Recent Advancements in Metal-Organic Framework-Based Microfluidic Chips for Biomedical Applications

Abstract

The integration of metal-organic frameworks (MOFs) with microfluidic technologies has opened new frontiers in biomedical diagnostics and therapeutics. Microfluidic chips offer precise fluid control, low reagent use, and high-throughput capabilities features further enhanced by MOFs' ample surface area, adjustable porosity, and catalytic activity. Together, they form powerful lab-on-a-chip platforms for sensitive biosensing, drug delivery, tissue engineering, and microbial detection. This review highlights recent advances in MOF-based microfluidic systems, focusing on material innovations, fabrication methods, and diagnostic applications. Particular emphasis is placed on MOF nanozymes, which enhance biochemical reactions for multiplexed testing and rapid pathogen identification. Challenges such as stability, biocompatibility, and manufacturing scalability are addressed, along with emerging trends like responsive MOFs, AI-assisted design, and clinical translation strategies. By bridging MOF chemistry and microfluidic engineering, these systems hold great promise for next-generation biomedical technologies.

Keywords: MOF-based nanozymes; biomedical application; cell migration; microfabrication; microfluidic chips; point-of-care diagnostics.

Figure 1

Illustration of the biocomposite patterning process. A bare polypropylene (PP) membrane is first patterned with a PDA/PEI coating using a PDMS mold containing microchannels. Subsequently, ZIF-8 is co-precipitated with the enzymes glucose oxidase (GOx) and horseradish peroxidase (HRP) directly onto the PDA/PEI layer, enabling in situ growth of the ZIF-8/enzyme composite. Copyright 2019 ACS [27].

Figure 2

Schematically presentation of developed immunosensor. Copyright 2024 Scientific Reports [29].

Figure 3

Schematic representation of microfluidic biosensing for foodborne bacteria using Pt-PCN-224 as a peroxidase-like catalyst for signal amplification. Copyright 2023 ACS [33].

Figure 4

Schematic of FeTPt@CCM synthesis and its combined therapeutic functions. (a) Design of the bioinspired “Trojan Horse” nanocarrier. (b) FeTPt prepared via microfluidics and coated with cancer cell membrane (CCM). (c) After injection, FeTPt@CCM accumulates in tumors, where Pt(IV) is reduced to Pt(II) for chemotherapy, Fe³⁺ induces ferroptosis via GSH/H₂O₂ reactions, and TCPP generates ¹O₂ under 670 nm light for PDT. This system enables synergistic chemo-, ferroptosis, and photodynamic therapy. Copyright 2023 Advanced Science [48].

Figure 5

Evaluation of the in vivo anticancer efficacy of FeTPt@CCM. (a,b) Fluorescence imaging of tumor-bearing mice and excised organs/tumors following intravenous injection of FeTPt or FeTPt@CCM. (c) Overview of treatment schedule. (d,e) Tumor growth curves under various treatments. (f,g) Photographs and weights of tumors collected at study endpoint. (h) H&E, TUNEL, and Ki67 staining of tumor tissues (scale bar = 100 µm). (i) Body weight monitoring during treatment. Groups with (+) or without (−) irradiation; n = 6 per group. Data shown as mean ± SD; ** p < 0.01, *** p < 0.001 (“***” represents statistical significance). Copyright 2023 Advanced Science [48].

Figure 6

Assessment of cytotoxicity and uptake of miR-200c-3p@ZIF-8. (a,b) Hemolysis comparison of PEI 25K, ZIF-8, and miR-200c-3p@ZIF-8. (c) Live/dead staining of HUVEC cells after treatment. (d) Cell viability across concentrations of PEI 25K and ZIF-8. (e) Uptake analysis via flow cytometry. (f) Confocal imaging of CHON-001 cells treated with free and formulated miR-200c-3p. Copyright 2023 Frontiers [51].

Figure 7

Antimicrobial activity of PS@ZIF-8. (a) Schematic showing microbial disruption by PS@ZIF-8. (b) Viability of E. coli after treatment with RB, porphyrin, ZIF-8, RB@ZIF-8, and porphyrin@ZIF-8 under dark and light conditions. (c) ROS generation assessed via DCFDA in treated and untreated cells under both lighting conditions. (d) Nucleic acid leakage from E. coli following probe exposure under dark and LED light (*** p < 0.001). Copyright 2025 ACS [58].

Figure 8

Organ-on-a-chip devices constructed from glass (a,b) and PDMS (c,d). (a,c) Full views of each device. (b,d) Close-up of a single culture chamber and Laplace valves. Scale bars: 500 μm. Copyright 2019 Elsevier [75].

Figure 9

VOC sensors developed in this study. (a) Image of the QCM-based sensor coated with MOF/PDMS. (b) Schematic showing the fabrication process of the MOF/PDMS-coated sensor. Copyright 2024 ACS [87].

Figure 10

Diagram showing the process for creating MOF-integrated microrobots on silicon substrates. Copyright 2021 ACS [98].

Figure 11

Schematic of the artificial neural network (ANN)-assisted design and implementation of a dual-function system for sensing and supercapacitor applications. Copyright 2022 Elsevier [148].