Enhanced Design and Analysis of the Microcantilever-Based Bio-Sensor to Detect Carcinoembryonic Antigen Tumor Biomarkers

  • Khalid Mohd Ibrahimi Department of Electronics and Instrumentation Engineering, National Institute of Technology, Nagaland, India
  • Rajagopal Kumar Department of Electronics and Instrumentation Engineering, National Institute of Technology, Nagaland, India
  • Writtick Pakhira Department of Electronics and Instrumentation Engineering, National Institute of Technology, Nagaland, India
  • Fenil C. Panwala Department of Electronics and Instrumentation Engineering, Siddaganga Institute of Technology, India

Abstract

Frequently, early detection of a malignant condition prevents most premature deaths. In this paper, three new designs are proposed for the microcantilever-based biosensor to detect carcinoembryonic antigen (CEA) tumor biomarkers. CEA is used for several types of human cancers, e.g., lung cancer, pancreatic cancer, breast cancer, ovarian cancer, and gastric cancer, particularly colorectal cancer. The proposed models are designed and the finite element method (FEM) analysis of these biosensors is performed using a COMSOL 5.4 Multiphysics (commercial package) software. Various analyses and comparisons are carried out by utilizing the designs in terms of displacement as well as piezo-resistive output due to an increase in mass of CEA adsorbed onto the surface of the cantilever beam, which is stimulated by applying a pressure range of 0 to 0.2 Pa on to the surface of a cantilever beam. A simulation is performed with the proposed designs by experimenting with different materials for better deflection results. Regarding the results obtained, Design 3, made with Kynar710, gives the highest total deflection of 0.7328 m. However, a piezo-resistive readout technique is utilized to get the output in mV, and for that, p-silicon (single-crystal, lightly doped) material is used, respectively. Next, 5V is applied to the terminals of the piezo-resistive circuit. Based on the input applied pressure and output mV, the Design 3 made with Kynar710 gives a better sensitivity of 0.13089 [mV/V/Pa] compared to other designs made with other materials.

Keywords

carcinoembryonic antigen, microcantilever, piezoresistive, tumor biomarkers,

References

1. D. Di Gioia, I. Blankenburg, D. Nagel, V. Heinemann, P. Stieber, Tumor markers in the early detection of tumor recurrence in breast cancer patients: CA 125, CYFRA 21-1, HER2 shed antigen, LDH, and CRP in combination with CEA and CA 15-3, Clinica Chimica Acta, 461: 1–7, 2016, doi: 10.1016/j.cca.2016.07.014.
2. G. Lech, R. Słotwinski, M. Słodkowski, I.W. Krasnodebski, Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances, World Journal of Gastroenterology, 22(5): 1745–1755, 2016, doi: 10.3748/wjg.v22.i5.1745.
3. P. Gold, S.O. Freedman, Specific carcinoembryonic antigens of the human digestive system, The Journal of Experimental Medicine, 122(3): 467–481, 1965, doi: 10.1084/jem.122.3.467.
4. R.H. Fletcher, Carcinoembryonic antigen, Annals of Internal Medicine, 104(1): 66–73, 1986, doi: 10.7326/0003-4819-104-1-66.
5. C.O. Sahlmann et al., Repeated adjuvant anti-CEA radioimmunotherapy after resection of colorectal liver metastases: safety, feasibility, and long-term efficacy results of a prospective phase 2 study, Cancer, 123(4): 638–649, 2017, doi: 10.1002/cncr.30390.
6. G. Saito, S. Sadahiro, K. Okada, A. Tanaka, T. Suzuki, A. Kamijo, Relation between carcinoembryonic antigen levels in colon cancer tissue and serum carcinoembryonic antigen levels at initial surgery and recurrence, Oncology, 91(2): 85–89, 2016, doi: 10.1159/000447062.
7. K.L.G. Spindler et al., Total cell-free DNA, carcinoembryonic antigen, and C-reactive protein for assessment of prognosis in patients with metastatic colorectal cancer, Tumor Biology, 40(11): 1–8, 2018, doi: 10.1177/1010428318811207.
8. E. Tan, N. Gouvas, R.J. Nicholls, P. Ziprin, E. Xynos, P.P. Tekkis, Diagnostic precision of carcinoembryonic antigen in the detection of recurrence of colorectal cancer, Surgical Oncology, 18(1): 15–24, 2009, doi: 10.1016/j.suronc.2008.05.008.
9. M. Salve, M. Dhone, P. Rewatkar, S. Balpande, J. Kalambe, Design and sensitivity analysis of micro-cantilever based biosensor for tumor detection, Sensor Letters, 17(1): 64–68, 2019, doi: 10.1166/sl.2019.3981.
10. A.M. Upadhyaya, M.C. Srivastava, P. Sharan, Integrated MOEMS based cantilever sensor for early detection of cancer, Optik, 227: 165321, 2021, doi: 10.1016/j.ijleo.2020.165321.
11. W. Xiang, Q. Lv, H. Shi, B. Xie, L. Gao, Aptamer-based biosensor for detecting carcinoembryonic antigen, Talanta, 214: 120716, 2020, doi: 10.1016/j.talanta.2020.120716.
12. C. Li, X. Ma, Y. Guan, J. Tang, B. Zhang, Microcantilever array biosensor for simultaneous detection of carcinoembryonic antigens and alpha-fetoprotein based on real-time monitoring of the profile of cantilever, ACS Sensors, 4(11): 3034–3041, 2019, doi: 10.1021/acssensors.9b01604.
13. R.M.R. Pinto, V. Chu, J.P. Conde, Label-free biosensing of DNA in microfluidics using amorphous silicon capacitive micro-cantilevers, IEEE Sensors Journal, 20(16): 9018–9028, 2020, doi: 10.1109/JSEN.2020.2986497.
14. G.S. Lakshmi, K.S. Rao, K. Guha, K.G. Sravani, Design of piezoresistive-based microcantilever for MEMS pressure sensor in continuous glucose monitoring system, [in:] Micro and Nanoelectronics Devices, Circuits and Systems, pp. 371–379, Springer, Singapore, 2022, doi: 10.1007/978-981-16-3767-4_35.
15. D.R. Rotake, A.D. Darji, Stiffness and sensitivity analysis of microcantilever based piezoresistive sensor for bio-MEMS application, [in:] 2018 IEEE Sensors, pp. 1–4, IEEE, 2018, doi: 10.1109/ICSENS.2018.8589732.
16. M.A. Andrade et al., A nanomechanical genosensor using functionalized cantilevers to detect the cancer biomarkers miRNA-203 and miRNA-205, IEEE Sensors Journal, 20(6): 2860–2867, 2019, doi: 10.1109/JSEN.2019.2948506.
17. S.S. Kumar, A.K. Ojha, R. Nambisan, A.K. Sharma, B.D. Pant, Design and simulation of MEMS silicon piezoresistive pressure sensor for barometric applications, Proceedings of the ARTCom&ARTEE PEIE&itSIP and PCIE, pp. 339–345, Elsevier, 2013.
18. N.V. Lavrik, M.J. Sepaniak, P.G. Datskos, Cantilever transducers as a platform for chemical and biological sensors, Review of Scientific Instruments, 75(7): 2229–2253, 2004, doi: 10.1063/1.1763252.
19. H.P. Lang, C. Gerber, Microcantilever sensors, [in:] STM and AFM Studies on (Bio)molecular Systems: Unravelling the Nanoworld, P. Samorì [Ed.], vol. 285, pp. 1–27, Springer, Berlin, Heidelberg, 2008, doi: 10.1007/128_2007_28.
20. D. Rotake, A. Darji, N. Kale, Fabrication, calibration, and preliminary testing of microcantilever-based piezoresistive sensor for BioMEMS applications, IET Nanobiotechnology, 14(5): 357–368, 2020, doi: 10.1049/iet-nbt.2019.0277.
21. U. Eswaran, S. Anand, Design and analysis of high sensitive microcantilever based biosensor for CA 15-3 biomarker detection, Journal of Applied Science and Computations, 5(7): 682–698, 2019, https://www.semanticscholar.org/paper/Design-and-Analysis-of-High-Sensitive-Based-for-CA-Eswaran-Anand/12f1767a37e6c8e6f3a8dbacae7743e676c483fa.
22. A MEMS Clearinghouser and information portal for the MEMS and Nanotechnology community, https://www.memsnet.org/material/.
23. Polymethylmethacrylate (PMMA, Acrylic), MakeItFrom.com, https://www.makeitfrom.com/material-properties/Polymethylmethacrylate-PMMA-Acrylic.
24. CAMPUSplastics, datasheet Kynarr 710, https://www.campusplastics.com/campus/en/datasheet/KYNAR+710/ARKEMA/179/90db57cc.
25. M. Bao, Analysis and design principles of MEMS devices, Elsevier, 2005.
Published
Jun 30, 2023
How to Cite
IBRAHIMI, Khalid Mohd et al. Enhanced Design and Analysis of the Microcantilever-Based Bio-Sensor to Detect Carcinoembryonic Antigen Tumor Biomarkers. Computer Assisted Methods in Engineering and Science, [S.l.], v. 30, n. 3, p. 347–367, june 2023. ISSN 2956-5839. Available at: <https://cames.ippt.pan.pl/index.php/cames/article/view/654>. Date accessed: 15 nov. 2024. doi: http://dx.doi.org/10.24423/cames.654.
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Articles