Rapid progress in identifying biomarkers that are hallmarks of disease has increased demand for high-performance detection technologies. Implementation of electrochemical methods in clinical analysis ...may provide an effective answer to the growing need for rapid, specific, inexpensive, and fully automated means of biomarker analysis. This Review summarizes advances from the past 5 years in the development of electrochemical sensors for clinically relevant biomolecules, including small molecules, nucleic acids, and proteins. Various sensing strategies are assessed according to their potential for reaching relevant limits of sensitivity, specificity, and degrees of multiplexing. Furthermore, we address the remaining challenges and opportunities to integrate electrochemical sensing platforms into point-of-care solutions.
Circulating tumour nucleic acids (ctNAs) are released from tumours cells and can be detected in blood samples, providing a way to track tumors without requiring a tissue sample. This “liquid biopsy” ...approach has the potential to replace invasive, painful, and costly tissue biopsies in cancer diagnosis and management. However, a very sensitive and specific approach is required to detect relatively low amounts of mutant sequences linked to cancer because they are masked by the high levels of wild‐type sequences. This review discusses high‐performance nucleic acid biosensors for ctNA analysis in patient samples. We compare sequencing‐ and amplification‐based methods to next‐generation sensors for ctDNA and ctRNA (including microRNA) profiling, such as electrochemical methods, surface plasmon resonance, Raman spectroscopy, and microfluidics and dielectrophoresis‐based assays. We present an overview of the analytical sensitivity and accuracy of these methods as well as the biological and technical challenges they present.
Biopsies from blood samples: In this minireview, the development of sensors for non‐invasive cancer diagnosis and management, an approach referred to as “liquid biopsy”, is discussed. This application has very demanding performance requirements as high sensitivity and specificity are needed to detect bloodborne nucleic acids in patient samples. Electrochemical and spectroscopic approaches that demonstrate potential for this important biomedical problem are discussed.
Diagnosing disease at the molecular level rapidly and with a high level of sensitivity and specificity is a critical capability for modern medicine. Rapid detection of small numbers of biomarkers of ...early disease in complex, heterogeneous clinical specimens represents a Holy Grail that will have a significant impact on human health.
Reduced-dimensional metal halide perovskites (RDPs) have attracted significant attention in recent years due to their promising light harvesting and emissive properties. We sought to increase the ...systematic understanding of how RDPs are formed. Here we report that layered intermediate complexes formed with the solvent provide a scaffold that facilitates the nucleation and growth of RDPs during annealing, as observed via in situ X-ray scattering. Transient absorption spectroscopy of RDP single crystals and films enables the identification of the distribution of quantum well thicknesses. These insights allow us to develop a kinetic model of RDP formation that accounts for the experimentally observed size distribution of wells. RDPs exhibit a thickness distribution (with sizes that extend above n = 5) determined largely by the stoichiometric proportion between the intercalating cation and solvent complexes. The results indicate a means to control the distribution, composition and orientation of RDPs via the selection of the intercalating cation, the solvent and the deposition technique.
The existence of cellular heterogeneity and its central relevance to biological phenomena provides a strong rationale for a need for analytical methods that enable analysis at the single-cell level. ...Analysis of the genome and transcriptome is possible at the single-cell level, but the comprehensive interrogation of the proteome with this level of resolution remains challenging. Single-cell protein analysis tools are advancing rapidly, however, and providing insights into collections of proteins with great relevance to cell and disease biology. Here, we review single-cell protein analysis technologies and assess their advantages and limitations. The emerging technologies presented have the potential to reveal new insights into tumour heterogeneity and therapeutic resistance, elucidate mechanisms of immune response and immunotherapy, and accelerate drug discovery.
Low-dimensional perovskites have-in view of their high radiative recombination rates-shown great promise in achieving high luminescence brightness and colour saturation. Here we investigate the ...effect of electron-phonon interactions on the luminescence of single crystals of two-dimensional perovskites, showing that reducing these interactions can lead to bright blue emission in two-dimensional perovskites. Resonance Raman spectra and deformation potential analysis show that strong electron-phonon interactions result in fast non-radiative decay, and that this lowers the photoluminescence quantum yield (PLQY). Neutron scattering, solid-state NMR measurements of spin-lattice relaxation, density functional theory simulations and experimental atomic displacement measurements reveal that molecular motion is slowest, and rigidity greatest, in the brightest emitter. By varying the molecular configuration of the ligands, we show that a PLQY up to 79% and linewidth of 20 nm can be reached by controlling crystal rigidity and electron-phonon interactions. Designing crystal structures with electron-phonon interactions in mind offers a previously underexplored avenue to improve optoelectronic materials' performance.
The measurement of physicochemical parameters in living cells can provide information on individual cellular organelles, helping us to understand subcellular function in health and disease. While ...organelle‐specific chemical probes have allowed qualitative evaluation of microenvironmental variations, the simultaneous quantification of mitochondrial local microviscosity (ηm) and micropolarity (ϵm), along with concurrent structural variations, has remained an unmet need. Herein, we describe a new multifunctional mitochondrial probe (MMP) for simultaneous monitoring of ηm and ϵm by fluorescence lifetime and emission intensity recordings, respectively. The MMP enables highly precise measurements of ηm and ϵm in the presence of a variety of agents perturbing cellular function, and the observed changes can also be correlated with alterations in mitochondrial network morphology and motility. This strategy represents a promising tool for the analysis of subtle changes in organellar structure.
A fluorescent probe enables highly precise, quantitative measurements of local mitochondrial microviscosity and micropolarity in the presence of a variety of agents perturbing cellular function. The observed changes could also be correlated with alterations in mitochondrial network morphology and motility.
Analysis of circulating tumor cells (CTCs) collected from patient's blood offers a broad range of opportunities in the field of precision oncology. With new advances in profiling technology, it is ...now possible to demonstrate an association between the molecular profiles of CTCs and tumor response to therapy. In this Review, we discuss mechanisms of tumor resistance to therapy and their link to phenotypic and genotypic properties of CTCs. We summarize key technologies used to isolate and analyze CTCs and discuss recent clinical studies that examined CTCs for genomic and proteomic predictors of responsiveness to therapy. We also point out current limitations that still hamper the implementation of CTCs into clinical practice. We finally reflect on how these shortcomings can be addressed with the likely contribution of multiparametric approaches and advanced data analytics.
This Review highlights the emerging role of circulating tumor cell (CTC) profiling in precision oncology. We summarize key technologies currently employed for CTC isolation and analysis and discuss recent clinical studies that examined CTCs for genomic and proteomic predictors of therapeutic response. We point out challenges associated with implementation of CTC profiling into clinical practice and reflect on potential solutions.
Mitochondria, colloquially known as “the powerhouse of the cell”, play important roles in production, but also in processes critical for cellular fate such as cell death, differentiation, signaling, ...metabolic homeostasis, and innate immunity. Due to its many functions in the cell, the mitochondria have been linked to a variety of human illnesses such as diabetes, cancer, and neurodegenerative diseases. In order to further our understanding and pharmaceutical targeting of this critical organelle, effective strategies must be employed to breach the complex barriers and microenvironment of mitochondria. Here, we summarize advancements in mitochondria-targeted probes and therapeutics.
Thermally-induced tensile strain that remains in perovskite films following annealing results in increased ion migration and is a known factor in the instability of these materials. ...Previously-reported strain regulation methods for perovskite solar cells (PSCs) have utilized substrates with high thermal expansion coefficients that limits the processing temperature of perovskites and compromises power conversion efficiency. Here we compensate residual tensile strain by introducing an external compressive strain from the hole-transport layer. By using a hole-transport layer with high thermal expansion coefficient, we compensate the tensile strain in PSCs by elevating the processing temperature of hole-transport layer. We find that compressive strain increases the activation energy for ion migration, improving the stability of perovskite films. We achieve an efficiency of 16.4% for compressively-strained PSCs; and these retain 96% of their initial efficiencies after heating at 85 °C for 1000 hours-the most stable wide-bandgap perovskites (above 1.75 eV) reported so far.
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