Caco-2 cell-derived biomimetic electrochemical biosensor for cholera toxin detection

Yonghwan Kim; Dongtak Lee; Youngjun Seo; Hyo Gi Jung; Jae Won Jang; Dongsung Park; Insu Kim; Jaeheung Kim; Gyudo Lee; Kyo Seon Hwang; Seung-Hyun Kim; Sang Won Lee; Jeong Hoon Lee; Dae Sung Yoon

doi:10.1016/j.bios.2023.115105

Caco-2 cell-derived biomimetic electrochemical biosensor for cholera toxin detection

Biosens Bioelectron. 2023 Apr 15:226:115105. doi: 10.1016/j.bios.2023.115105. Epub 2023 Jan 28.

Authors

Yonghwan Kim¹, Dongtak Lee², Youngjun Seo¹, Hyo Gi Jung¹, Jae Won Jang¹, Dongsung Park³, Insu Kim⁴, Jaeheung Kim¹, Gyudo Lee⁵, Kyo Seon Hwang⁶, Seung-Hyun Kim⁷, Sang Won Lee⁸, Jeong Hoon Lee⁹, Dae Sung Yoon¹⁰

Affiliations

¹ School of Biomedical Engineering, Korea University, Seoul, 02841, South Korea; Interdisciplinary Program in Precision Public Health, Korea University, Seoul, 02841, South Korea.
² School of Biomedical Engineering, Korea University, Seoul, 02841, South Korea; Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA; Harvard Medical School, Boston, MA, 02115, USA.
³ School of Biomedical Engineering, Korea University, Seoul, 02841, South Korea; Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, 02447, South Korea.
⁴ School of Biomedical Engineering, Korea University, Seoul, 02841, South Korea.
⁵ Department of Biotechnology and Bioinformatics, Korea University, Sejong, 30019, South Korea; Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong, 30019, South Korea.
⁶ Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, 02447, South Korea.
⁷ School of Engineering, Brown University, Providence, RI, 02912, USA.
⁸ School of Biomedical Engineering, Korea University, Seoul, 02841, South Korea; Department of Electrical Engineering and Computer Science, University of California, Irvine, CA, 92697, USA. Electronic address: skylsw5@korea.ac.kr.
⁹ Department of Electrical Engineering, Kwangwoon University, Seoul, 01897, South Korea. Electronic address: jhlee@kw.ac.kr.
¹⁰ School of Biomedical Engineering, Korea University, Seoul, 02841, South Korea; Interdisciplinary Program in Precision Public Health, Korea University, Seoul, 02841, South Korea; Astrion Inc, Seoul, 02841, South Korea. Electronic address: dsyoon@korea.ac.kr.

PMID: 36746024
DOI: 10.1016/j.bios.2023.115105

Abstract

Cholera is a highly contagious and lethal waterborne disease induced by an infection with Vibrio cholerae (V. cholerae) secreting cholera toxin (CTx). Cholera toxin subunit B (CTxB) from the CTx specifically binds with monosialo-tetra-hexosyl-ganglioside (GM1) found on the exterior cell membrane of an enterocyte. Bioinspired by the pathological process of CTx, we developed an electrochemical biosensor with GM1-expressing Caco-2 cell membrane (CCM) on the electrode surface. Briefly, the electrode surface was functionalized with CCM using the vesicle fusion method. We determined the CTxB detection performances of Caco-2 cell membrane-coated biosensor (CCB) using electrochemical impedance spectroscopy (EIS). the CCB had an excellent limit of detection of ∼11.46 nM and a detection range spanning 100 ng/mL - 1 mg/mL. In addition, the CCB showed high selectivity against various interfering molecules, including abundant constituents of intestinal fluid and various bacterial toxins. The long-term stability of the CCBs was also verified for 3 weeks using EIS. Overall, the CCB has excellent potential for practical use such as point-of-care and cost-effective testing for CTxB detection in developing countries.

Keywords: Bioinspired; Biosensor; Caco-2 cell membrane; Cholera; Cholera toxin subunit B; Electrochemical impedance spectroscopy.

MeSH terms

Biomimetics
Biosensing Techniques*
Caco-2 Cells
Cholera Toxin
Cholera* / microbiology
G(M1) Ganglioside
Humans

Substances

Cholera Toxin
G(M1) Ganglioside