Phillips, G.M. Whitesides, E. Carrilho, Anal. Chem. 82, 3 (2010)

    Article  Google Scholar 

  • N.-T. Nguyen, S.A.M. Shaegh, N. Kashaninejad, D.-T. Phan, Adv. Drug Deliv. Rev. 65, 1403 (2013)

    Article  Google Scholar 

  • A. Nisar, N. Afzulpurkar, B. Mahaisavariya, A. Tuantranont, Sensors Actuators B Chem. 130, 917 (2008)

    Article  Google Scholar 

  • P. Novo, V. Chu, J.P. Conde, Biosens. Bioelectron. 57, 284 (2014)

    Article  Google Scholar 

  • M. Ochoa, C. Mousoulis, B. Ziaie, Adv. Drug Deliv. Rev. 64, 1603 (2012)

    Article  Google Scholar 

  • K.W. Oh, C.H. Ahn, J. Micromech. Microeng. 16, 13 (2006)

    Article  Google Scholar 

  • S.-J. Paik, S. Byun, J.-M. Lim, Y. Park, A. Lee, S. Chung, J. Chang, K. Chun, Sensors Actuators A 114, 276 (2004)

    Article  Google Scholar 

  • S.L. Perry, J.J.L. Higdon, P.J.A. Kenis, Lab Chip 10, 3112 (2010)

    Article  Google Scholar 

  • F.N. Pirmoradi, J.K. Jackson, H.M. Burt, M. Chiao, Lab Chip 11, 3072 (2011)

    Article  Google Scholar 

  • L. Qin, O. Vermesh, Q. Shi, J.R. Heath, Lab Chip 9 (2016, 2009)

  • X. Qiu, J.A. Thompson, Z. Chen, C. Liu, D. Chen, S. Ramprasad, M.G. Mauk, S. Ongagna, C. Barber, W.R. Abrams, D. Malamud, P.L.A.M. Corstjens, H.H. Bau, Biomed. Microdevices 11, 1175 (2009)

    Article  Google Scholar 

  • Quidel (2016) QuickVue Influenza A+B. https://www.quidel.com/immunoassays/rapid-influenza-tests/quickvue-influenza-test. Accessed 22 May 2018

  • R. Riahi, A. Tamayol, S.A.M. Shaegh, A.M. Ghaemmaghami, M.R. Dokmeci, A. Khademhosseini, Curr. Opin. Chem. Eng. 7, 101 (2015)

    Article  Google Scholar 

  • P. Ruef, J. Gehm, L. Gehm, C. Felbinger, J. Pöschl, N. Kuss, Gen. Physiol. Biophys. 33, 285 (2014)

    Article  Google Scholar 

  • R.K. Sivamani, B. Stoeber, G.C. Wu, H. Zhai, D. Liepmann, H. Maibach, Skin Res. Technol. 11, 152 (2005)

    Article  Google Scholar 

  • X. Wang, J.A. Hagen, I. Papautsky, Biomicrofluidics 7, 14107 (2013)

    Article  Google Scholar 

  • S.P. Woods, T.G. Constandinou, J. Micro-Bio Robot. 11, 19 (2016)

    Article  Google Scholar 

  • S. Yadav, S.J. Shire, D.S. Kalonia, J. Pharm. Sci. 99, 4812 (2010)

    Article  Google Scholar 

  • W. Yang, Y.G. Nam, B.-K. Lee, K. Han, T.H. Kwon, D.S. Kim, Jpn. J. Appl. Phys. 49, 06GM01 (2010)

    Google Scholar 

  • E.-C. Yeh, C.-C. Fu, L. Hu, R. Thakur, J. Feng, L.P. Lee, Sci. Adv. 3, e1501645 (2017)

    Article  Google Scholar 

  • P.K. Yuen, V.N. Goral, Lab Chip 10, 384 (2010)

    Article  Google Scholar 

  • D. Zhang, D.B. Das, C.D. Rielly, J. Pharm. Sci. 103, 613 (2014)

    Article  Google Scholar 

  • M. Zimmermann, H. Schmid, P. Hunziker, E. Delamarche, Lab Chip 7, 119 (2007)

    Article  Google Scholar 

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Acknowledgments

The research leading to these results has received funding from the Research Foundation - Flanders (FWO G086114 N), and the KU Leuven (OT 13/058, C3 project C32/17/007, C2 project C24/16/022).

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Correspondence to Jeroen Lammertyn.

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Dal Dosso, F., Kokalj, T., Belotserkovsky, J. et al. Self-powered infusion microfluidic pump for ex vivo drug delivery. Biomed Microdevices 20, 44 (2018). https://doi.org/10.1007/s10544-018-0289-1

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  • DOI: https://doi.org/10.1007/s10544-018-0289-1

Keywords

  • Passive pump
  • Disposable pump
  • Infusion pump
  • Self-powered microfluidics
  • Lab-on-a-chip
  • Drug delivery