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Benefits of miniaturized chromatography with various detection modes, such as increased sensitivity, chromatographic efficiency, and speed, were recognized nearly 50 years ago. Over the past two decades, this approach has experienced rapid growth, driven by the emergence of mass spectrometry applications serving -omics sciences and the need for analyzing minute volumes of precious samples with ever higher sensitivity. While nanoscale liquid chromatography (flow rates <1 µL/min) has gained widespread recognition in proteomics, the adoption of microscale setups (flow rates ranging from 1 to 100 µL/min) for low molecular weight compound applications, including metabolomics, has been surprisingly slow, despite the inherent advantages of the approach. Highly heterogeneous matrices and chemical structures accompanied by a relative lack of options for both selective sample preparation and user-friendly equipment are usually reported as major hindrances. To facilitate the wider implementation of microscale analyses, we present here a comprehensive tutorial encompassing important theoretical and practical considerations. We provide fundamental principles in micro-chromatography and guide the reader through the main elements of a microflow workflow, from LC pumps to ionization devices. Finally, based on both our literature overview and experience, illustrated by some in-house data, we highlight the critical importance of the ionization source design and its careful optimization to achieve significant sensitivity improvement.
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Detecting weakly adsorbing molecules via label-free surface-enhanced Raman scattering (SERS) has presented a significant challenge. To address this issue, we propose a novel approach for creating tricomponent SERS substrates using dual-rim nanorings (DRNs) made of Au, Ag, and CuO, each possessing distinct functionalities. Our method involves depositing different metals on Pt nanoring skeletons to obtain each nanoring with varying surface compositions while maintaining a similar size and shape. Next, the mixture of these nanorings is transferred into a monolayer assembly with homogeneous intermixing on a solid substrate. The surface of the CuO DRNs has dangling bonds (Cu2+) that facilitate the strong adsorption of carboxylates through the formation of chelating bonds, while the combination of Au and Ag DRNs significantly enhances the SERS signal intensity through a strong coupling effect. Notably, the tricomponent assemblies enable the successful SERS-based analysis of biomolecules such as amino acids, proteins, nucleobases, and nucleotides.
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Ouro , Nanopartículas Metálicas , Ouro/química , Análise Espectral Raman/métodos , Prata/química , Adsorção , Nanopartículas Metálicas/químicaRESUMO
Various applications related to glucose catalysis have led to the development of functional nanozymes with glucose oxidase (GOX)-like activity. However, the unsatisfactory catalytic activity of nanozymes is a major challenge for their practical applications due to their inefficient hydrogen and electron transfer. Herein, we present the synthesis of AuFe/polydopamine (PDA) superparticles that exhibit photothermal-enhanced GOX-like activity. Experimental investigations and theoretical calculations reveal that the glucose oxidation process catalyzed by AuFe/PDA follows an artificial-cofactor-mediated hydrogen atom transfer mechanism, which facilitates the generation of carbon-centered radical intermediates. Rather than depending on charged Au surfaces for thermodynamically unstable hydride transfer, Fe(III)-coordinated PDA with abundant amino and phenolic hydroxyl groups serves as cofactor mimics, facilitating both hydrogen atom and electron transfer in the catalytic process. Finally, leveraging the photothermal-enhanced GOX-like and catalase-like activities of AuFe/PDA, we establish a highly sensitive and accurate point-of-care testing blood glucose determination with exceptional anti-jamming capabilities.
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Glucose Oxidase , Ouro , Hidrogênio , Indóis , Polímeros , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Ouro/química , Hidrogênio/química , Transporte de Elétrons , Indóis/química , Polímeros/química , Glucose/química , Catálise , Oxirredução , Glicemia/análise , Ferro/química , HumanosRESUMO
As a typical biomarker, the expression of microRNA is closely related to the occurrence of cancer. However, in recent years, the detection methods have had some limitations in the research and application of microRNAs. In this paper, an autocatalytic platform was constructed through the combination of a nonlinear hybridization chain reaction and DNAzyme to achieve efficient detection of microRNA-21. Fluorescently labeled fuel probes can form branched nanostructures and new DNAzyme under the action of the target, and the newly formed DNAzyme can trigger a new round of reactions, resulting in enhanced fluorescence signals. This platform is a simple, efficient, fast, low-cost, and selective method for the detection of microRNA-21, which can detect microRNA-21 at concentrations as low as 0.004 nM and can distinguish sequence differences by single-base differences. In tissue samples from patients with liver cancer, the platform shows the same detection accuracy as real-time PCR but with better reproducibility. In addition, through the flexible design of the trigger chain, our method could be adapted to detect other nucleic acid biomarkers.
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Técnicas Biossensoriais , DNA Catalítico , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/análise , DNA Catalítico/química , Reprodutibilidade dos Testes , Limite de Detecção , Hibridização de Ácido Nucleico , Biomarcadores , Técnicas Biossensoriais/métodosRESUMO
Therapeutic messenger RNAs (mRNAs) have emerged as powerful tools in the treatment of complex diseases, especially for conditions that lack efficacious treatment. The successful application of this modality can be attributed to its ability to encode entire proteins. While the large nature of these molecules has supported their success as therapeutics, its extended size creates several analytical challenges. To further support therapeutic mRNA development and its deployment in clinical trials, appropriate methods to support their characterization must be developed. In this review, we describe current analytical methods that have been used in the characterization of RNA quality, identity, and integrity. Advantages and limitations from several analytical techniques ranging from gel electrophoresis to liquid chromatography-mass spectrometry and from shotgun sequencing to intact mass measurements are discussed. We comprehensively describe the application of analytical methods in the measurements of capping efficiency, poly A tail analysis, as well as their applicability in stability studies.
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An analytical method based on capillary electrophoresis (CE) using capacitively coupled contactless conductivity detection (C4 D) was developed and validated for fast, straightforward, and reliable determination of lactate in artificial and human sweat samples. The background electrolyte was composed of equimolar concentrations (10 mmol/L) of 2-(N-morpholino)ethanesulfonic acid and histidine, with 0.2 mmol/L of cetyltrimethylammonium bromide as electroosmotic flow inverter. The limit of detection and quantification were 3.1 and 10.3 µmol/L, respectively. Recoveries in the 97 to 118% range were obtained using sweat samples spiked with lactate at three concentration levels, indicating an acceptable accuracy. The intraday and interday precisions were 1.49 and 7.08%, respectively. The proposed CE-C4 D method can be a starting point for monitoring lactate concentrations in sweat samples for diagnostics, physiological studies, and sports performance assessment applications.
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Ácidos Alcanossulfônicos , Ácido Láctico , Morfolinas , Suor , Humanos , Cetrimônio , Eletroforese Capilar/métodos , Condutividade ElétricaRESUMO
Therapeutic peptides are a growing class of innovative drugs with high efficiency and a low risk of adverse effects. These biomolecules fall within the molecular mass range between that of small molecules and proteins. However, their inherent instability and potential for degradation underscore the importance of reliable and effective analytical methods for pharmaceutical quality control, therapeutic drug monitoring, and compliance testing. Liquid chromatography-mass spectrometry (LC-MS) has long time been the "gold standard" conventional method for peptide analysis, but capillary electrophoresis (CE) is increasingly being recognized as a complementary and, in some cases, superior, highly efficient, green, and cost-effective alternative technique. CE can separate peptides composed of different amino acids owing to differences in their net charge and size, determining their migration behavior in an electric field. This review provides a comprehensive overview of therapeutic peptides that have been used in the clinical environment for the last 25 years. It describes the properties, classification, current trends in development, and clinical use of therapeutic peptides. From the analytical point of view, it discusses the challenges associated with the analysis of therapeutic peptides in pharmaceutical and biological matrices, as well as the evaluation of CE as a whole and the comparison with LC methods. The article also highlights the use of microchip electrophoresis, nonaqueous CE, and nonconventional hydrodynamically closed CE systems and their applications. Overall, the article emphasizes the importance of developing new CE-based analytical methods to ensure the high quality, safety, and efficacy of therapeutic peptides in clinical practice.
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Peptídeos , Proteínas , Peptídeos/análise , Proteínas/análise , Eletroforese Capilar/métodos , Aminoácidos , Preparações FarmacêuticasRESUMO
The successful development of Sacituzumab Govitecan and Trastuzumab Deruxtecan has made camptothecin derivatives one of the most popular payloads for antibody-drug conjugates (ADCs). Camptothecin and its derivatives all exist in a pH-dependent equilibrium between the carboxylate and lactone forms. Such transformation may lead to differences in the ratio of the two molecular forms in calibration standards and biological matrix (bio-matrix) samples, thereby leading to inaccurate conjugated antibody results. In this study, we reported an enzyme-linked immunosorbent assay (ELISA) free of the aforementioned influence for the detection of the Exatecans-conjugated antibody (conjugated SM001) in cynomolgus monkey serum. The assay was developed by first acidifying all samples with glacial acetic acid (HAc), then performing neutralization and thereafter capturing conjugated SM001 with anti-Exatecan monoclonal antibody (mAb) and detecting it with biotinylated Nectin4 (hNectin4-Bio) and horseradish peroxidase-labeled streptavidin (SA-HRP). Results showed that all tested performance parameters met the acceptance criteria. The conjugated SM001 concentrations obtained were in parallel to but slightly lower than total antibody (TAb) throughout the pharmacokinetic (PK) study, revealing that the assay strategy implemented for conjugated SM001 measurement worked well for the elimination of interference triggered by the heterogeneous existence of the lactone and carboxylate forms of Exatecan (lactone-Exatecan and carboxylate-Exatecan).
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Oral endocrine therapies (OET) for breast cancer treatment need to be taken over a long period of time and are associated with considerable side effects. Therefore, adherence to OET is an important issue and of high clinical significance for breast cancer patients' caregivers. We hypothesized that a new bioanalytical strategy based on liquid chromatography and high-resolution mass spectrometry might be suitable for unbiased adherence monitoring (AM) of OET. Four different biomatrices (plasma, urine, finger prick blood by volumetric absorptive microsampling (VAMS), oral fluid (OF)) were evaluated regarding their suitability for AM of the OET abemaciclib, anastrozole, exemestane, letrozole, palbociclib, ribociclib, tamoxifen, and endoxifen. An analytical method was developed and validated according to international recommendations. The analytical procedures were successfully validated in all sample matrices for most analytes, even meeting requirements for therapeutic drug monitoring. Chromatographic separation of analytes was achieved in less than 10 min and limits of quantification ranged from 1 to 1000 ng/mL. The analysis of 25 matching patient samples showed that AM of OET is possible using all four matrices with the exception of, e.g., letrozole and exemestane in OF. We were able to show that unbiased bioanalytical AM of OET was possible using different biomatrices with distinct restrictions. Sample collection of VAMS was difficult in most cases due to circulatory restraints and peripheral neuropathy in fingers and OF sampling was hampered by dry mouth syndrome in some cases. Although parent compounds could be detected in most of the urine samples, metabolites should be included when analyzing urine or OF. Plasma is currently the most suitable matrix due to available reference concentrations.
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Antineoplásicos Hormonais , Neoplasias da Mama , Monitoramento de Medicamentos , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos Hormonais/sangue , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/urina , Monitoramento de Medicamentos/métodos , Cromatografia Líquida/métodos , Administração Oral , Espectrometria de Massas/métodos , Letrozol/sangue , Adesão à Medicação , Limite de Detecção , Tamoxifeno/uso terapêutico , Tamoxifeno/sangue , Tamoxifeno/análise , Tamoxifeno/urina , Saliva/química , Androstadienos/urina , Androstadienos/análise , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Androstadienos/sangue , Anastrozol , Reprodutibilidade dos TestesRESUMO
Metal-organic frameworks (MOFs), as porous materials, have great potential for exploring high-performance electrochemiluminescence (ECL) probes. However, the constrained applicability of MOFs in the realm of ECL biosensing is primarily attributed to their inadequate water stability, which consequently impairs the overall ECL efficiency. Herein, we developed a competitive ECL biosensor based on a novel tightest structural ruthenium-based organic framework emitter combining the proximity hybridization-induced catalytic hairpin assembly (CHA) strategy and the quenching effect between the Ru-MOF and ferrocene for detecting paraquat (PQ). Through a simple hydrothermal synthesis strategy, ruthenium and 2,2'-bipyrimidine (bpm) are head-to-head self-assembled to obtain a novel tightest structural Ru-MOF. Due to the metal-ligand charge-transfer (MLCT) effect between ruthenium and the bpm ligand and the connectivity between the internal chromophore units, the Ru-MOF exhibits strong ECL emissions. Meanwhile, the coordination-driven Ru-MOF utilizes strong metal-organic coordination bonds as building blocks, which effectively solves the problem of serious leakage of chromophores caused by water solubility. The sensitive analysis of PQ is realized in the range of 1 pg/mL to 1 ng/mL with a detection limit of 0.352 pg/mL. The tightest structural Ru-MOF driven by the coordination of ruthenium and bridging ligands (2,2'-bipyrimidine, bpm) provides new horizons for exploring high-performance MOF-based ECL probes for quantitative analysis of biomarkers.
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The large volumes of samples to be analysed every day would be impossible to manage without laboratory automation. As laboratory procedures have progressed, so have the tasks of laboratory personnel. With this feature article, we would like to provide (bio)chemical practitioners with little or no knowledge of laboratory automation with a guide to help them decide whether to implement laboratory automation and find a suitable system. Especially in small- and medium-sized laboratories, operating a laboratory system means having bioanalytical knowledge, but also being familiar with the technical aspects. However, time, budget and personnel limitations allow little opportunity for personnel to get into the depths of laboratory automation. This includes not only the operation, but also the decision to purchase an automation system. Hasty investments do not only result in slow or non-existent cost recovery, but also occupy valuable laboratory space. We have structured the article as a decision tree, so readers can selectively read chapters that apply to their individual situation. This flexible approach allows each reader to create a personal reading flow tailored to their specific needs. We tried to address a variety of perspectives on the topic, including people who are either supportive or sceptical of laboratory automation, personnel who want or need to automate specific processes, those who are unsure whether to automate and those who are interested in automation but do not know which areas to prioritize. We also help to make a decision whether to reactivate or discard already existing and unused laboratory equipment.
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Antibodies for treatment and prophylaxis against SARS-CoV-2 are needed particularly for immunocompromised individuals, who cannot adequately benefit from vaccination. To address this need, Aerium Therapeutics is developing antibodies targeting the SARS-CoV-2 spike protein. A bioanalytical method to quantify fully human monoclonal antibodies in a population with widely varying anti-spike antibody titers is required to investigate the pharmacokinetics of these antibodies in clinical trials. To eliminate interference from endogenous anti-spike protein antibodies, an HPLC-MS/MS assay was developed to quantify the investigational monoclonal antibodies (AER001 and AER002) by targeting signature peptides spanning the monoclonal antibodies' CDR regions. By optimizing and comparing affinity capture and ammonium sulphate precipitation, it was demonstrated that both procedures allowed accurate and precise quantification of AER001 and AER002 in human serum with comparable sensitivity. Ammonium sulphate precipitation outperformed immunocapture due to its simplicity and speed at lower cost and a full bioanalytical method validation was performed in human serum. The assay was also validated for human nasal lining fluid extract with a 50-fold lower limit of quantification and was shown to deliver similar sensitivity to previously published affinity capture HPLC-MS/MS assays. Finally, the CDR-derived signature peptides were also generated by tryptic digestion of blank serum in some individuals, an important caveat for HPLC-MS/MS strategies targeting human monoclonal antibodies. In summary, the presented results show that ammonium sulphate precipitation and HPLC-MS/MS allow accurate and precise quantification of monoclonals in clinical studies. The developed methods demonstrate that HPLC-MS/MS can reliably quantify human monoclonal antibodies even when endogenous antibodies with overlapping specificities are present and are crucial for the clinical testing of two investigational COVID-19 monoclonals.
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Anticorpos Monoclonais , Anticorpos Antivirais , COVID-19 , Humanos , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Cromatografia Líquida de Alta Pressão/métodos , COVID-19/sangue , Limite de Detecção , Espectrometria de Massa com Cromatografia Líquida , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Espectrometria de Massas em Tandem/métodosRESUMO
Liquid chromatography-mass spectrometry (LC-MS) has emerged as a powerful analytical technique for analyzing complex biological samples. Among various chromatographic stationary phases, porous graphitic carbon (PGC) columns have attracted significant attention due to their unique properties-such as the ability to separate both polar and non-polar compounds and their stability through all pH ranges and to high temperatures-besides the compatibility with LC-MS. This review discusses the applicability of PGC for SPE and separation in LC-MS-based analyses of human biological samples, highlighting the diverse applications of PGC-LC-MS in analyzing endogenous metabolites, pharmaceuticals, and biomarkers, such as glycans, proteins, oligosaccharides, sugar phosphates, and nucleotides. Additionally, the fundamental principles underlying PGC column chemistry and its advantages, challenges, and advances in method development are explored. This comprehensive review aims to provide researchers and practitioners with a valuable resource for understanding the capabilities and limitations of PGC columns in LC-MS-based analysis of human biological samples, thereby facilitating advancements in analytical methodologies and biomedical research.
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Given the inherent complexities of bioanalysis, the role of incurred sample reanalysis (ISR) is increasingly appreciated in regulatory bioanalysis. Incurred sample reanalysis has evolved as an integral part of an assay to ensure method reproducibility. The current regulatory ISR guidelines do not provide clarity regarding ISR assessment for chiral drugs comprising enantiomers. Because chiral assays evaluate two enantiomers, there are additional complexities associated with the ISR data generation and interpretation. Based on the current literature, the practices for conducting ISR in chiral methods were reviewed and assessed. While ISR was conducted in chiral methods for both enantiomers using the acceptance criteria prescribed for non-chiral methods, there may be a need to streamline the nuances of ISR data interpretation and define the ISR requirements for chiral methods. The article provides perspectives on the ISR of enantiomeric drugs, including strategy development, by providing various hypothetical scenarios and possible considerations for defining ISR evaluation for chiral assays.
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Estereoisomerismo , Preparações Farmacêuticas/química , Preparações Farmacêuticas/sangue , Preparações Farmacêuticas/análise , Reprodutibilidade dos Testes , HumanosRESUMO
Conventional spherical nucleic acid enzymes (SNAzymes), made with gold nanoparticle (AuNPs) cores and DNA shells, are widely applied in bioanalysis owing to their excellent physicochemical properties. Albeit important, the crowded catalytic units (such as G-quadruplex, G4) on the limited AuNPs surface inevitably influence their catalytic activities. Herin, a hybridization chain reaction (HCR) is employed as a means to expand the quantity and spaces of G4 enzymes for their catalytic ability enhancement. Through systematic investigations, we found that when an incomplete G4 sequence was linked at the sticky ends of the hairpins with split modes (3:1 and 2:2), this would significantly decrease the HCR hybridization capability due to increased steric hindrance. In contrast, the HCR hybridization capability was remarkably enhanced after the complete G4 sequence was directly modified at the non-sticky end of the hairpins, ascribed to the steric hindrance avoided. Accordingly, the improved SNAzymes using HCR were applied for the determination of AFB1 in food samples as a proof-of-concept, which exhibited outstanding performance (detection limit, 0.08 ng/mL). Importantly, our strategy provided a new insight for the catalytic activity improvement in SNAzymes using G4 as a signaling molecule.
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Nanopartículas Metálicas , Ácidos Nucleicos , Aflatoxina B1 , Ouro , Hibridização de Ácido NucleicoRESUMO
BACKGROUND: The development of an anti-drug antibody (ADA)-tolerant pharmacokinetic (PK) assay is important when the drug exposure is irrelevant to toxicity in the presence of ADA. We aimed to develop and validate an ADA-tolerant assay for an exatecan-based antibody-drug conjugate (ADC) in monkey plasma. RESULTS: The assay tolerated 5.00 µg/mL of ADA at 12 µg/mL of ADC. Its accuracy and precision results satisfied the acceptance criteria. Furthermore, the assay was free from hook and matrix effects and exhibited good dilutional linearity. Additionally, the ADC in plasma samples was stable under different storage conditions. METHOD: An ADA-tolerant ADC assay was configured with an anti-payload antibody for capture, and a drug-target protein combined with a horseradish peroxidase (HRP)-labeled antibody against a drug-target-protein tag for detection. Samples were firstly acidified to dissociate drug and ADA complexes, and to convert the carboxylate form to the lactone form of exatecan molecules; then, the ADAs in the samples were removed with a naked antibody-coated microplate. The treated samples were further incubated with coated anti-payload antibody and captured ADC molecules were quantified by the detection reagent. The developed assay was optimized and validated against regulatory guidelines. CONCLUSIONS: The assay met both methodological and sample-related ADA tolerance requirements, and was applicable to a nonclinical study in cynomolgus monkeys.
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Camptotecina/análogos & derivados , Imunoconjugados , Animais , Haplorrinos , AnticorposRESUMO
The selective quantification of copper ions (Cu2+ ) in biosamples holds great importance for disease diagnosis, treatment, and prognosis since the Cu2+ level is closely associated with the physiological state of the human body. While it remains a long-term challenge due to the extremely low level of free Cu2+ and the potential interference by the complex matrices. Here, a pore-engineered hydrogen-bonded organic framework (HOF) fluorosensor is constructed enabling the ultrasensitive and highly selective detection of free Cu2+ . Attributing to atomically precise functionalization of active amino "arm" within the HOF pores and the periodic π-conjugated skeleton, this porous HOF fluorosensor affords high affinity toward Cu2+ through double copper-nitrogen (CuâN) coordination interactions, resulting in specific fluorescence quenching of the HOF as compared with a series of substances ranging from other metal ions, metabolites, amino acids to proteins. Such superior fluorescence quenching effect endows the Cu2+ quantification by this new HOF sensor with a wide linearity of 50-20 000 nm, a low detection limit of 10 nm, and good recoveries (89.5%-115%) in human serum matrices, outperforming most of the reported approaches. This work highlights the practicability of hydrogen-bonded supramolecular engineering for designing facile and ultrasensitive biosensors for clinical free Cu2+ determination.
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Analysis of cellular composition and metabolism at a single-cell resolution allows gaining more information about complex relationships of cells within tissues or whole living organisms by resolving the variance stemming from the cellular heterogeneity. Mass spectrometry (MS) is a perfect analytical tool satisfying the demanding requirements of detecting and identifying compounds present in such ultralow-volume samples of high chemical complexity. However, the method of sampling and sample ionization is crucial in obtaining relevant information. In this work, we present a microfluidic sampling platform that integrates single-cell extraction from MS-incompatible media with electrical cell lysis and nanoESI-MS analysis of human erythrocytes. Hemoglobin alpha and beta chains (300 amol/cell) were successfully identified in mass spectra of single-erythrocyte lysates.
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Microfluídica , Espectrometria de Massas por Ionização por Electrospray , Humanos , Espectrometria de Massas por Ionização por Electrospray/métodos , Microfluídica/métodos , Eritrócitos , Dispositivos Lab-On-A-ChipRESUMO
Most antiretrovirals (ARVs) have intracellular therapeutic target sites and therefore, their plasma concentration may be misleading when relating to their efficacy or toxicity. A bioanalytical method for quantification of the ARV drug bictegravir (BTG) in its target site peripheral blood mononuclear cells (PBMCs) is not available till date. This is the first time to establish a sufficiently sensitive mass spectrometry-based bioanalytical method to quantify BTG in both rat PBMCs and plasma. The developed method was validated over the range of 1 ng/ml to 100 ng/ml and 0.005 ng-10ng/sample for plasma and PBMCs, respectively. For PBMCs, average accuracy and precision at four quality control levels were found to be 93.30%-110.00% and 6.52%-8.25%, respectively. Plasma and intracellular pharmacokinetics of BTG was evaluated by the developed method in rats and a lack of accumulation of BTG in the PBMCs was observed. Pearson correlation coefficient data analysis indicated a moderated correlation between plasma and PBMC concentration of BTG. Therefore, it will be beneficial to include a quantification plan for BTG in its actual therapeutic target site during all its future research and development work. This reported method can be useful for site-specific monitoring of BTG in research laboratories and pharmaceutical industries.
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Leucócitos Mononucleares , Espectrometria de Massas em Tandem , Animais , Ratos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Amidas , Reprodutibilidade dos TestesRESUMO
The deployment of metal-organic frameworks (MOFs) in a plethora of analytical and bioanalytical applications is a growing research area. Their unique properties such as high but tunable porosity, well-defined channels or pores, and ease of post-synthetic modification to incorporate additional functional units make them ideal candidates for sensing applications. This is possible because the interaction of analytes with a MOF often results in a change in its structure, eventually leading to a modification of the intrinsic physicochemical properties of the MOF which is then transduced into a measurable signal. The high porosity allows for the adsorption of analytes very efficiently, while the tunable pore sizes/nature and/or installation of specific recognition groups allow modulating the affinity towards different classes of compounds, which in turn lead to good sensor sensitivity and selectivity, respectively. Some figures are given to illustrate the potential of MOF-based sensors in the most relevant application fields, and future challenges and opportunities to their possible translation from academia (i.e., laboratory testing of MOF sensing properties) to industry (i.e., real-world analytical sensor devices) are critically discussed.