A modular 3D printed microfluidic system: a potential solution for continuous cell harvesting in large-scale bioprocessing

Lin Ding , Sajad Razavi Bazaz , Mahsa Asadniaye Fardjahromi , Flyn McKinnirey , Brian Saputro , Balarka Banerjee , Graham Vesey , Majid Ebrahimi Warkiani

Bioresources and Bioprocessing ›› 2022, Vol. 9 ›› Issue (1) : 64

PDF
Bioresources and Bioprocessing ›› 2022, Vol. 9 ›› Issue (1) : 64 DOI: 10.1186/s40643-022-00550-2
Research

A modular 3D printed microfluidic system: a potential solution for continuous cell harvesting in large-scale bioprocessing

Author information +
History +
PDF

Abstract

Microfluidic devices have shown promising applications in the bioprocessing industry. However, the lack of modularity and high cost of testing and error limit their implementation in the industry. Advances in 3D printing technologies have facilitated the conversion of microfluidic devices from research output to applicable industrial systems. Here, for the first time, we presented a 3D printed modular microfluidic system consisting of two micromixers, one spiral microfluidic separator, and one microfluidic concentrator. We showed that this system can detach and separate mesenchymal stem cells (MSCs) from microcarriers (MCs) in a short time while maintaining the cell’s viability and functionality. The system can be multiplexed and scaled up to process large volumes of the industry. Importantly, this system is a closed system with no human intervention and is promising for current good manufacturing practices.

Keywords

Microfluidics / Modular microfluidic system / Mesenchymal stem cells / 3D printing / Bioprocessing

Cite this article

Download citation ▾
Lin Ding, Sajad Razavi Bazaz, Mahsa Asadniaye Fardjahromi, Flyn McKinnirey, Brian Saputro, Balarka Banerjee, Graham Vesey, Majid Ebrahimi Warkiani. A modular 3D printed microfluidic system: a potential solution for continuous cell harvesting in large-scale bioprocessing. Bioresources and Bioprocessing, 2022, 9(1): 64 DOI:10.1186/s40643-022-00550-2

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Amini H, Lee W, Di Carlo D. Inertial microfluidic physics. Lab Chip, 2014, 14(15): 2739-2761.

[2]

Bhattacharjee N, . The upcoming 3D-printing revolution in microfluidics. Lab Chip, 2016, 16(10): 1720-1742.

[3]

Cai G, . A review on micromixers. Micromachines, 2017, 8(9): 274.

[4]

Caruso SR, . Growth and functional harvesting of human mesenchymal stromal cells cultured on a microcarrier-based system. Biotechnol Prog, 2014, 30(4): 889-895.

[5]

Castilho LR, Medronho RA. Cell retention devices for suspended-cell perfusion cultures. Tools and applications of biochemical engineering science, 2002, Berlin: Springer, 129-169.

[6]

Chai M, . Biocatalytic micromixer coated with enzyme-MOF thin film for CO2 conversion to formic acid. Chem Eng J, 2021, 426: 130856.

[7]

Chen AK-L, Reuveny S, Oh SKW. Application of human mesenchymal and pluripotent stem cell microcarrier cultures in cellular therapy: achievements and future direction. Biotechnol Adv, 2013, 31(7): 1032-1046.

[8]

Chen X-Y, . Recent advances in the use of microcarriers for cell cultures and their ex vivo and in vivo applications. Biotechnol Lett, 2020, 42(1): 1-10.

[9]

Chilima TDP, Moncaubeig F, Farid SS. Impact of allogeneic stem cell manufacturing decisions on cost of goods, process robustness and reimbursement. Biochem Eng J, 2018, 137: 132-151.

[10]

Cunha B, . Filtration methodologies for the clarification and concentration of human mesenchymal stem cells. J Membr Sci, 2015, 478: 117-129.

[11]

Di Carlo D. Inertial microfluidics. Lab Chip, 2009, 9(21): 3038-3046.

[12]

Ding L, . An easy-to-operate method for single-cell isolation and retrieval using a microfluidic static droplet array. Microchim Acta, 2021, 188(8): 1-11.

[13]

Ding L, . Giardia purification from fecal samples using rigid spiral inertial microfluidics. Biomicrofluidics, 2022, 16(1): 014105.

[14]

Fardjahromi MA, . Mussel inspired ZIF8 microcarriers: a new approach for large-scale production of stem cells. RSC Adv, 2020, 10(34): 20118-20128.

[15]

Ferrari C, . Limiting cell aggregation during mesenchymal stem cell expansion on microcarriers. Biotechnol Prog, 2012, 28(3): 780-787.

[16]

Figeys D, Pinto D. Lab-on-a-chip: a revolution in biological and medical sciences. Anal Chem, 2000, 72(9): 330A-335A.

[17]

Hanga MP, . Expansion of human mesenchymal stem/stromal cells (hMSCs) on temporary liquid microcarriers. J Chem Technol Biotechnol, 2021, 96: 930-940.

[18]

Ho CM, . 3D printed microfluidics for biological applications. Lab Chip, 2015, 15(18): 3627-3637.

[19]

Joseph A, . A scale-down mimic for mapping the process performance of centrifugation, depth and sterile filtration. Biotechnol Bioeng, 2016, 113(9): 1934-1941.

[20]

Jossen V, . Manufacturing human mesenchymal stem cells at clinical scale: process and regulatory challenges. Appl Microbiol Biotechnol, 2018, 102(9): 3981-3994.

[21]

Kalra K, . Developing efficient bioreactor microcarrier cell culture system for large scale production of mesenchymal stem cells (MSCs). Cytotherapy, 2019, 21(5): S73.

[22]

Lee WC, . Multivariate biophysical markers predictive of mesenchymal stromal cell multipotency. Proc Natl Acad Sci, 2014, 111(42): E4409-E4418.

[23]

Leuning DG, . The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment. Sci Rep, 2018, 8(1): 7716.

[24]

Mihandoust A, . High-throughput particle concentration using complex cross-section microchannels. Micromachines, 2020, 11(4): 440.

[25]

Moloudi R, . Inertial-based filtration method for removal of microcarriers from mesenchymal stem cell suspensions. Sci Rep, 2018, 8(1): 12481.

[26]

Moloudi R, . Scaled-up inertial microfluidics: retention system for microcarrier-based suspension cultures. Biotechnol J, 2019, 14(5): 1800674.

[27]

Najar M, . Immune-related antigens, surface molecules and regulatory factors in human-derived mesenchymal stromal cells: the expression and impact of inflammatory priming. Stem Cell Rev Rep, 2012, 8(4): 1188-1198.

[28]

Nasef A, . Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G. Transplantation, 2007, 84(2): 231-237.

[29]

Ng EX, . Dissolvable gelatin-based microcarriers generated through droplet microfluidics for expansion and culture of mesenchymal stromal cells. Biotechnol J, 2021, 16(3): 2000048.

[30]

Nienow AW, . Agitation conditions for the culture and detachment of hMSCs from microcarriers in multiple bioreactor platforms. Biochem Eng J, 2016, 108: 24-29.

[31]

Nivedita N, Ligrani P, Papautsky I. Dean flow dynamics in low-aspect ratio spiral microchannels. Sci Rep, 2017, 7: 44072.

[32]

Oh KW, . Design of pressure-driven microfluidic networks using electric circuit analogy. Lab Chip, 2012, 12(3): 515-545.

[33]

Ozbey A, . Inertial focusing of cancer cell lines in curvilinear microchannels. Micro Nano Eng, 2019, 2: 53-63.

[34]

Razavi Bazaz S, . Rapid soft lithography using 3D-printed molds. Adv Mater Technol, 2019, 4(10): 1900425.

[35]

Razavi Bazaz S, . 3D printing of inertial microfluidic devices. Sci Rep, 2020, 10(1): 5929.

[36]

Razavi Bazaz S, . Obstacle-free planar hybrid micromixer with low pressure drop. Microfluid Nanofluid, 2020, 24(8): 61.

[37]

Razavi Bazaz S, . Computational inertial microfluidics: a review. Lab Chip, 2020, 20(6): 1023-1048.

[38]

Rodrigues CA, Nogueira DE, Cabral JM. Next-generation stem cell expansion technologies. Cell Gene Ther Insights, 2018, 4(8): 791-804.

[39]

Rouhi O, . Numerical and experimental study of cross-sectional effects on the mixing performance of the spiral microfluidics. Micromachines, 2021, 12(12): 1470.

[40]

Rubtsov Y, . Molecular mechanisms of immunomodulation properties of mesenchymal stromal cells: a new insight into the role of ICAM-1. Stem Cells Int, 2017, 2017: 6516854.

[41]

Russell AL, Lefavor RC, Zubair AC. Characterization and cost-benefit analysis of automated bioreactor-expanded mesenchymal stem cells for clinical applications. Transfusion, 2018, 58(10): 2374-2382.

[42]

Schnitzler AC, . Bioprocessing of human mesenchymal stem/stromal cells for therapeutic use: current technologies and challenges. Biochem Eng J, 2016, 108: 3-13.

[43]

Selmani Z, . HLA-G is a crucial immunosuppressive molecule secreted by adult human mesenchymal stem cells. Transplantation, 2009, 87(9 Suppl): S62-S66.

[44]

Serra M, . Advancing manufacture of human mesenchymal stem cells therapies: technological challenges in cell bioprocessing and characterization. Curr Opin Chem Eng, 2018, 22: 226-235.

[45]

Tamura A, . Temperature-responsive poly(N-isopropylacrylamide)-grafted microcarriers for large-scale non-invasive harvest of anchorage-dependent cells. Biomaterials, 2012, 33(15): 3803-3812.

[46]

Tang B, . The therapeutic effect of ICAM-1-overexpressing mesenchymal stem cells on acute graft-versus-host disease. Cell Physiol Biochem, 2018, 46(6): 2624-2635.

[47]

Tavassoli H, . Large-scale production of stem cells utilizing microcarriers: a biomaterials engineering perspective from academic research to commercialized products. Biomaterials, 2018, 181: 333-346.

[48]

Tsui Y-Y, Yang C-S, Hsieh C-M. Evaluation of the mixing performance of the micromixers with grooved or obstructed channels. J Fluids Eng, 2008, 130(7): 071102.

[49]

Tsuji K, . Effects of different cell-detaching methods on the viability and cell surface antigen expression of synovial mesenchymal stem cells. Cell Transplant, 2017, 26(6): 1089-1102.

[50]

Vasilescu SA, . 3D printing enables the rapid prototyping of modular microfluidic devices for particle conjugation. Appl Mater Today, 2020, 20: 100726.

[51]

Wang L, Dandy DS. A microfluidic concentrator for cyanobacteria harvesting. Algal Res, 2017, 26: 481-489.

[52]

Xiang N, . Precise size-based cell separation via the coupling of inertial microfluidics and deterministic lateral displacement. Anal Chem, 2019, 91(15): 10328-10334.

[53]

Yin L, . Microfluidic label-free selection of mesenchymal stem cell subpopulation during culture expansion extends the chondrogenic potential in vitro. Lab Chip, 2018, 18(6): 878-889.

[54]

Yin L, . Label-free separation of mesenchymal stem cell subpopulations with distinct differentiation potencies and paracrine effects. Biomaterials, 2020, 240: 119881.

[55]

Yi-Qiang F, . Applications of modular microfluidics technology. Chin J Anal Chem, 2018, 46(12): 1863-1871.

[56]

Zydney AL. Continuous downstream processing for high value biological products: a review. Biotechnol Bioeng, 2016, 113(3): 465-475.

AI Summary AI Mindmap
PDF

100

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/