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.
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.
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.
Progress toward the development of minimally invasive liquid biopsies of disease is being bolstered by breakthroughs in the analysis of circulating tumor DNA (ctDNA): DNA released from cancer cells ...into the bloodstream. However, robust, sensitive, and specific methods of detecting this emerging analyte are lacking. ctDNA analysis has unique challenges, since it is imperative to distinguish circulating DNA from normal cells vs mutation-bearing sequences originating from tumors. Here we report the electrochemical detection of mutated ctDNA in samples collected from cancer patients. By developing a strategy relying on the use of DNA clutch probes (DCPs) that render specific sequences of ctDNA accessible, we were able to readout the presence of mutated ctDNA. DCPs prevent reassociation of denatured DNA strands: they make one of the two strands of a dsDNA accessible for hybridization to a probe, and they also deactivate other closely related sequences in solution. DCPs ensure thereby that only mutated sequences associate with chip-based sensors detecting hybridization events. The assay exhibits excellent sensitivity and specificity in the detection of mutated ctDNA: it detects 1 fg/μL of a target mutation in the presence of 100 pg/μL of wild-type DNA, corresponding to detecting mutations at a level of 0.01% relative to wild type. This approach allows accurate analysis of samples collected from lung cancer and melanoma patients. This work represents the first detection of ctDNA without enzymatic amplification.
Mitochondria are energy-producing organelles with essential functions in cell biology, and mitochondrial dysfunction is linked to a wide range of human diseases. Efforts to better understand ...mitochondrial biology have been limited by the lack of tools for manipulating and detecting processes occurring within the organelle. Here, we highlight recent significant advances in mitochondrial chemical biology that have produced new tools and techniques for studying mitochondria. Specifically, we focus on the development of chemical tools to perturb mitochondrial biochemistry, probes allowing precise measurement of mitochondrial function, and new techniques for high-throughput characterization of the mitochondrial proteome. Taken together, these advances in chemical biology will enable exciting new directions in mitochondrial research.
Mitochondria are complex organelles in the crux of many critical cellular processes, yet their biology remains incompletely understood. Wisnovsky et al. review how chemical biology is enabling studies of mitochondria and taking mitochondrial research in new directions.
Though the history of self‐healing materials stretches far back to the mid‐20th century, it is only in recent years where such unique classes of materials have begun to find use in ...bioelectronics—itself a burgeoning area of research. Inspired by the natural ability of biological tissue to self‐repair, self‐healing materials play a multifaceted role in the context of soft, wireless bioelectronic systems, in that they can not only serve as a protective outer shell or substrate for the internal electronic circuitry—analogous to the mechanical barrier that skin provides for the human body—but also, and most importantly, act as an active sensing safeguard against mechanical damage to preserve device functionality and enhance overall durability. This perspective presents the historical overview, general design principles, recent developments, and future outlook of self‐healing materials for bioelectronic devices, which integrates topics in many research disciplines—from materials science and chemistry to electronics and bioengineering—together.
The convergence of self‐healing materials and bioelectronics is yielding novel technologies that possess properties analogous to biological tissue, preserving device operation and functionality in the case of damage. In this perspective, outline the historical overview, general design principles, recent developments, and future outlook of self‐healing materials for bioelectronic devices—an exciting research direction for changing the health monitoring paradigm.
The selective permeability of the plasma membrane prohibits most exogenous agents from gaining cellular access. Since many therapeutics and reporter molecules must be internalized for activity, ...crossing the plasma membrane is essential. A very effective class of transporters harnessed for this purpose are cell penetrating peptides (CPPs), a group of short cationic sequences with a remarkable capacity for membrane translocation. Since their discovery in 1988, CPPs have been employed for the delivery of a wide variety of cargo including small molecules, nucleic acids, antibodies and nanoparticles. This review describes recent advances in the use of CPPs for biological and therapeutic applications. In particular, an emphasis is placed on novel systems and insights acquired since 2006. Basic research on CPPs has recently yielded techniques that provide further information on the controversial mechanism of CPP uptake and has also resulted in the development of new model membrane systems to evaluate these mechanisms. In addition, recent use of CPPs for the development of new cellular imaging tools, biosensors, or biomolecular delivery systems have been highlighted. Lastly, novel peptide delivery vectors, designed to tackle some of the drawbacks of CPPs and enhance their versatility, will be described. This review will illustrate the diverse applications for which CPPs have been harnessed and also demonstrate the remarkable advancements these peptides have facilitated in cell biology.
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