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Mikroakışkan Platformda Proteine Bağlı Üremik Toksin Adsorpsiyonunun Modellenmesi

Year 2021, Issue: 27, 354 - 361, 30.11.2021
https://doi.org/10.31590/ejosat.971386

Abstract

Bu çalışmada kronik böbrek hastalarının üremik toksisite sorununa çözüm bulmak amacıyla hemodiyaliz sistemine entegre edilebilecek bir mikroakışkan çipin geliştirilmesi hedeflenmiştir. Mikroakışkan çip içerisine Sol-Jel metodu ile Na-Y Zeolit ile fonksiyonelleştirilmiş TEOS-PEO hidrojeli yüklenerek, kanda bulunan ve proteine bağlı üremik toksinlerden biri olan İndoksil Sülfat (IS) toksininin, çip içerisinde adsorbe edilerek hastaların kanlarından uzaklaştırılması hipotezi test edilmiştir. Solid Works programı ile S-şekilli bir mikrokanal tasarlanarak, Comsol Multiphysics programında simülasyon çalışmaları gerçekleştirilmiştir. Simülasyon sonrasında taramalı elektron mikroskopisi (SEM) ve bilgisayarlı mikro-tomografi (mikro-CT) analizi ile karakterizasyonları gerçekleştirilen Na-Y Zeolit içerikli hidrojellerin hem kesikli deney koşullarında hem de geliştirilen mikroakışkan sistemde sürekli modda simüle kan sıvısı ile yapılan protein bağlı indoksil sülfat toksininin detoksifikasyonu incelenmiştir. Geliştirilen bu mikroakışkan tasarımın, klinikte kronik böbrek hastalarının kanında biriken proteine bağlı toksinlerin uzaklaştırılmasını sağlayabilecek yenilikçi yöntemler geliştirilmesine katkı sağlayacağı düşünülmektedir.

Supporting Institution

TÜBİTAK

Thanks

Bu çalışma “Proteine Bağlı Üremik Toksinlerin In Vitro Adsorpsiyonunun Mikroakışkan Platformda Modellemesi” başlıklı 2209/A projesi Tübitak tarafından desteklenmiştir.

References

  • Armignacco P., Garzotto F., Neri M., Lorenzin A., Ronco C. (2015). Wak engineering evolution. Blood Purification, 39(1-3), 110-114. Caravaca, F., Arrobas, M. ve Dominguez, C. (2000). Serum Albumin and Other Serum Protein Fractions in Stable Patients on Peritoneal Dialysis. Peritoneal Dialysis International, (20), 703–707.
  • Davenport, A. (2014). How can dialyzer designs improve solute clearances for hemodialysis patients?. Hemodialysis International, 18(1), 43–47.
  • Eyüpoğlu, C. (2020). Kronik Böbrek Hastalığının Erken Tanısı için Yeni Bir Klinik Karar Destek Sistemi. Avrupa Bilim ve Teknoloji Dergisi, 20, 448-455.
  • Floege, J., Granolleras, C., Deschodt, G., Heck, M., Baudin, G., Branger, B., Tournier, O., Reinhard, B., Eisenbach, G.M., Smeby, L.C., et al. (1989). High-flux synthetic versus cellulosic membranes for beta 2-microglobulin removal during hemodialysis, hemodiafiltration and hemofiltration. Nephrology Dialysis Transplantation, 4(7), 653-657.
  • Gura, V., Rivara, M. B., Bieber, S., Munshi, R., Smith, N. C., Linke, L., et al. (2016). A wearable artificial kidney for patients with end-stage renal disease. JCI Insight, 1(8), e86397.
  • Ikizler, T. A., Flakoll, P.J., Parker, R.A., Hakim, R.M. (1994) Amino Acid and Albumin Losses During Hemodialysis. Kidney Internationale, 46(3), 830–837.
  • Kaplan, A.A., Halley, S.E., Lapkin, R.A., Graeber, C.W. (1995) Dialysate Protein Losses with Bleach Processed Polysulphone Dialyzers. Kidney Internationale, 47(2), 573–578.
  • Krieter, D.H., Hackl, A., Rodriguez, A., Chenine, L., Moragues, H.L., Lemke, H.-D., et al. (2010). Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration. Nephrology Dialysis Transplantation, 25(1), 212-218.
  • Le Roy, F., Hanoy, M., Claeyssens, S., Bertrand, D., Freguia, C., Godin, M. (2009) Beta2-Microglobulin Removal and Albumin Losses in Post-Dilution Hemodiafiltration: Membrane Effect. Clin. KidneyJ., 2 (Suppl. 2), Sa402.
  • Maduell, F., Arias-Guillen, M., Fontsere, N., Ojeda, R., Rico, N., Vera, M., Elena, M., Bedini, J.L., Wieneke, P., Campistol, J.M. (2014) Elimination of Large Uremic Toxins by a Dialyzer Specifically Designed for High-Volume Convective Therapies. Blood Purification, 37(2), 125–130.
  • Shinzato, T., Miwa, M., Nakai, S., Takai, I., Matsumoto, Y., Morita, H., Miyata, T., Maeda, K. (1996) Alternate Repetition of Short Fore- and Back filtrations Reduces Convective Albumin Loss. Kidney Internationale, 50(2), 432–435.
  • Tırnakçı, B. Salt, Y., Salt, İ., Keyf, S. (2020). Klinoptilolit Dolgulu PVA Membranların Hazırlanması, Karakterizasyonu ve Pervaporasyon ile Desalinasyon Çalışmaları. Avrupa Bilim ve Teknoloji Dergisi, (18), 711-718.
  • Vanholder, R., Schepers, E., Pletinck, A., Neirynck, N. ve Glorieux, G. (2012). An Update on Protein-Bound Uremic Retention Solutes. Journal of Renal Nutrition, 22(1), 90–94.
  • Vanholder, R., Schepers, E., Pletinck, A., Nagler, E. V., & Glorieux, G. (2014). The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: A systematic review. Journal of American Society of Nephrology, 25(9), 1897-1907.
  • Yesil-Celiktas, O., Cumana, S., Smirnova, I. (2013). Silica-based monoliths for enzyme catalyzed reactions in microfluidic systems with an emphasis on glucose 6-phosphate dehydrogenase and cellulase. Chemical Engineering Journal, (234), 166-172.
  • Zweigart, C., Boschetti-de-Fierro, M., Neubauer, M., Storr, M., Böhler, T. ve Krause, B. (2017) Progress in the Development of Membranes for Kidney-Replacement Therapy. Comprehensive Membrane Science and Engineering (Second Edition) içinde (2. bs. Cilt 4, 214-247. ss.). Amsterdam: Elsevier B.V.

Modeling of Protein-Bound Uremic Toxin Adsorption in a Microfluidic Platform

Year 2021, Issue: 27, 354 - 361, 30.11.2021
https://doi.org/10.31590/ejosat.971386

Abstract

This study aims to develop a microfluidic platform that can be integrated into the hemodialysis system to find a solution to the uremic toxicity problem of chronic kidney patients. The hypothesis was tested which was the adsorption of one of the protein-bound uremic toxins in the blood, Indoxyl Sulfate (IS), can be achieved through the TEOS-PEO hydrogel, synthesized by sol-gel method and functionalized with Na-Y Zeolite, within the microfluidic chip. An S-shaped microchannel was designed with the Solidworks program, and simulation studies were carried out in the Comsol program. After the simulation studies, the detoxification of protein-bound indoxyl sulfate toxin from simulated blood fluid of Na-Y Zeolite-containing hydrogels, which were characterized by scanning electron microscopy and computerized micro-tomography analysis, was investigated both in batch conditions and in continuous mode in the developed microfluidic system. It is thought that this microfluidic design will contribute to the development of innovative methods that can remove protein-bound toxins that accumulate in the blood of chronic kidney patients in the clinic.

References

  • Armignacco P., Garzotto F., Neri M., Lorenzin A., Ronco C. (2015). Wak engineering evolution. Blood Purification, 39(1-3), 110-114. Caravaca, F., Arrobas, M. ve Dominguez, C. (2000). Serum Albumin and Other Serum Protein Fractions in Stable Patients on Peritoneal Dialysis. Peritoneal Dialysis International, (20), 703–707.
  • Davenport, A. (2014). How can dialyzer designs improve solute clearances for hemodialysis patients?. Hemodialysis International, 18(1), 43–47.
  • Eyüpoğlu, C. (2020). Kronik Böbrek Hastalığının Erken Tanısı için Yeni Bir Klinik Karar Destek Sistemi. Avrupa Bilim ve Teknoloji Dergisi, 20, 448-455.
  • Floege, J., Granolleras, C., Deschodt, G., Heck, M., Baudin, G., Branger, B., Tournier, O., Reinhard, B., Eisenbach, G.M., Smeby, L.C., et al. (1989). High-flux synthetic versus cellulosic membranes for beta 2-microglobulin removal during hemodialysis, hemodiafiltration and hemofiltration. Nephrology Dialysis Transplantation, 4(7), 653-657.
  • Gura, V., Rivara, M. B., Bieber, S., Munshi, R., Smith, N. C., Linke, L., et al. (2016). A wearable artificial kidney for patients with end-stage renal disease. JCI Insight, 1(8), e86397.
  • Ikizler, T. A., Flakoll, P.J., Parker, R.A., Hakim, R.M. (1994) Amino Acid and Albumin Losses During Hemodialysis. Kidney Internationale, 46(3), 830–837.
  • Kaplan, A.A., Halley, S.E., Lapkin, R.A., Graeber, C.W. (1995) Dialysate Protein Losses with Bleach Processed Polysulphone Dialyzers. Kidney Internationale, 47(2), 573–578.
  • Krieter, D.H., Hackl, A., Rodriguez, A., Chenine, L., Moragues, H.L., Lemke, H.-D., et al. (2010). Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration. Nephrology Dialysis Transplantation, 25(1), 212-218.
  • Le Roy, F., Hanoy, M., Claeyssens, S., Bertrand, D., Freguia, C., Godin, M. (2009) Beta2-Microglobulin Removal and Albumin Losses in Post-Dilution Hemodiafiltration: Membrane Effect. Clin. KidneyJ., 2 (Suppl. 2), Sa402.
  • Maduell, F., Arias-Guillen, M., Fontsere, N., Ojeda, R., Rico, N., Vera, M., Elena, M., Bedini, J.L., Wieneke, P., Campistol, J.M. (2014) Elimination of Large Uremic Toxins by a Dialyzer Specifically Designed for High-Volume Convective Therapies. Blood Purification, 37(2), 125–130.
  • Shinzato, T., Miwa, M., Nakai, S., Takai, I., Matsumoto, Y., Morita, H., Miyata, T., Maeda, K. (1996) Alternate Repetition of Short Fore- and Back filtrations Reduces Convective Albumin Loss. Kidney Internationale, 50(2), 432–435.
  • Tırnakçı, B. Salt, Y., Salt, İ., Keyf, S. (2020). Klinoptilolit Dolgulu PVA Membranların Hazırlanması, Karakterizasyonu ve Pervaporasyon ile Desalinasyon Çalışmaları. Avrupa Bilim ve Teknoloji Dergisi, (18), 711-718.
  • Vanholder, R., Schepers, E., Pletinck, A., Neirynck, N. ve Glorieux, G. (2012). An Update on Protein-Bound Uremic Retention Solutes. Journal of Renal Nutrition, 22(1), 90–94.
  • Vanholder, R., Schepers, E., Pletinck, A., Nagler, E. V., & Glorieux, G. (2014). The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: A systematic review. Journal of American Society of Nephrology, 25(9), 1897-1907.
  • Yesil-Celiktas, O., Cumana, S., Smirnova, I. (2013). Silica-based monoliths for enzyme catalyzed reactions in microfluidic systems with an emphasis on glucose 6-phosphate dehydrogenase and cellulase. Chemical Engineering Journal, (234), 166-172.
  • Zweigart, C., Boschetti-de-Fierro, M., Neubauer, M., Storr, M., Böhler, T. ve Krause, B. (2017) Progress in the Development of Membranes for Kidney-Replacement Therapy. Comprehensive Membrane Science and Engineering (Second Edition) içinde (2. bs. Cilt 4, 214-247. ss.). Amsterdam: Elsevier B.V.

Details

Primary Language Turkish
Subjects Engineering
Journal Section Articles
Authors

Esra İLHAN AYIŞIĞI This is me 0000-0003-1880-4261

Şeyma TIRAK This is me 0000-0002-1638-514X

Aylin ÖZÜNLÜ This is me 0000-0002-7094-3261

Ece YILDIZ ÖZTÜRK This is me 0000-0003-2482-7371

Özlem YEŞİL ÇELİKTAŞ 0000-0003-4509-2212

Project Number 2209/A
Early Pub Date July 29, 2021
Publication Date November 30, 2021
Published in Issue Year 2021 Issue: 27

Cite

APA İLHAN AYIŞIĞI, E., TIRAK, Ş., ÖZÜNLÜ, A., YILDIZ ÖZTÜRK, E., et al. (2021). Mikroakışkan Platformda Proteine Bağlı Üremik Toksin Adsorpsiyonunun Modellenmesi. Avrupa Bilim Ve Teknoloji Dergisi(27), 354-361. https://doi.org/10.31590/ejosat.971386