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A systematic investigation of stem cell-derived neural interfaces can facilitate the discovery of the molecular mechanisms behind cell behavior in neurological disorders and accelerate the development of stem cell-based therapies. Nevertheless, high-throughput investigation of the cell-type-specific biophysical cues associated with stem cell-derived neural interfaces continues to be a significant obstacle to overcome. To this end, we developed a combinatorial nanoarray-based method for high-throughput investigation of neural interface micro-/nanostructures (physical cues comprising geometrical, topographical, and mechanical aspects) and the effects of these complex physical cues on stem cell fate decisions. Furthermore, by applying a machine learning (ML)-based analytical approach to a large number of stem cell-derived neural interfaces, we comprehensively mapped stem cell adhesion, differentiation, and proliferation, which allowed for the cell-type-specific design of biomaterials for neural interfacing, including both adult and human-induced pluripotent stem cells (hiPSCs) with varying genetic backgrounds. In short, we successfully demonstrated how an innovative combinatorial nanoarray and ML-based platform technology can aid with the rational design of stem cell-derived neural interfaces, potentially facilitating precision, and personalized tissue engineering applications. 

Abstract Immunotherapy has reached clinical success in the last decade, with the emergence of new and effective treatments such as checkpoint blockade therapy and CAR T-cell therapy that have drastically improved patient outcomes. Still, these therapies can be improved to limit off-target effects, mitigate systemic toxicities, and increase overall efficacies. Nanoscale engineering offers strategies that enable researchers to attain these goals through the manipulation of immune cell functions, such as enhancing immunity against cancers and pathogens, controlling the site of immune response, and promoting tolerance via the delivery of small molecule drugs or biologics. By tuning the properties of the nanomaterials, such as size, shape, charge, and surface chemistry, different types of immune cells can be targeted and engineered, such as dendritic cells for immunization, or T cells for promoting adaptive immunity. Researchers have come to better understand the critical role the immune system plays in the progression of pathologies besides cancer, and developing nanoengineering approaches that seek to harness the potential of immune cell activities can lead to favorable outcomes for the treatment of injuries and diseases. 

Protein adsorption to solid carbohydrate interfaces is critical to many biological processes, particularly in biomass deconstruction. To engineer more-efficient enzymes for biomass deconstruction into sugars, it is necessary to characterize the complex protein–carbohydrate interfacial interactions. A carbohydrate-binding module (CBM) is often associated with microbial surface-tethered cellulosomes or secreted cellulase enzymes to enhance substrate accessibility. However, it is not well known how CBMs recognize, bind, and dissociate from polysaccharides to facilitate efficient cellulolytic activity, due to the lack of mechanistic understanding and a suitable toolkit to study CBM–substrate interactions. Our work outlines a general approach to study the unbinding behavior of CBMs from polysaccharide surfaces using a highly multiplexed single-molecule force spectroscopy assay. Here, we apply acoustic force spectroscopy (AFS) to probe a Clostridium thermocellum cellulosomal scaffoldin protein (CBM3a) and measure its dissociation from nanocellulose surfaces at physiologically relevant, low force loading rates. An automated microfluidic setup and method for uniform deposition of insoluble polysaccharides on the AFS chip surfaces are demonstrated. The rupture forces of wild-type CBM3a, and its Y67A mutant, unbinding from nanocellulose surfaces suggests distinct multimodal CBM binding conformations, with structural mechanisms further explored using molecular dynamics simulations. Applying classical dynamic force spectroscopy theory, the single-molecule unbinding rate at zero force is extrapolated and found to agree with bulk equilibrium unbinding rates estimated independently using quartz crystal microbalance with dissipation monitoring. However, our results also highlight critical limitations of applying classical theory to explain the highly multivalent binding interactions for cellulose–CBM bond rupture forces exceeding 15 pN. 

The detection of nucleic acids and their mutation derivatives is vital for biomedical science and applications. Although many nucleic acid biosensors have been developed, they often require pretreatment processes, such as target amplification and tagging probes to nucleic acids. Moreover, current biosensors typically cannot detect sequence-specific mutations in the targeted nucleic acids. To address the above problems, herein, we developed an electrochemical nanobiosensing system using a phenomenon comprising metal ion intercalation into the targeted mismatched double-stranded nucleic acids and a homogeneous Au nanoporous electrode array (Au NPEA) to obtain (i) sensitive detection of viral RNA without conventional tagging and amplifying processes, (ii) determination of viral mutation occurrence in a simple detection manner, and (iii) multiplexed detection of several RNA targets simultaneously. As a proof-of-concept demonstration, a SARS-CoV-2 viral RNA and its mutation derivative were used in this study. Our developed nanobiosensor exhibited highly sensitive detection of SARS-CoV-2 RNA (∼1 fM detection limit) without tagging and amplifying steps. In addition, a single point mutation of SARS-CoV-2 RNA was detected in a one-step analysis. Furthermore, multiplexed detection of several SARS-CoV-2 RNAs was successfully demonstrated using a single chip with four combinatorial NPEAs generated by a 3D printing technique. Collectively, our developed nanobiosensor provides a promising platform technology capable of detecting various nucleic acids and their mutation derivatives in highly sensitive, simple, and time-effective manners for point-of-care biosensing. 

Abstract The human neurovascular system is a complex network of blood vessels and brain cells that is essential to the proper functioning of the brain. Researchers have become increasingly interested in the system for developing drugs to treat neuroinflammation. Currently, creating neurovascular models begins with animal models, followed by testing on humans in clinical trials. However, the high number of medication failures that pass through animal testing indicates that animal models do not always reflect the outcome of human clinical trials. To overcome the challenges of the issues with animal models, a neurovascular‐unit‐on‐a‐chip system is developed to accurately replicate the in vivo human neurovascular microenvironment. By replicating the human neurovascular unit, a more accurate representation of human physiology can be achieved compared to animal models. The ability to detect proinflammatory cytokines in situ and monitor physiological changes can provide an invaluable tool for evaluating the efficacy and safety of drugs. Using nanosized graphene oxide for in situ detection of inflammatory responses is an innovative approach that can advance the field of neuroinflammation research. Overall, the developed neuroinflammation‐on‐a‐chip system has the potential to provide a more efficient and effective method for developing drugs for treating neurodegenerative diseases and other central nervous system diseases. 

Stem cells show excellent potential in the field of tissue engineering and regenerative medicine based on their excellent capability to not only self-renew but also differentiate into a specialized cell type of interest. However, the lack of a non-destructive monitoring system makes it challenging to identify and characterize differentiated cells before their transplantation without compromising cell viability. Thus, the development of a non-destructive monitoring method for analyzing cell function is highly desired and can significantly benefit stem cell-based therapies. Recently, nanomaterial-based scaffolds ( e.g. , nanoarrays) have made possible considerable advances in controlling the differentiation of stem cells and characterization of the differentiation status sensitively in real time. This review provides a selective overview of the recent progress in the synthesis methods of nanoarrays and their applications in controlling stem cell fate and monitoring live cell functions electrochemically. We believe that the topics discussed in this review can provide brief and concise guidelines for the development of novel nanoarrays and promote the interest in live cell study applications. A method which can not only control but also monitor stem cell fate and function will be a promising technology that can accelerate stem cell therapies.