Inkjet-Printed Liquid Gated Graphene Field Effect Transistor for the Detection of Interleukin-6

Abstract:

Interleukin-6 (IL-6) is an inflammatory cytokine that serves as an important prognostic biomarker for chronic diseases such as cancer and coronavirus disease. Label-free sensors that can conveniently detect IL-6 are essential for health monitoring purposes. Here, we present an aptamer-modified liquid-gated graphene field effect transistor (GFET) biosensor fabricated using inkjet printing techniques that can detect IL-6 levels. In this work, graphene ink suitable for inkjet printing was synthesized and formulated using the ultrasonic liquid exfoliation method. Exfoliated graphene was redispersed into a cyclohexanone/terpineol solvent system and optimized to achieve jettable ink with a Z-number of 13.7. The formulated graphene ink was then used to fabricate the GFET device, which in turn was decorated with IL-6 aptamer using organic linkers. The sensor response of the GFET was measured using the shift in the transistor current-voltage (I-V) transfer curves upon specific binding of the IL-6 with the aptameric GFET. The experimental results showed that the device can sensitively and selectively detect IL-6 in a 1xPBS background with a limit of detection of 372 pM. The fabricated GFET is on a flexible substrate that may be suitably incorporated into a face mask covering that could potentially sample IL-6 from collected saliva.

• Periodical: Solid State Phenomena (Volume 367)
• Pages: 33-40
• DOI: https://doi.org/10.4028/p-olQb7r
• Online since: December 2024
• Authors: Al Vincent Amigo Jabines, Erwin P. Enriquez*
• Keywords: Aptamer, Graphene, Graphene Field-Effect Transistor, Nanomaterials, Printed Electronics

References

[1] Russell, S. M., Alba-Patiño, A., Barón, E., Borges, M., Gonzalez-Freire, M., & de la Rica, R. (2020). Biosensors for managing the COVID-19 cytokine storm: challenges ahead. ACS sensors, 5(6), 1506-1513.

DOI: 10.1021/acssensors.0c00979

[2] Liu, G., Jiang, C., Lin, X., & Yang, Y. (2021). Point‐of‐care detection of cytokines in cytokine storm management and beyond: Significance and challenges. View, 2(4), 20210003.

DOI: 10.1002/viw.20210003

[3] Hu, B., Huang, S., & Yin, L. (2021). The cytokine storm and COVID‐19. Journal of medical virology, 93(1), 250-256.

[4] Aziz, M., Fatima, R., & Assaly, R. (2020). Elevated interleukin‐6 and severe COVID‐19: a meta‐analysis. Journal of medical virology, 92(11), 2283.

DOI: 10.1002/jmv.25948

[5] Sabaka, P., Koščálová, A., Straka, I., Hodosy, J., Lipták, R., Kmotorková, B., ... & Kušnírová, A. (2021). Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a long-term care facility during Covid-19 outbreak. BMC infectious diseases, 21, 1-8.

DOI: 10.1186/s12879-021-05945-8

[6] Rašková, M., Lacina, L., Kejík, Z., Venhauerová, A., Skaličková, M., Kolář, M., ... & Brábek, J. (2022). The role of IL-6 in cancer cell invasiveness and metastasis—overview and therapeutic opportunities. Cells, 11(22), 3698.

DOI: 10.3390/cells11223698

[7] Forsyth, R., Devadoss, A., & Guy, O. J. (2017). Graphene field effect transistors for biomedical applications: Current status and future prospects. Diagnostics, 7(3), 45.

DOI: 10.3390/diagnostics7030045

[8] Hao, Z., Luo, Y., Huang, C., Wang, Z., Song, G., Pan, Y., ... & Liu, S. (2021). An intelligent graphene‐based biosensing device for cytokine storm syndrome biomarkers detection in human biofluids. Small, 17(29), 2101508.

DOI: 10.1002/smll.202101508

[9] Kumar, M. A., Jayavel, R., Mahalingam, S., Kim, J., & Atchudan, R. (2023). Detection of Interleukin-6 Protein Using Graphene Field-Effect Transistor. Biosensors, 13(9), 834.

DOI: 10.3390/bios13090834

[10] Laliberte, K. E., Scott, P., Khan, N. I., Mahmud, M. S., & Song, E. (2022). A wearable graphene transistor-based biosensor for monitoring IL-6 biomarker. Microelectronic Engineering, 262, 111835.

DOI: 10.1016/j.mee.2022.111835

[11] Wang, Z., Hao, Z., Wang, X., Huang, C., Lin, Q., Zhao, X., & Pan, Y. (2021). A flexible and regenerative aptameric graphene–nafion biosensor for cytokine storm biomarker monitoring in undiluted biofluids toward wearable applications. Advanced Functional Materials, 31(4), 2005958.

DOI: 10.1002/adfm.202005958

[12] Spiridonova, V. A., Novikova, T. M., & Snigirev, O. V. (2016). Obtaining DNA aptamers to human interleukin-6 for biomagnetic immunoassay nanosensors. Moscow University Physics Bulletin, 71, 135-138.

DOI: 10.3103/s002713491601015x

[13] Wei, Y., & Sun, Z. (2015). Liquid-phase exfoliation of graphite for mass production of pristine few-layer graphene. Current opinion in colloid & interface science, 20(5-6), 311-321.

DOI: 10.1016/j.cocis.2015.10.010

[14] Zhang, R., & Jia, Y. (2021). A disposable printed liquid gate graphene field effect transistor for a salivary cortisol test. ACS sensors, 6(8), 3024-3031.

DOI: 10.1021/acssensors.1c00949

[15] Jang, D., Kim, D., & Moon, J. (2009). Influence of fluid physical properties on ink-jet printability. Langmuir, 25(5), 2629-2635.

DOI: 10.1021/la900059m

[16] Graf, D., Molitor, F., Ensslin, K., Stampfer, C., Jungen, A., Hierold, C., & Wirtz, L. (2007). Spatially resolved Raman spectroscopy of single-and few-layer graphene. Nano letters, 7(2), 238-242.

DOI: 10.1021/nl061702a

[17] Nguyen, N. H. L., Kim, S., Lindemann, G., & Berry, V. (2021). COVID-19 spike protein induced phononic modification in antibody-coupled graphene for viral detection application. ACS nano, 15(7), 11743-11752.

DOI: 10.1021/acsnano.1c02549