This study investigates various microfluidic chip fabrication techniques, highlighting their applicability and limitations in the context of urgent diagnostic needs showcased by the COVID-19 pandemic. Through a detailed examination of methods such as computer numerical control milling of a polymethyl methacrylate, soft lithography for polydimethylsiloxane-based devices, xurography for glass-glass chips, and micromachining-based silicon-glass chips, we analyze each technique's strengths and trade-offs. Hence, we discuss the fabrication complexity and chip thermal properties, such as heating and cooling rates, which are essential features of chip utilization for a polymerase chain reaction. Our comparative analysis reveals critical insights into material challenges, design flexibility, and cost-efficiency, aiming to guide the development of robust and reliable microfluidic devices for healthcare and research. This work underscores the importance of selecting appropriate fabrication methods to optimize device functionality, durability, and production efficiency.

Department of Chemistry and Biochemistry Mendel University in Brno Zemědělská 1 Brno 613 00 Czech Republic

Department of Microelectronics Faculty of Electrical Engineering and Communication Brno University of Technology Technická 3058 10 Brno 616 00 Czech Republic

Ministry of Education Key Laboratory of Micro and Nano Systems for Aerospace School of Mechanical Engineering Northwestern Polytechnical University 127 West Youyi Road Xi'an 710072 Shaanxi People's Republic of China

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Whitesides, G. M. The origins and the future of microfluidics. nature 442, 368–373 (2006). PubMed

Sackmann, E. K., Fulton, A. L. & Beebe, D. J. The present and future role of microfluidics in biomedical research. Nature507, 181–189 (2014). PubMed

Zhang, H. et al. Nanolithography toolbox—Simplifying the design complexity of microfluidic chips. J. Vacuum Sci. Technol. B Nanatechnol. Microelectronics: Mater. Process. Meas. Phenom.38, 063002 (2020).

Scott, S. M. & Ali, Z. Fabrication methods for microfluidic devices: An overview. Micromachines12, 319 (2021). PubMed PMC

Velten, T. et al. Roll-to-roll hot embossing of microstructures. Microsyst. Technol.17, 619–627 (2011).

Weisgrab, G., Ovsianikov, A. & Costa, P. F. Functional 3D printing for microfluidic chips. Adv. Mater. Technol.4, 1900275 (2019).

Suriano, R. et al. Femtosecond laser ablation of polymeric substrates for the fabrication of microfluidic channels. Appl. Surf. Sci.257, 6243–6250 (2011).

Thomas, L. E. et al. A glucose meter accuracy and precision comparison: The freestyle flash versus the accu-chek advantage, accu-chek compact plus, ascensia contour, and the BD logic. Diabetes. Technol. Ther.10, 102–110 (2008). PubMed

Ryan, F., O’SHEA, S. & Byrne, S. The reliability of point-of‐care prothrombin time testing. A comparison of CoaguChek S® and XS® INR measurements with hospital laboratory monitoring. Int. J. Lab. Hematol.32, e26–e33 (2010). PubMed

Carrilho, E., Martinez, A. W. & Whitesides, G. M. Understanding wax printing: A simple micropatterning process for paper-based microfluidics. Anal. Chem.81, 7091–7095 (2009). PubMed

Madhankumar, P., Sujatha, L., Sundar, R. & Viswanadam, G. Fabrication of low-cost MEMS microfluidic devices using metal embossing technique on glass for lab-on-chip applications. J. Micromech. Microeng.33, 084001 (2023).

Metz, S., Holzer, R. & Renaud, P. Polyimide-based microfluidic devices. Lab. Chip. 1, 29–34 (2001). PubMed

Fan, Y., Li, H., Yi, Y. & Foulds, I. G. PMMA to polystyrene bonding for polymer based microfluidic systems. Microsyst. Technol.20, 59–64 (2014).

Lebedev, D. et al. Focused ion beam milling based formation of nanochannels in silicon-glass microfluidic chips for the study of ion transport. Microfluid. Nanofluid.25, 51 (2021).

Fornell, A., Söderbäck, P., Liu, Z., De Albuquerque Moreira, M. & Tenje, M. Fabrication of silicon microfluidic chips for acoustic particle focusing using direct laser writing. Micromachines11, 113 (2020). PubMed PMC

Borók, A., Laboda, K. & Bonyár, A. PDMS bonding technologies for microfluidic applications: A review. Biosensors11, 292 (2021). PubMed PMC

Nge, P. N., Rogers, C. I. & Woolley, A. T. advances in microfluidic materials, functions, integration, and applications. Chem. Rev.113, 2550–2583 (2013). PubMed PMC

Kurita, R. & Niwa, O. Microfluidic platforms for DNA methylation analysis. Lab. Chip. 16, 3631–3644 (2016). PubMed

Zhuang, J., Yin, J., Lv, S., Wang, B. & Mu, Y. Advanced lab-on-a-chip to detect viruses–current challenges and future perspectives. Biosens. Bioelectron.163, 112291 (2020). PubMed PMC

Zeng, W., Jacobi, I., Beck, D. J., Li, S. & Stone, H. A. Characterization of syringe-pump-driven induced pressure fluctuations in elastic microchannels. Lab. Chip. 15, 1110–1115 (2015). PubMed

Peng, R. & Li, D. Electrokinetic motion of single nanoparticles in single PDMS nanochannels. Microfluid. Nanofluid.21, 1–10 (2017).

Isiksacan, Z., Guler, M. T., Aydogdu, B., Bilican, I. & Elbuken, C. Rapid fabrication of microfluidic PDMS devices from reusable PDMS molds using laser ablation. J. Micromech. Microeng.26, 035008 (2016).

Chu, M., Nguyen, T., Lee, E., Morival, J. & Khine, M. Plasma free reversible and irreversible microfluidic bonding. Lab. Chip. 17, 267–273 (2017). PubMed PMC

Songjaroen, T., Dungchai, W., Chailapakul, O., Henry, C. S. & Laiwattanapaisal, W. Blood separation on microfluidic paper-based analytical devices. Lab. Chip. 12, 3392–3398 (2012). PubMed

Ramdzan, A. N., Almeida, M. I. G., McCullough, M. J. & Kolev, S. D. Development of a microfluidic paper-based analytical device for the determination of salivary aldehydes. Anal. Chim. Acta. 919, 47–54 (2016). PubMed

Yamada, K., Shibata, H., Suzuki, K. & Citterio, D. Toward practical application of paper-based microfluidics for medical diagnostics: State-of-the-art and challenges. Lab. Chip. 17, 1206–1249 (2017). PubMed

Torul, H. et al. Paper membrane-based SERS platform for the determination of glucose in blood samples. Anal. Bioanal. Chem.407, 8243–8251 (2015). PubMed

Lin, Y. et al. Detection of heavy metal by paper-based microfluidics. Biosens. Bioelectron.83, 256–266 (2016). PubMed

Neuville, A. et al. Xurography for microfluidics on a reactive solid. Lab. Chip. 17, 293–303 (2017). PubMed

Lei, K. F., Chang, C. H. & Chen, M. J. Paper/PMMA hybrid 3D cell culture microfluidic platform for the study of cellular crosstalk. ACS Appl. Mater. Interfaces. 9, 13092–13101 (2017). PubMed

Fan, Y., Liu, Y., Li, H. & Foulds, I. G. Printed wax masks for 254 nm deep-UV pattering of PMMA-based microfluidics. J. Micromech. Microeng.22, 027001 (2012).

Nayak, N. C., Yue, C., Lam, Y. & Tan, Y. Thermal bonding of PMMA: Effect of polymer molecular weight. Microsyst. Technol.16, 487–491 (2010).

Sun, A. et al. An integrated microfluidic platform for nucleic acid testing. Microsystems Nanoengineering. 10, 66 (2024). PubMed PMC

Liu, X. et al. Smartphone integrated handheld (SPEED) digital polymerase chain reaction device. Biosens. Bioelectron.232, 115319 (2023). PubMed

Zhang, H. et al. SPEED: An integrated, smartphone-operated, handheld digital PCR device for point-of-care testing. Microsystems Nanoengineering. 10, 62 (2024). PubMed PMC

Girdwood, S. et al. The integration of tuberculosis and HIV testing on GeneXpert can substantially improve access and same-day diagnosis and benefit tuberculosis programmes: A diagnostic network optimization analysis in Zambia. PLOS Global Public. Health. 3, e0001179 (2023). PubMed PMC

Li, J. et al. Point-of-care testing of SARS-CoV-2 variants identified by XNA-Based RT-qPCR. Archives Microbiol. Immunol.7, 487–497 (2023).

Zhang, W. et al. PMMA/PDMS valves and pumps for disposable microfluidics. Lab. Chip. 9, 3088–3094 (2009). PubMed

Fan, Y. Low-cost microfluidics: Materials and methods. Micro Nano Lett.13, 1367–1372 (2018).

TESA. tesa® 61395, https://www.tesa.com/en/industry/tesa-61395.html

Chen, C. S., Chen, S. C., Liao, W. H., Chien, R. D. & Lin, S. H. Micro injection molding of a micro-fluidic platform. Int. Commun. Heat Mass Transfer. 37, 1290–1294 (2010).

Li, J. et al. Hot embossing/bonding of a poly (ethylene terephthalate)(PET) microfluidic chip. J. Micromech. Microeng.18, 015008 (2007).

Xia, Y. & Whitesides, G. M. Soft lithography. Angew. Chem. Int. Ed.37, 550–575 (1998). PubMed

Iliescu, C., Poenar, D. P., Carp, M. & Loe, F. C. A microfluidic device for impedance spectroscopy analysis of biological samples. Sens. Actuators B. 123, 168–176 (2007).

Liu, X., Zhu, H., Sabó, J., Lánský, Z. & Neužil, P. Improvement of the signal to noise ratio for fluorescent imaging in microfluidic chips. Sci. Rep.12, 18911 (2022). PubMed PMC

Gao, D., Liu, H., Jiang, Y. & Lin, J. M. Recent advances in microfluidics combined with mass spectrometry: Technologies and applications. Lab. Chip. 13, 3309–3322 (2013). PubMed

Hu, X. et al. Fabrication of polyimide microfluidic devices by laser ablation based additive manufacturing. Microsyst. Technol.26, 1573–1583 (2020).

Riester, O., Laufer, S. & Deigner, H. P. Direct 3D printed biocompatible microfluidics: Assessment of human mesenchymal stem cell differentiation and cytotoxic drug screening in a dynamic culture system. J. Nanobiotechnol.20, 540 (2022). PubMed PMC

Balram, K. C. et al. The nanolithography toolbox. J. Res. Natl. Inst. Stand. Technol.121, 464 (2016). PubMed PMC

Al-Adhami, M., Andar, A., Tan, E., Rao, G. & Kostov, Y. A solvent-based method to fabricate PMMA microfluidic devices. Lab. Chip (2017).

Swaggard, T. et al. The name is bond – heat bond: Using a heated lamination press for thermoplastic thin film bonding. Lab Chip (2022).

Zhu, H. et al. Heat transfer time determination based on DNA melting curve analysis. Microfluid. Nanofluid.24, 1–8 (2020).

Neuzil, P., Cheng, F., Soon, J. B. W., Qian, L. L. & Reboud, J. Non-contact fluorescent bleaching-independent method for temperature measurement in microfluidic systems based on DNA melting curves. Lab. chip. 10, 2818–2821 (2010). PubMed

Neužil, P., Sun, W., Karásek, T. & Manz, A. Nanoliter-sized overheated reactor. Appl. Phys. Lett.106 (2015).

Prasad, A. et al. Thermal conductivity measurement of Soda–Lime–silica glass by transient 3 ω method with au Thin Film-based Micro-heater/Temperature Sensor fabricated by an innovative Approach. Int. J. Thermophys.41, 100 (2020).

Yamasue, E., Susa, M., Fukuyama, H. & Nagata, K. Thermal conductivities of silicon and germanium in solid and liquid states measured by non-stationary hot wire method with silica coated probe. J. Cryst. Growth.234, 121–131 (2002).

Assael, M., Botsios, S., Gialou, K. & Metaxa, I. Thermal conductivity of polymethyl methacrylate (PMMA) and borosilicate crown glass BK7. Int. J. Thermophys.26, 1595–1605 (2005).

Wei, J. et al. Enhanced thermal conductivity of polydimethylsiloxane composites with carbon fiber. Compos. Commun.17, 141–146 (2020).

Zhang, H. et al. Revealing the secrets of PCR. Sens. Actuators B. 298, 126924 (2019).

Piruska, A. et al. The autofluorescence of plastic materials and chips measured under laser irradiation. Lab. Chip. 5, 1348–1354 (2005). PubMed

Sasaki, H., Onoe, H., Osaki, T., Kawano, R. & Takeuchi, S. Parylene-coating in PDMS microfluidic channels prevents the absorption of fluorescent dyes. Sens. Actuators B. 150, 478–482 (2010).