Dinamik Mikroakışkan Hücre Kültürü Platformlarında Difüzyon-Konveksiyon Proseslerinin Hesaplamalı Akışkanlar Dinamiği Modellemesi

Mikroakışkan tabanlı biyokimyasal analizler, hücre ve doku mühendisliğindeki son gelişmeler, mikroakışkan sistemler içinde uzaysal-zamansal olarak kütle transferinin kontrol edilmesine dayanmaktadır. Mikroakışkan sistemler ile hücresel mikroçevrenin kontrol edilmesi ve doku benzeri yapıların taklit edilmesinin yanısıra, yüksek verimli analizlerin gerçekleştirilmesinde de oldukça kullanışlı araçlardır. Bu sistemler biyoaktif moleküllerin, nütrientlerin, büyüme faktörlerinin ve diğer hücresel regülatör moleküllerin konsantrasyon gradientlerinin zamana ve konuma bağlı olarak kontrol etme potansiyeline sahiptir. Bu nedenle mikrosistemlerde biyomoleküllerin taşınım olaylarının modellenmesi, mikroakışkan platformların tasarımını ve kantitatif biyolojik analizleri kolaylaştıran değerli ve kullanışlı bir analitik araçtır. Geliştirilen analitik model mikroakışkan sistem tasarımına rehberlik ettiğinden; maliyetli ve zaman alıcı deneyler minimuma indirilebilmekte; tasarım süreci verimliliği ve etkinliği arttırılabilmektedir. Çalışma kapsamında ilaç taşınım uygulamalarına yönelik tek kanallı mikroakışkan platformda biyomoleküllerin difüzyon ve konveksiyon proseslerine vurgu yaparak kütle transferi profilini gösteren analitik bir model oluşturulmuştur. Mikroakışkan hücre kültürü sistemlerinin hücresel fizyolojik ortamların akış dinamiğini taklit edebilmesi için pulsatil laminar sıvı akışını sağlayabilen peristaltik pompa ile sistem kurulmuştur. Dinamik akış koşulları altında hücreler üzerine etki eden biyomekanik kuvvetlerin (akış hızı, konsantrasyon, basınç dağılımı ve kayma gerilimi) etkisini sayısal olarak incelemek için COMSOL Multiphysics sonlu elemanlar yazılımı kullanılarak mikroakışkan sistemin sayısal simülasyonu yapılmıştır. Mikroakışkan sistemde hücreler minimum kayma gerilimine maruz bırakılırken, kanal uzunluğu boyunca konsantrasyon profilinin korunduğu gösterilmiştir. Akış hızının arttırılmasıyla mikro kanal boyunca çözünen konsantrasyon dağılımı değiştirilebilmektedir ve bu da hücreler üzerindeki kayma gerilimini arttırmaktadır. Simülasyonu yapılan mikroakışkan analitik modelin, hücre kültürü, biyolojik analizler ve ilaç taşıyıcı sistemler için kullanılacak mikroakışkan platformların geliştirilmesinde sistem tasarımı ve parametre seçimi için temel olarak kullanılabileceği düşünülmüştür.

Anahtar Kelimeler:

Mikroakışkan hücre kültürü, difüzyon, konveksiyon, hesaplamalı akışkanlar dinamiği, matematiksel modelleme, Mikroakışkan hücre kültürü, difüzyon, konveksiyon, hesaplamalı akışkanlar dinamiği, matematiksel modelleme

Computational Fluid Dynamics Modeling of Diffusion-Convection Processes on Dynamic Microfluidic Cell Culture Platforms

Microfluidic-based biochemical analyzes and recent developments in cell/tissue engineering are based on controlling spatio-temporally mass transfer in microfluidic systems. These systems are useful tools for controlling the cellular microenvironment and simulating tissue-like structures, as well as performing high-throughput analysis. Therefore, modeling of transport processes of biomolecules in microsystems is a valuable and useful analytical tool that facilitates the design of microfluidic platforms and quantitative biological analysis. Within the scope of the study, an analytical model was created that shows the mass transfer profile by emphasizing the diffusion and convection processes of biomolecules in a single-channel microfluidic platform for drug transport applications. In order to mimic the flow dynamics of cellular physiological environments, the microsystem was established with a peristaltic pump that can provide pulsatile laminar fluid flow. Numerical simulation of the microsystem was performed using COMSOL software to numerically examine the effects of biomechanical forces (flow rate, concentration, pressure distribution and shear stress) acting on cells under dynamic flow conditions. In the microfluidic system, it has been shown that the concentration profile is maintained along the length of the channel while the cells are exposed to the minimum shear stress. By increasing the flow rate, the concentration distribution along the microchannel can be changed, increasing the shear stress on the cells. It is thought that the simulated microfluidic analytical model can be used as a basis for system design and parameter selection in the development of microfluidic platforms to be used for cell culture, biological analyzes and drug delivery systems.

Keywords:

Mikroakışkan hücre kültürü, difüzyon, konveksiyon, hesaplamalı akışkanlar dinamiği, matematiksel modelleme,

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