LIVER-ON-A-CHIP: TOWARDS EMULATION OF DRUG METABOLISM IN A MICROFLUIDIC PLATFORM

Gulsim Kulsharova; Akbota Kurmangaliyeva; Galiya Toxeitova; Elvira Darbayeva; Aidos Baumuratov; Luis Rojas-Solórzano

LIVER-ON-A-CHIP: TOWARDS EMULATION OF DRUG METABOLISM IN A MICROFLUIDIC PLATFORM

Gulsim Kulsharova
, Akbota Kurmangaliyeva
, Galiya Toxeitova
, Elvira Darbayeva
, Aidos Baumuratov
, Luis Rojas-Solórzano

Nazarbayev University

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Abstract

The drug development process can benefit from the effective screening of toxic metabolites early on. To improve our previous efforts of drug metabolism investigation efforts using enzymatic microfluidic platforms, we have developed a cell-based perfused microfluidic device as a first step towards the drug metabolism mimicry in a chip. Here, we report a liver-on-a-chip device with computational fluid dynamics, cell growth, and assessment of cell functionality results.

Original language	English
Title of host publication	MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences
Publisher	Chemical and Biological Microsystems Society
Pages	441-442
Number of pages	2
ISBN (Electronic)	9781733419031
Publication status	Published - 2021
Event	25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021 - Palm Springs, Virtual, United States Duration: Oct 10 2021 → Oct 14 2021

Publication series

Name	MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences

Conference

Conference	25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021
Country/Territory	United States
City	Palm Springs, Virtual
Period	10/10/21 → 10/14/21

Funding

conditions that may cause the formation of possible air bubbles in the chamber. Due to the memory and CPU-time limitations associated with this simulation, the geometry was halved by cutting through its symmetry plane (Fig.2A). The free surface and the air volume remaining in the chamber during the filling process with the liquid were modeled using the compressed multiphase algorithm present in the CFD platform ANSYS-CFX. The air volume present in the device was calculated only for the chamber and its inlet-outlet tubings, ignoring the vertical tubing collector located in the outlet (see Fig. 2A). This provided a more precise calculation of the amount of entrapped air in the LOC main body region after the filling process ended. Results showed that after completing the filling process, there was still an 18% of volume occupied by air. Experimentally in a continuous flow through the device bubble-entrapment was not observed at slow flow rates. The LOC design allowed for monitoring of the culture environment by direct access to the chamber via a heating stage that can support the temperature of 37 oC during the experiment. Optical microscopy showed confluent and intact cell culture before and after continuous-flow through the LOC (Fig.2B/C) for 4-5 h. The cells remained attached to the PC chamber surface. A short evaluation study was carried out to assess the functionality of the Huh7 culture in the LOC. Equal volume fractions of the flow-through were collected. Albumin production per cultured number of cells, time, and volume of the sample was comparable and found to be in the range of values of albumin secreted in traditional 2D static cell cultures (Fig. 2D). Although the functionality of LOC cell culture in the perfused system needs to be investigated further, this work provides an initial proof-of-concept demonstration of the utility of the developed LOC device platform, which will be applied for drug metabolism assessment in future studies. CONCLUSION We described a microphysiological liver-on-a-chip (LOC) platform towards the development of an on-chip rapid analysis of novel drug compounds. The results showed the first proof-of-concept study of the LOC device. Further work contains the optimization of functionality of cell culture in the device, design improvements, and application of the LOC to drug metabolism and drug screening studies. ACKNOWLEDGEMENTS The funding was provided by the Nazarbayev University Faculty-development research grant (080420FD1910), the Ministry of Education and Science of the Republic of Kazakhstan Grant for young researchers (AP09058308). The authors thank Dr. Zhussipbek Mukhatayev for providing cells. REFERENCES [1] Kulsharova, G., Mimicking Human Drug Metabolic Reactions using Microfluidic Platforms. UCL. [2] Kulsharova, G., Proceedings of Micro Total Analysis Systems 2016, Dublin, Ireland. [3] Kampe, T. et al., Analytical chemistry, 86(6), pp.3068-3074. CONTACT * Gulsim Kulsharova; [email protected]

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 6 Clean Water and Sanitation
SDG 7 Affordable and Clean Energy
SDG 9 Industry, Innovation, and Infrastructure
SDG 11 Sustainable Cities and Communities

Keywords

drug metabolism
liver-on-a-chip
microfluidic platform
microphysiological system

ASJC Scopus subject areas

Bioengineering
Chemical Engineering (miscellaneous)

Cite this

Kulsharova, G., Kurmangaliyeva, A., Toxeitova, G., Darbayeva, E., Baumuratov, A., & Rojas-Solórzano, L. (2021). LIVER-ON-A-CHIP: TOWARDS EMULATION OF DRUG METABOLISM IN A MICROFLUIDIC PLATFORM. In MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (pp. 441-442). (MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences). Chemical and Biological Microsystems Society.

LIVER-ON-A-CHIP: TOWARDS EMULATION OF DRUG METABOLISM IN A MICROFLUIDIC PLATFORM. / Kulsharova, Gulsim; Kurmangaliyeva, Akbota; Toxeitova, Galiya et al.
MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. Chemical and Biological Microsystems Society, 2021. p. 441-442 (MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Kulsharova, G, Kurmangaliyeva, A, Toxeitova, G, Darbayeva, E, Baumuratov, A & Rojas-Solórzano, L 2021, LIVER-ON-A-CHIP: TOWARDS EMULATION OF DRUG METABOLISM IN A MICROFLUIDIC PLATFORM. in MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Chemical and Biological Microsystems Society, pp. 441-442, 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021, Palm Springs, Virtual, United States, 10/10/21.

Kulsharova G, Kurmangaliyeva A, Toxeitova G, Darbayeva E, Baumuratov A, Rojas-Solórzano L. LIVER-ON-A-CHIP: TOWARDS EMULATION OF DRUG METABOLISM IN A MICROFLUIDIC PLATFORM. In MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. Chemical and Biological Microsystems Society. 2021. p. 441-442. (MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences).

Kulsharova, Gulsim ; Kurmangaliyeva, Akbota ; Toxeitova, Galiya et al. / LIVER-ON-A-CHIP : TOWARDS EMULATION OF DRUG METABOLISM IN A MICROFLUIDIC PLATFORM. MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. Chemical and Biological Microsystems Society, 2021. pp. 441-442 (MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences).

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abstract = "The drug development process can benefit from the effective screening of toxic metabolites early on. To improve our previous efforts of drug metabolism investigation efforts using enzymatic microfluidic platforms, we have developed a cell-based perfused microfluidic device as a first step towards the drug metabolism mimicry in a chip. Here, we report a liver-on-a-chip device with computational fluid dynamics, cell growth, and assessment of cell functionality results.",

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AU - Toxeitova, Galiya

AU - Darbayeva, Elvira

AU - Baumuratov, Aidos

AU - Rojas-Solórzano, Luis

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ER -

LIVER-ON-A-CHIP: TOWARDS EMULATION OF DRUG METABOLISM IN A MICROFLUIDIC PLATFORM

Abstract

Publication series

Conference

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

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Cite this