Thermal Performance Simulation of an LTCC Micro-Reactor for RT-PCR in Detection of SARS-Cov-2 Detection


  • Lokesh Kulhari Karnataka Hybrid Micro device Pvt Ltd, Bangalore, Karnataka 560100, India
  • Nikhil Suri CSIR- Central Electronics Engineering Research Institute, Pilani, India- 333031, India
  • Badrul Hisham Ahmad Faculty of Electronic and Computer Engineering, Universiti Teknikal Malaysia Melaka, Melaka, Malaysia
  • Preecha Yupapin Department of Electrical Technology, School of Industrial Technology, Institute of Vocational Education Northeastern 2, Sakonnakhorn 47000, Thailand
  • Kanad Ray AMITY University Rajasthan, Jaipur, Rajasthan 303002, India


LTCC, Micro-reactor, COVID-19, Polymerase chain reaction


In present paper, thermal simulation of LTCC based micro-chamber has been performed which is a key part of RT-PCR device. The RT-PCR device plays an important role in SARS-CoV-2 testing. The rRT-PCR system requires three different thermal cycles for DNA amplification which takes part in detection of SARS-CoV-2. The thermal cycle can be equipped using a heater structure in the chamber. A new LTCC based technique to develop micro-chamber has been designed and simulation has been performed using COMSOL to optimize thermal properties. Temperature distribution for  a micro-chamber at three different voltages has been simulated. The temperature distribution is more uniform in  micro-chamber with a buried metallic layer in comparision to micro-chamber without a metallic layer. The heater and temperature sensor were located outside the reaction chamber. A platinum based pattern as PTC temperature sensor is used in temperature measurement.


N. Zhu, D. Zhang, W. Wang, , X Li., B. Yang, J. Song, X. Zhao, B. Huang, W. Shi, R. Lu, and P. Niu, “A novel coronavirus from patients with pneumonia in China, 2019,” New England Journal of Medicine, 2020.

I. Astuti, “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response,” Diabetes & Metabolic Syndrome: Clinical Research & Reviews; 2020.

C. Huang, Y. Huang, X. Li et al “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China,” Lancet. 2020; 395; 497–506

J. Chen, L. Wu, J. Zhang, L. Zhang, D. Gong, Y. Zhao, S. Hu, Y. Wang, X. Hu, B. Zheng et al.

“Deep learning-based model for detecting 2019 novel coronavirus pneumonia on high-resolution computed tomography: a prospective study,” medRxiv. 2020.

WHO Recommended Surveillance Standards WHO/CDS/CSR/ISR/99.2 (

Huang, Chaolin, et al. “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China." The lancet. 2020; 395(10223); 497-506.

D. Wang, BB. Hu, C Hu, F. Zhu, X.. Liu, J. Zhang, B. Wang, H. Xiang, Z. Cheng, Y. Xiong, y. Zhao, “Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China,” Jama. 2020; 323(11): 1061-9.

Y. Gao, L. Yan, Y. Huang, F. Liu, Y. Zhao, L. Cao, T. Wang, Q. Sun, Z. Ming, L. Zhang, J. Ge, “Structure of the RNA-dependent RNA polymerase from COVID-19 virus,” Science. 2020 May 15;368(6492):779-82.

A.C. Walls, Y.J. Park, M.A. Tortorici, A. Wall, A.T. McGuire, D. Veesler, “Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein,” Cell. 2020 Mar 9.

Y. Watanabe, J.D. Allen, D. Wrapp, J.S. McLellan, M. Crispin, “Site-specific glycan analysis of the SARS-CoV-2 spike,” Science. 2020 May 4.

L. Mousavizadeh, S. Ghasemi, “Genotype and phenotype of COVID-19: Their roles in pathogenesis,” Journal of Microbiology, Immunology and Infection. 2020 Mar 31.

D. Schoeman, BC. Fielding, “Coronavirus envelope protein: current knowledge,” Virology journal, 2019 Dec; 16(1):1-22.

C. Xie, L Jiang, G. Huang, H. Pu, B. Gong, H. Lin, S. Ma, X. Chen, B. Long, Si G, H. Yu, ”Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests,” International Journal of Infectious Diseases. 2020 Feb 27.

D. Jacofsky, E.M. Jacofsky, M. Jacofsky, “Understanding antibody testing for covid-19,” The Journal of Arthroplasty. 2020 Apr 27.

J.J. Deeks, J Dinnes, Y. Takwoingi, C. Davenport, Mm Leeflang, .R Spijker, L Hooft, A Van den Bruel, D Emperador, S. Dittrich “Diagnosis of SARS‐CoV‐2 infection and COVID‐19: accuracy of signs and symptoms; molecular, antigen, and antibody tests; and routine laboratory markers,” Cochrane Database of Systematic Reviews. 2020(4).

A. Scohy, A. Anantharajah, M. Bodéus, B. Kabamba-Mukadi, A. Verroken, H Rodriguez-Villalobos, “ Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis,” Journal of Clinical Virology. 2020 May 21:104455.

W. Yang, F. Yan, “Patients with RT-PCR-confirmed COVID-19 and normal chest CT,” Radiology. 2020 May;295(2):E3.

Y.H. Jin, L. Cai, ZS. Cheng, H. Cheng, T. Deng, YP. Fan, C. Fang, D. Huang, LQ. Huang, Q Huang, Y Han, “ A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia” Military Medical Research. 2020 Dec 1;7(1):4.

B. Udugama, P. Kadhiresan, HN. Kozlowski, A. Malekjahani, M. Osborne, Li VYC, H Chen, S Mubareka, JB Gubbay, WCW Chan, “Diagnosing COVID-19: The Disease and Tools for Detection,” ACS Nano. 2020 Apr 28;14(4):3822-3835. doi: 10.1021/acsnano.0c02624. Epub 2020 Mar 30. PMID: 32223179; PMCID: PMC7144809.

K. Green, A. Winter, R. Dickinson, S. Graziadio, R. Wolff, S. Mallett, AJ Allen, “

What tests could potentially be used for the screening, diagnosis and monitoring of COVID-19 and what are their advantages and disadvantages,” The Centre for Evidence Based Medicine (CEBM) https://www. cebm. net/covid-19/what-testscould-potentially-be-used-for-the-screening-diagnosis-and-monitoringof-covid-19-and-what-are-their-advantages-and-disadvantages. 2020.

RP. Oda,MA. Strausbauch, AF. Huhmer, et al. “Infrared-mediated thermocycling for ultrafast polymerase chain reaction amplification of DNA,” Anal Chem. 1998; 70(20):4361-4368. doi:10.1021/ac980452i

A. Chien, DB. Edgar, JM. Trela, “Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus,” J Bacteriol. 1976;127(3):1550-1557. doi:10.1128/JB.127.3.1550-1557.1976

C. Fermér, P. Nilsson,M. Larhed, “Microwave-assisted high-speed PCR,” European journal of pharmaceutical sciences. 2003 Feb 1;18(2):129-32.

PH. Van den Boogert, MP. van Gent-Pelzer, PJ. Bonants, SH. De Boer, JG Wander, CA Lévesque, GC Van Leeuwen, Baayen RP. “Development of PCR-based detection methods for the quarantine phytopathogen Synchytrium endobioticum, causal agent of potato wart disease,” European Journal of Plant Pathology. 2005 Sep 1; 113(1):47-57.

N. Boonham, LG. Pérez, MS. Mendez, EL. Peralta, A. Blockley, K. Walsh, I. Barker, RA. Mumford, “Development of a real-time RT-PCR assay for the detection of Potato spindle tuber viroid” Journal of virological methods. 2004 Mar 15; 116(2):139-46.

PW. Tooley, FN. Martin, MM. Carras, RD. Frederick, “Real-time fluorescent polymerase chain reaction detection of Phytophthora ramorum and Phytophthora pseudosyringae using mitochondrial gene regions,” Phytopathology. 2006 Apr; 96(4):336-45.

PA. Auroux, Y. Zoc, A. DeMello, A. Manz, PJ. Day, “Miniaturised nucleic acid analysis,” Lab on a Chip. 2004; 4(6):534-46.

MG. Roper, CJ. Easley, JP. Landers, “Advances in polymerase chain reaction on microfluidic chips,” Analytical chemistry. 2005 Jun 15; 77(12):3887-94.

J. Xiaoyu, N. Zhiqiang, C. Wenyuan, Z. Weiping, “Polydimethylsiloxane (PDMS)-based spiral channel PCR chip,” Electronics Letters. 2005 Aug 4; 41(16):890-1.

M. Yang, R. Pal, MA. Burns, “Cost-effective thermal isolation techniques for use on microfabricated DNA amplification and analysis devices,” Journal of Micromechanics and Microengineering. 2004 Oct 29;15(1):221.

Hu G, Xiang Q, Fu R, Xu B, Venditti R, Li D. Electrokinetically controlled real-time polymerase chain reaction in microchannel using Joule heating effect. Analytica Chimica Acta. 2006 Jan 31;557(1-2):146-51.

ZQ. Niu, WY. Chen, SY. Shao, XY. Jia, WP. Zhang, “DNA amplification on a PDMS–glass hybrid microchip,” Journal of micromechanics and microengineering. 2006 Jan 19;16(2):425.

C. Zhang, J. Xu, J. Wang, H. Wang, “Continuous‐flow polymerase chain reaction microfluidics by using spiral capillary channel embedded on copper,” Analytical letters. 2007 Feb 1; 40(3):497-511.

Z. Guttenberg, H. Müller, H. Habermüller, A. Geisbauer, J. Pipper, J. Felbel,M. Kielpinski, J Scriba, A Wixforth, “Planar chip device for PCR and hybridization with surface acoustic wave pump,” Lab on a Chip. 2005;5(3):308-17.

L. Kulhari, P K. Khanna, “Design, simulation and fabrication of LTCC-based microhotplate for gas sensor applications,” Microsyst Technol. 2018; 24: 2169–2175.

L. Kulhari, A. Chandran, K. Ray, PK. Khanna, “Design, fabrication and characterization of LTCC micro-hotplates for gas-sensing application,” Microelectronics International. 2019 Nov 29.

L. Kulhari, S. Kumar, PK. Khanna, “Design and Fabrication of Micro-spiral for Specific Applications,” National Conference on Recent Trends in Microwave Techniques and Applications. 2012.

L. Kulhari, K. Ray, N. Suri, PK. Khanna, “Detection and characterization of CO gas using LTCC micro-hotplates,” Sādhanā. 2020 Dec; 45(1):1-6.

MA. Northrup, “DNA amplification with a microfabricated reaction chamber,” Technical Digest of 7th Intl. Conf. on Solid-State Sensors and Actuators (1993); 924-926.

L. Kulhari, K. Ray,A. Paptan,N. Suri, PK. Khanna, “Development of LTCC micro‐hotplate with PTC temperature sensor for gas‐sensing applications,” International Journal of Applied Ceramic Technology. 2020 May; 17(3):1430-9.

M.Z . Iskandarani., “Detection of Unwanted Odors using Unmasking Odor Algorithm (UOA)” structure, 20, p.21.

MS Joarder, L Kulhari, BH Ahmad, K Ray. “MOX based E-nose for non-invasive biomedical applications. Przegląd Elektrotechniczny” 2021;97.

K. Malecha, I. Gancarz, LJ. Golonka, “A PDMS/LTCC bonding technique for microfluidic application,” Journal of Micromechanics and Microengineering. 2009 Sep 17;19(10):105016.

K. Malecha, “A PDMS–LTCC bonding using atmospheric pressure plasma for microsystem applications,” Sensors and Actuators B: Chemical. 2013 May 1; 181:486-93.




How to Cite

Kulhari, L. ., Suri, N. ., Ahmad, B. H. ., Yupapin, P. ., & Ray, K. . (2022). Thermal Performance Simulation of an LTCC Micro-Reactor for RT-PCR in Detection of SARS-Cov-2 Detection. Journal of Telecommunication, Electronic and Computer Engineering (JTEC), 14(3), 29–34. Retrieved from

Most read articles by the same author(s)