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.
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.
Detection and identification of special cells via aptamer-based nano-conjugates sensors have been revolutionized over the past few years. These sensing platforms rely on selecting aptamers using ...systematic evolution of ligands by exponential enrichment (SELEX) in vitro, which allows for sensitive detection of cells. Integration of the aptamer-based sensors (aptasensors) with nanomaterials offers enhanced specificity and sensitivity, which in turn, offers great promise for numerous applications, spanning from bioanalysis to biomedical applications. Accordingly, the demand for using aptamer-conjugated nanomaterials for various applications has progressively increased over the past years. In light of this, this Review seeks to highlight the recent advances in the development of aptamer-conjugated nanomaterials and their utilization for the detection of various pathogens involved in infectious diseases and food contamination.
•Detection of pathogens using biosensors is critical for translation into the clinic.•Aptamers offer a variety of merits to sensing platforms compared to conventional recognition elements.•A variety of nanomaterials have been utilized to design the sensing interfaces.•Nanostructured sensors leverage the analytical performance of aptasensors.
Cell morphology and geometry affect cellular processes such as stem cell differentiation, suggesting that these parameters serve as fundamental regulators of biological processes within the cell. ...Hierarchical architectures featuring micro- and nanotopographical features therefore offer programmable systems for stem cell differentiation. However, a limited number of studies have explored the effects of hierarchical architectures due to the complexity of fabricating systems with rationally tunable micro- and nanostructuring. Here, we report three-dimensional (3D) nanostructured microarchitectures that efficiently regulate the fate of human mesenchymal stem cells (hMSCs). These nanostructured architectures strongly promote cell alignment and efficient neurogenic differentiation where over 85% of hMSCs express microtubule-associated protein 2 (MAP2), a mature neural marker, after 7 days of culture on the nanostructured surface. Remarkably, we found that the surface morphology of nanostructured surface is a key factor that promotes neurogenesis and that highly spiky structures promote more efficient neuronal differentiation. Immunostaining and gene expression profiling revealed significant upregulation of neuronal markers compared to unpatterned surfaces. These findings suggest that the 3D nanostructured microarchitectures can play a critical role in defining stem cell behavior.
Over the last decade, significant progress has been made towards the development of approaches that enable the capture of rare circulating tumor cells (CTCs) from the blood of cancer patients, a ...critical capability for noninvasive tumor profiling. These advances have leveraged new insights in materials chemistry and microfluidics and allowed the capture and enumeration of CTCs with unprecedented sensitivity. However, it has become increasingly clear that simply capturing and counting tumor cells launched into the bloodstream may not provide the information needed to advance our understanding of the biology of these rare cells, or to allow us to better exploit them in medicine. A variety of advances have now emerged demonstrating that more information can be extracted from CTCs with next‐generation devices and materials featuring tailored physical and chemical properties. In this Minireview, the last ten years of work in this area will be discussed, with an emphasis on the groundbreaking work of the last five years, during which the focus has moved beyond the simple capture of CTCs and gravitated towards approaches that enable in‐depth analysis.
Deadliest catch: Over the last decade, significant progress has been made towards the capture of rare circulating tumor cells (CTCs) from the blood of cancer patients, a critical capability for noninvasive tumor profiling. This Minireview summarizes recent breakthroughs and focuses on how new devices and materials have allowed this rapidly advancing field to move beyond enumeration and towards comprehensive characterization of CTCs.
In living systems, interfacial molecular interactions control many biological processes. New stimuli‐responsive strategies are desired to provide versatile model systems that can regulate cell ...behavior in vitro. Described here are potential‐responsive surfaces that control cell adhesion and release as well as stem cell differentiation. Cell adhesion can be modulated dynamically by applying negative and positive potentials to surfaces functionalized with tailored monolayers. This process alters cell morphology and ultimately controls behavior and the fate of the cells. Cells can be detached from the electrode surface as intact clusters with different geometries using electrochemical potentials. Importantly, morphological changes during adhesion guide stem cell differentiation. The higher accessibility of the peptide under a positive applied potential causes phenotypic changes in the cells that are hallmarks of osteogenesis, whereas lower accessibility of the peptide promoted by negative potentials leads to adipogenesis.
On the surface: Potential‐responsive surfaces are used to control cell adhesion and release, as well as stem cell differentiation. The cell adhesion can be modulated dynamically by applying a negative and positive potential to surfaces functionalized with specific molecular structures. This process alters cell morphology and ultimately defines the behavior and fate of the cells.
During cancer progression, tumors shed circulating tumor cells (CTCs) into the bloodstream. CTCs that originate from the same primary tumor can have heterogeneous phenotypes and, while some CTCs ...possess benign properties, others have high metastatic potential. Deconstructing the heterogeneity of CTCs is challenging and new methods are needed that can sort small numbers of cancer cells according to their phenotypic properties. Here we describe a new microfluidic approach that profiles, along two independent phenotypic axes, the behavior of heterogeneous cell subpopulations. Cancer cells are first profiled according to expression of a surface marker using a nanoparticle‐enabled approach. Along the second dimension, these subsets are further separated into subpopulations corresponding to migration profiles generated in response to a chemotactic agent. We deploy this new technique and find a strong correlation between the surface expression and migration potential of CTCs present in blood from mice with xenografted tumors. This system provides an important new means to characterize functional diversity in circulating tumor cells.
Chemotaxis is one principle behind a microfluidic device for the two‐dimensional phenotypic profiling of circulating tumor cells (CTCs, see figure). The device can be used to isolate phenotypically distinct cell subpopulations defined using two phenotypes—a biochemical phenotype reporting on epithelial‐to‐mesenchymal transition status, and a functional phenotype reporting on migratory potential.
There are currently no standard methods for the detection of Cryptosporidium spp., or other protozoan parasites, in foods, and existing methods are often inadequate, with low and variable recovery ...efficiencies. Food testing is difficult due to the low concentrations of parasites, the difficulty in eluting parasites from some foods, the lack of enrichment methods, and the presence of PCR inhibitors. The main objectives of the present study were to obtain DNA aptamers binding to the oocyst wall of C. parvum, and to use the aptamers to detect the presence of this parasite in foods. DNA aptamers were selected against C. parvum oocysts using SELEX (Systematic Evolution of Ligands by EXponential enrichment). Ten rounds of selection led to the discovery of 14 aptamer clones with high affinities for C. parvum oocysts. For detecting parasite-bound aptamers, a simple electrochemical sensor was employed, which used a gold nanoparticle-modified screen-printed carbon electrode. This aptasensor was fabricated by self-assembling a hybrid of a thiolated ssDNA primer and the anti- C. parvum aptamer. Square wave voltammetry was employed to quantitate C. parvum in the range of 150 to 800 oocysts, with a detection limit of approximately 100 oocysts. The high sensitivity and specificity of the developed aptasensor suggests that this novel method is very promising for the detection and identification of C. parvum oocysts on spiked fresh fruits, as compared to conventional methods such as microscopy and PCR.
DNA aptamers were developed against murine norovirus (MNV) using SELEX (Systematic Evolution of Ligands by EXponential enrichment). Nine rounds of SELEX led to the discovery of AG3, a promising ...aptamer with very high affinity for MNV as well as for lab-synthesized capsids of a common human norovirus (HuNoV) outbreak strain (GII.3). Using fluorescence anisotropy, AG3 was found to bind with MNV with affinity in the low picomolar range. The aptamer could cross-react with HuNoV though it was selected against MNV. As compared to a non-specific DNA control sequence, the norovirus-binding affinity of AG3 was about a million-fold higher. In further tests, the aptamer also showed nearly a million-fold higher affinity for the noroviruses than for the feline calicivirus (FCV), a virus similar in size and structure to noroviruses. AG3 was incorporated into a simple electrochemical sensor using a gold nanoparticle-modified screen-printed carbon electrode (GNPs-SPCE). The aptasensor could detect MNV with a limit of detection of approximately 180 virus particles, for possible on-site applications. The lead aptamer candidate and the aptasensor platform show promise for the rapid detection and identification of noroviruses in environmental and clinical samples.
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