TY - JOUR
T1 - Timescale analysis for estimating upper limit perfusion rate in a microfluidic perfusion cell culture platform
AU - Maeng, Joon Ho
AU - Jeong, Hyo Eun
AU - Shin, Hyun Joon
AU - Kim, Sehoon
AU - Lee, Jong Chul
AU - Lee, Jaeyoung
AU - Chung, Seok
AU - Lee, Sangyoup
N1 - Funding Information:
This work was supported by the KIST Institutional Program (2E24700) and by Convergence Technology Development Program (S2096502) of Small and Medium Business Administration of Korea. S. Chung was supported by NRF (2012-022481) and Human Energy, Republic of Korea (20124010203250).
Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Proliferation characteristics of CHO-K1 cells were investigated under a variety of medium perfusion rate conditions in a microfluidic perfusion cell culture platform. Five microcavities of $$800\,\upmu \hbox {m}~(w)\,\times \,800\,\upmu \hbox {m}~(l)\,\times \,400\,\upmu \hbox {m}~(h)$$800μm(w)×800μm(l)×400μm(h) were adopted in order to minimize or isolate the shear effects on cell surfaces. Microchannels of $$800\,\upmu \hbox {m}~(w)\,\times \,3.5\,\hbox {mm}~(l)\,\times \,100\,\upmu \hbox {m}~(h)$$800μm(w)×3.5mm(l)×100μm(h) serially connecting these microcavities created flow contractions and expansions repeatedly, resulting in two different diffusion and convection timescales through the platform. Average shear stresses on the bottom of microcavity were both numerically and analytically estimated, and medium flow was operated at rates where shear stress is below $$\sim$$∼2 mPa. Proliferation rates of CHO-K1 cells were investigated based both on population groups derived from the number of initially seeded cells and on the microcavity locations. Population groups showed minimal influences on proliferation rates, while proliferation rates increased clearly with medium perfusion rates. Strong effects of microcavity locations were observed on proliferation at $$\hbox {Pe}\,\ge \,45$$Pe≥45. Such effects were analyzed by investigating the relationships of reaction, diffusion, and convection timescales associated with perfusion conditions. The ratio of diffusion timescale and convection timescale was suggested as a guideline to estimate the upper limit of perfusion rate in microfluidic perfusion cell culture platform.
AB - Proliferation characteristics of CHO-K1 cells were investigated under a variety of medium perfusion rate conditions in a microfluidic perfusion cell culture platform. Five microcavities of $$800\,\upmu \hbox {m}~(w)\,\times \,800\,\upmu \hbox {m}~(l)\,\times \,400\,\upmu \hbox {m}~(h)$$800μm(w)×800μm(l)×400μm(h) were adopted in order to minimize or isolate the shear effects on cell surfaces. Microchannels of $$800\,\upmu \hbox {m}~(w)\,\times \,3.5\,\hbox {mm}~(l)\,\times \,100\,\upmu \hbox {m}~(h)$$800μm(w)×3.5mm(l)×100μm(h) serially connecting these microcavities created flow contractions and expansions repeatedly, resulting in two different diffusion and convection timescales through the platform. Average shear stresses on the bottom of microcavity were both numerically and analytically estimated, and medium flow was operated at rates where shear stress is below $$\sim$$∼2 mPa. Proliferation rates of CHO-K1 cells were investigated based both on population groups derived from the number of initially seeded cells and on the microcavity locations. Population groups showed minimal influences on proliferation rates, while proliferation rates increased clearly with medium perfusion rates. Strong effects of microcavity locations were observed on proliferation at $$\hbox {Pe}\,\ge \,45$$Pe≥45. Such effects were analyzed by investigating the relationships of reaction, diffusion, and convection timescales associated with perfusion conditions. The ratio of diffusion timescale and convection timescale was suggested as a guideline to estimate the upper limit of perfusion rate in microfluidic perfusion cell culture platform.
UR - http://www.scopus.com/inward/record.url?scp=84942982343&partnerID=8YFLogxK
U2 - 10.1007/s10404-015-1602-4
DO - 10.1007/s10404-015-1602-4
M3 - Article
AN - SCOPUS:84942982343
SN - 1613-4982
VL - 19
SP - 777
EP - 786
JO - Microfluidics and Nanofluidics
JF - Microfluidics and Nanofluidics
IS - 4
ER -