Vibhav
Shukla
and
Kafeel Ahmad
Siddiqui
*
Department of Chemistry, National Institute of Technology Raipur, GE Road Raipur, 492010, Chhattisgarh, India. E-mail: kasiddiqui.chy@nitrr.ac.in
First published on 28th May 2025
The integration of metal–organic frameworks (MOFs) into biomedical diagnostics offers a promising approach to enhancing sensitivity, selectivity, and sustainability in test strip technology. MOFs, with their high porosity, tunable functionality, and exceptional luminescent properties, provide an innovative platform for developing next-generation biosensors. Their ability to interact with specific biomarkers enables highly accurate and rapid detection of health-related analytes, such as glucose, in real urine samples. Additionally, the catalytic properties of MOFs enhance degradation mechanisms, making them suitable for environmental applications like wastewater treatment. This highlight examines how MOFs and their derived composites are reshaping the design and functionality of biomedical test strips, offering a glimpse into a more efficient and eco-conscious future in diagnostics. By leveraging their multifunctionality, MOFs can improve the sensitivity of diagnostic platforms while reducing reliance on conventional materials, aligning with the growing demand for greener and more effective healthcare solutions.
Metal–organic frameworks (MOFs), composed of metal ions or clusters and organic ligands, feature highly porous structures that allow precise control over size, shape, surface area, porosity, and chemical properties (Scheme 1).4 These characteristics make MOFs highly suitable for biomedical test strips, as they provide improved sensitivity, rapid detection, and eco-friendly advantages.4 Despite the widespread use of diagnostic strips, there exists a clear market gap in delivering portable, eco-friendly, and highly sensitive diagnostic tools suitable for real-world conditions, especially in resource-constrained environments. Existing enzyme-based test strips often suffer from limited analyte specificity, poor long-term stability, and environmental concerns related to chemical waste and disposable plastic substrates.5 Their tunable frameworks enable the synthesis of 1D, 2D, and 3D structures, making them highly versatile for biomedical applications. MOFs are commonly integrated into the sensing elements of test strips to enhance analyte detection using optical, electrochemical, or colorimetric signals.6
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Scheme 1 (a) Schematic representation of MOF and composite synthesis, illustrating the stepwise formation process along with examples of (b) 1D, (c) 2D, and (d) 3D MOFs. |
Traditional test strips rely on straightforward chemical reactions that produce a visual or colorimetric response. While these methods are cost-effective and user-friendly, they face several drawbacks, including:
• Low sensitivity: detecting trace amounts of analytes remains challenging with traditional methods.
• Environmental concerns: many conventional test strips contain toxic substances or pose disposal issues.
• Design challenges: developing test strips capable of detecting a wide range of analytes with high precision and sensitivity is a complex engineering task.
To address these challenges, recent advancements in colorimetric biosensing have introduced a highly efficient and rapid detection method. Unlike conventional peroxide-based colorimetric assays, which require hydrogen peroxide and oxygen, this novel approach utilizes a single-step enzyme reaction, where an oxidoreductase enzyme transfers electrons to a coloring reagent via a metal complex mediator. This technique significantly enhances detection speed (within ~5 seconds) and accuracy, eliminating oxygen dependency and reducing measurement inconsistencies. The integration of MOFs with such next-generation colorimetric sensors further strengthens the sensitivity and stability of test strips. MOF-based systems offer high selectivity, enabling the detection of low analyte concentrations with exceptional precision.7 Additionally, by incorporating iron, ruthenium, osmium, and copper complexes as mediators, the new method ensures enhanced signal output and cost-effectiveness. Thus, the synergistic combination of MOFs and advanced colorimetric techniques presents a transformative approach in biomedical diagnostics, paving the way for highly sensitive, rapid, and sustainable test strip technologies.8
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Fig. 1 Schematic illustration of MOF synthesis using organic linkers and metal ions, followed by its application as a detector for glucose sensing in urine constituents. |
Beyond glucose detection, MOF-based test strips have also been successfully employed for the colorimetric detection of trichloroacetic acid (TCA), a carcinogenic metabolite in human urine. A fluorescein-functionalized Zn-based MOF (FS@Zn-MOF-2) was designed as a microporous luminescent probe, offering a rapid response time of less than 30 seconds and a detection limit of 1.22 ppm. The portable paper-based FS@Zn-MOF-2 strip displayed a distinct fluorescence change upon exposure to TCA, providing an efficient, selective, and user-friendly approach for monitoring TCE exposure.12 The performance metrics of selected MOF-based test strips in real samples are summarized in Table 1.
S. no | Feature | MOFs | MXenes | Borophene | Ref. |
---|---|---|---|---|---|
1 | Conductivity | Moderate | High | Very high | 13, 14 |
2 | Stability | High (with modification) | Low (oxidation prone) | Very low (unstable in ambient) | 15, 16 |
3 | Surface functionalization | Easy | Moderate | Difficult | 17, 18 |
4 | Eco-friendliness | High | Moderate | Low | 19, 20 |
5 | Biosensing versatility | High | Medium | Medium | 21, 22 |
Additionally, MOF-based test strips have been developed for uric acid detection, which is crucial for diagnosing hyperuricemia and related metabolic disorders. A phosphonate MOF composite (Cu2+@MIL-91(Al:Eu)) exhibited an “off–on” fluorescence mechanism upon interaction with uric acid, achieving a detection limit as low as 1.6 μM. The MOF-integrated test strip demonstrated high selectivity in real urine samples, enabling rapid, cost-effective, and accurate diagnosis of abnormal uric acid levels.23
Beyond laboratory demonstrations, MOF-based biosensors have also shown practical applicability in real clinical and environmental scenarios.24 For instance, Fe@Zinc-MOF-2 integrated test strips have been successfully applied to detect glucose concentrations directly from human urine samples, demonstrating high selectivity and rapid response times. In infectious disease diagnostics, MOF-derived fluorescent sensors have been used for the detection of SARS-CoV-2 RNA during the COVID-19 pandemic, showcasing high sensitivity and short assay times suitable for point-of-care testing.25 Similarly, FS@Zn-MOF-based portable strips have efficiently detected trichloroacetic acid (TCA), a carcinogenic environmental metabolite, in real urine samples, enabling early exposure monitoring in occupational settings. Additionally, phosphonate MOF composites such as Cu2+@MIL-91(Al:Eu) have enabled uric acid quantification in real clinical samples, facilitating the diagnosis of hyperuricemia and related metabolic disorders. These case studies underscore the translational potential of MOF-based biosensors, moving beyond proof-of-concept experiments toward practical healthcare and environmental monitoring solutions.
MOFs offer several advantages that can overcome the limitations of traditional test strips:
• Increased detection efficiency: MOFs can be tailored to selectively interact with target analytes, enhancing the ability to detect even trace amounts with exceptional precision.26
• Environmentally friendly fabrication: MOFs are often created through sustainable processes that minimize the environmental footprint of production.27
• Multi-analyte detection: MOFs' flexibility allows for the design of test strips that can simultaneously identify several different analytes, enhancing diagnostic efficiency.28
Since MOFs can be made from readily available, inexpensive materials, they help reduce the environmental impact and cost of producing test strips. The development of Fe@Zinc-MOF-2, FS@Zn-MOF, and Cu2+@MIL-91(Al:Eu)-based test strips highlights the transformative role of MOF composites in next-generation biomedical diagnostics, paving the way for more sensitive, reliable, and eco-friendly healthcare solutions.
Furthermore, in the context of 5th generation biosensors—such as wearable devices, breath-based diagnostics, and integrated AI platforms—MOFs present unique advantages over MXenes and borophene.38,39 Although MXenes exhibit excellent electrical conductivity suitable for electrochemical biosensors and borophene offers exceptional mechanical strength, their widespread application is hindered by issues like environmental instability, oxidative degradation, and difficulties in surface functionalization.40 Breath-based diagnostics, for instance, demand materials that can operate reliably in humid and complex biological environments. MOFs, with their superior chemical tunability, high porosity, and intrinsic luminescent properties, enable selective and sensitive detection of volatile biomarkers such as nitric oxide, acetone, and ammonia in exhaled breath.41 Additionally, MOFs can be engineered to exhibit dual functionalities (e.g., optical and electrochemical responsiveness), crucial for the development of multifunctional “nose-on-chip” devices.42
Recent advances have demonstrated that MOF-based chips can detect trace biomarkers in breath with high sensitivity and stability, making them ideal candidates for next-generation wearable diagnostics and portable breath analysers. While MXenes and borophene show promise, the modular architecture of MOFs allows for precise pore tailoring and surface chemistry adaptation, providing a more versatile and biocompatible platform for integrated biosensing applications. Therefore, our focused emphasis on MOF chips stems from their superior versatility, environmental stability, multifunctionality, and proven translational potential in real-world 5th-generation diagnostic technologies. A comparative summary of various MOF-based biosensing systems, their performance parameters, and real-sample applicability is presented in Table 2, illustrating the practical potential and versatility of MOF-integrated diagnostics.
MOF-based system | Target analyte | Detection method | Detection limit | Response time | Real sample used | Ref. |
---|---|---|---|---|---|---|
Fe@Zn-MOF-2 | Glucose | Fluorescence quenching | 0.846 ppm | ~5 sec | Human urine | 11 |
FS@Zn-MOF | Trichloro acetic acid (TCA) | Colorimetric (fluorescein) | 1.22 ppm | <30 sec | Urine (occupational) | 43 |
Cu2+@MIL-91(Al:Eu) | Uric acid | “Off–on” fluorescence | 1.6 μM | Fast | Clinical urine | 44 |
Zr-MOF@GO | Dopamine | Electrochemical | 50 nM | Seconds | Serum | 19 |
Co-MOF/AuNPs | Glucose | Enzyme-free electrochemical | 0.16 μM | Few sec | Saliva | 45 |
Tb-MOF/quantum dots | Glucose | Fluorescence ratiometric | 10 nM | <1 min | Buffer | 19 |
MOF-74(Ni)/CNT | H2O2 (indirect glucose) | Amperometric | 1.2 μM | Fast | Serum | 45 |
Eu-MOF | SARS-CoV-2 RNA | Fluorescence (hybridization) | 87 copies per mL | ∼20 min | Nasopharyngeal swab | 19 |
MIL-101(Fe)/aptamer | Aflatoxin B1 (food toxin) | Electrochemical | 0.09 ng mL−1 | Few min | Corn & peanut extract | 17 |
ZIF-8@PDA@PtNPs | Glucose | Colorimetric + catalytic | 1.1 μM | <5 min | Blood plasma | 45 |
• Infectious disease diagnostics: MOFs can be engineered to target specific pathogens or biomarkers linked to diseases like malaria, tuberculosis, or COVID-19. By incorporating MOFs with customized binding sites, test strips can deliver quicker, more accurate results for disease detection.
• Disease biomarker identification: MOFs can be designed to selectively bind disease biomarkers, enabling test strips to detect low concentrations of specific proteins or genetic material, improving diagnostic sensitivity.
• Heavy metal detection: MOFs can be tailored to identify trace amounts of heavy metals in biological fluids, providing an efficient and sensitive alternative to traditional chemical detection methods.
Glucose monitoring plays a vital role in managing diabetes and other metabolic disorders.46 Unlike conventional enzyme-based glucose test strips, which suffer from stability issues and limited sensitivity, MOF-based alternatives provide higher selectivity and durability (Fig. 2). The direct electron transfer properties of MOFs eliminate the need for enzymatic components, making them more reliable for long-term use. Traditional enzyme-based glucose sensors, which primarily depend on glucose oxidase, often face stability issues due to enzyme degradation. In contrast, MOF-based glucose sensors provide enzyme-free, highly sensitive, and selective detection methods.47 These sensors, when combined with conductive materials such as carbon nanomaterials, metal nanoparticles, and metal oxides, have demonstrated excellent performance in electrochemical glucose detection. Among them, copper-based MOFs are widely used due to their strong redox activity, and their combination with gold nanoparticles enhances electron transfer efficiency, leading to improved glucose sensing in biological samples. Similarly, cobalt-based MOFs exhibit peroxidase-like activity, allowing for enzyme-free glucose detection through oxidation reactions. Researchers have also developed MOF-based glucose sensors anchored on nanomaterials like graphene oxide, which offer high sensitivity and selectivity for detecting glucose in different biological fluids.48
Apart from electrochemical detection, luminescent MOFs have been utilized for fluorescence-based glucose sensing. Certain lanthanide-based MOFs exhibit fluorescence changes upon interaction with glucose, enabling a rapid and label-free sensing approach.49 Other MOFs, integrated with quantum dots, have demonstrated ultra-sensitive glucose detection, reaching nanomolar detection limits. In addition, colorimetric glucose sensors based on MOFs mimic natural enzyme activity, producing visible colour changes when reacting with glucose. This allows for simple and effective glucose detection without requiring complex instrumentation.
Beyond glucose monitoring, MOFs have been extensively explored for identifying disease biomarkers, which is crucial for early disease detection and prognosis. These materials have been functionalized with various biological recognition elements, such as antibodies, aptamers, and DNA probes, to detect biomarkers associated with different diseases.50 For instance, MOF-based biosensors have been used for detecting cancer biomarkers at extremely low concentrations, making them promising tools for early cancer diagnosis. Some MOF sensors have also been developed for detecting microRNAs linked to certain cancers, offering high selectivity and efficiency in diagnostic applications. MOFs have further shown potential in diagnosing bacterial and viral infections by detecting specific proteins or nucleic acids. During the COVID-19 pandemic, MOF-based fluorescence sensors were employed for the rapid detection of viral RNA, demonstrating high sensitivity. Additionally, electrochemical MOF-based immunosensors have been developed for detecting tuberculosis biomarkers, offering accurate and reliable results.
In neurodegenerative disease diagnostics, MOFs have been applied to detect biomarkers related to conditions such as Alzheimer's and Parkinson's diseases. Some MOF-based sensors have been designed to detect amyloid-β aggregates, which are linked to Alzheimer's, enabling early-stage diagnosis. Similarly, MOF-based biosensors have been used for dopamine detection, playing a significant role in diagnosing Parkinson's disease by providing rapid and selective detection. MOF-based biosensors are transforming the landscape of biomedical diagnostics by offering high sensitivity, selectivity, and rapid detection capabilities. Their adaptability to various detection techniques, including electrochemical, fluorescence, and colorimetric methods, makes them highly promising for next-generation healthcare applications. Ongoing research continues to focus on enhancing their stability, scalability, and real-world clinical applicability, ensuring their integration into practical diagnostic tools in the near future.
From an economic perspective, MOF-based test strips offer significant cost advantages. The raw materials used to synthesize MOFs are often abundant and inexpensive, and the scalable nature of MOF production further reduces manufacturing costs. Additionally, the cost-effective synthesis of MOFs supports scalable production, making these test strips accessible for large-scale healthcare applications (Fig. 3). Their long lifespan and reusability further contribute to cost savings and reduced medical waste. This economic efficiency has the potential to make diagnostic tools more affordable, particularly in resource-limited regions, thereby enhancing access to essential healthcare services. Additionally, the long lifespan and reusability of MOFs may decrease the need for frequent replacement of diagnostic equipment, leading to cost savings over time.
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Fig. 3 Sustainability aspects of MOF-based test strips, emphasizing their eco-friendly and efficient characteristics. |
• Sustainable production: MOFs' ability to be synthesized from renewable materials supports the shift toward a circular economy, reducing the overall environmental footprint of the healthcare industry.
• Scalable manufacturing: the ease with which MOFs can be produced at scale may enable rapid deployment of affordable, high-quality diagnostic tools worldwide, helping bridge gaps in healthcare accessibility.
In summary, MOFs not only offer a more environmentally sustainable approach to diagnostic technology but also present an opportunity for reducing costs and improving healthcare access, particularly in underserved communities.
• Stability under real-world conditions: MOFs can be sensitive to environmental factors such as humidity, temperature fluctuations, and exposure to air, which can lead to structural degradation over time. In biomedical applications, test strips must maintain their functionality across diverse climates, including high-humidity regions where moisture absorption could alter the MOF's properties. Researchers are actively working on developing more robust MOFs with enhanced water stability by modifying their organic linkers, incorporating hydrophobic coatings, or designing hybrid composite materials to improve durability in real-world conditions.
• Regulatory and safety concerns: the introduction of any new medical diagnostic technology requires extensive validation, regulatory approvals, and clinical trials to ensure safety and efficacy. Regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require rigorous testing before MOF-based biosensors can be integrated into mainstream healthcare. MOFs containing metal ions raise concerns about biocompatibility and potential toxicity, necessitating further studies to assess their long-term effects on human health. Developing bio-safe, non-toxic MOF formulations and demonstrating their reliability in real-world clinical studies will be key to gaining regulatory approval.
• Reproducibility and standardization: the performance of MOF-based test strips can vary due to differences in synthesis conditions, batch-to-batch inconsistencies, and challenges in quality control. Unlike traditional enzyme-based biosensors, which have well-defined production parameters, MOFs' diverse structural possibilities introduce complexities in ensuring uniformity across large-scale production. Establishing standardized fabrication protocols and improving quality control mechanisms are essential to overcoming this challenge.
Large-scale deployment of MOF-based test strips requires the establishment of affordable manufacturing pipelines, education of healthcare providers, and public engagement campaigns to build awareness about the advantages of these new technologies. Interdisciplinary collaboration between material scientists, healthcare professionals, social scientists, and communication experts will be essential to promote user adoption and societal acceptance. From a research standpoint, there remains a significant gap in transitioning MOF-based sensing systems from laboratory prototypes to clinically viable, scalable test strips. Most published work focuses on fundamental sensor development without demonstrating applicability in real-world samples or addressing regulatory scalability.53 Our study bridges this gap by successfully applying Fe@Zn-MOF test strips for glucose detection in actual urine samples and by exploring fabrication compatibility with paper substrates for low-cost deployment.8
Initiatives such as using visual arts, community outreach programs, and policy advocacy, as demonstrated in interdisciplinary approaches to pandemics like monkeypox prevention, can serve as models for the promotion of MOF-based diagnostics. Future research should integrate socio-economic impact studies, market access strategies, and public health communication to ensure that the technological advancements in MOFs translate into real-world healthcare benefits globally.54
• Enhancing stability and durability: researchers are exploring ways to improve the water and thermal stability of MOFs by incorporating protective coatings, hydrophobic functional groups, and hybrid composites with polymers or metal nanoparticles. Future studies should aim to develop next-generation MOFs with increased resistance to environmental factors, ensuring their longevity in real-world diagnostic applications.
• Developing low-cost, scalable synthesis techniques: advancements in solvent-free mechanochemical synthesis, microwave-assisted fabrication, and 3D printing of MOF-based test strips could significantly reduce costs and enhance scalability. Sustainable synthesis approaches that eliminate toxic solvents and use renewable materials will also contribute to making MOFs more commercially feasible.
• Integration with smart and wearable technologies: the future of biomedical diagnostics lies in smart and wearable biosensors. MOF-based materials, when integrated with flexible electronics, smartphone-based readout systems, and AI-driven diagnostic platforms, could revolutionize real-time health monitoring. Research should focus on adapting MOFs for continuous, on-the-go monitoring in wearable sensor formats.
• Integration of MOFs with AI, wearable devices, and smartphone diagnostics: the next generation of healthcare diagnostics is expected to be highly personalized, real-time, and decentralized, driven by smart technologies. Artificial Intelligence (AI) can significantly enhance the performance of MOF-based biosensors by enabling automated pattern recognition, predictive diagnostics, and anomaly detection based on complex biosensing data.55 Machine learning algorithms can be trained to interpret subtle fluorescence, colorimetric, or electrochemical signals from MOF-based test strips, improving diagnostic accuracy and reducing human error. In addition to AI, wearable biosensors incorporating MOF composites offer promising solutions for continuous health monitoring. Flexible and stretchable electronics embedded with MOFs can detect biomarkers in sweat, saliva, or interstitial fluids, allowing for non-invasive and real-time monitoring of chronic diseases like diabetes and cardiovascular conditions. Wearable patches, wristbands, and even textiles functionalized with MOF-based sensors are emerging as potential platforms for next-generation diagnostics.
Furthermore, smartphone-based detection systems integrated with MOF test strips are gaining traction due to their portability, affordability, and ease of use. Smartphone cameras, combined with app-based analytical tools, can be employed to read color changes, fluorescence emissions, or electrochemical signals from MOF-enhanced strips, providing immediate diagnostic feedback even in resource-limited settings. This integration opens up the possibility of widespread adoption of point-of-care diagnostics, telemedicine support, and remote patient monitoring, ultimately contributing to more proactive and accessible healthcare management.
• Broadening biomedical and environmental applications: while MOFs have already demonstrated success in glucose sensing and disease biomarker detection, expanding their use in cancer diagnostics, hormone-level monitoring, early-stage infection detection, and environmental pollutant analysis can greatly enhance their impact. Additionally, MOF-based test strips could be employed for real-time monitoring of airborne toxins, food contaminants, and water quality to improve public health monitoring.
With these advancements, MOFs could pave the way for the next generation of diagnostic tools, making them more for a wide range of medical and environmental applications. By addressing the current challenges and leveraging innovative technologies, MOF-based test strips have the potential to transform healthcare diagnostics and contribute to more efficient, accurate, and sustainable point-of-care testing.
Looking ahead, MOF-based biosensors are expected to play a transformative role in the global diagnostics market, which is projected to surpass USD 45 billion by 2030, with significant growth in point-of-care and wearable diagnostics. Within the next 5–7 years, the integration of MOFs with AI-driven smartphone applications and flexible wearable platforms is anticipated to transition from laboratory prototypes to commercial healthcare products. Advances in real-time breath-based MOF sensors could lead to non-invasive disease diagnostics for respiratory disorders, metabolic syndromes, and even early cancer detection. Moreover, regulatory progress and the establishment of clinical testing pipelines may enable the first MOF-based diagnostic strips to enter the FDA approval process within the decade. These emerging trends suggest a clear trajectory where MOFs will underpin next-generation biosensing technologies tailored for personalized, on-demand, and decentralized healthcare.
As research continues to refine MOF synthesis, improve stability, and expand biomedical applications, the adoption of MOF-integrated technologies in diagnostics is expected to increase. However, addressing regulatory challenges and optimizing production efficiency will be crucial in facilitating their widespread implementation in the global market. Ultimately, MOFs hold immense promise for revolutionizing diagnostic capabilities, providing a cost-effective, sustainable, and highly sensitive approach to disease detection and monitoring. With continued advancements in material science and biomedical engineering, MOF-based diagnostics may pave the way for more personalized, portable, and real-time healthcare solutions. Collaborative efforts among researchers, clinicians, and industry stakeholders will be key to unlocking their full potential in revolutionizing global healthcare.
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