Modularized Field-Effect Transistor Biosensors.

Field-effect transistors (FETs), when functionalized with proper biorecognition elements (such as antibodies or enzymes), represent a unique platform for real-time, specific, label-free transduction of biochemical signals. However, direct immobilization of biorecognition molecules on FETs imposes limitations on reprogrammability, sensor regeneration, and robust device handling. Here we demonstrate a modularized design of FET biosensors with separate biorecognition and transducer modules, which are capable of reversible assembly and disassembly. In particular, hydrogel "stamps" immobilizing bioreceptors have been chosen to build biorecognition modules to reliably interface with FET transducers structurally and functionally. Successful detection of penicillin down to 0.25 mM has been achieved with a penicillinase-encoded hydrogel module, demonstrating effective signal transduction across the hybrid interface. Moreover, sequential integration of urease- and penicillinase-encoded modules on the same FET device allows us to reprogram the sensing modality without cross-contamination. In addition to independent bioreceptor encoding, the modular design also fosters sophisticated control of sensing kinetics by modulating the physiochemical microenvironment in the biorecognition modules. Specifically, the distinction in hydrogel porosity between polyethylene glycol and gelatin enables controlled access and detection of larger molecules, such as poly-l-lysine (MW 150-300 kDa), only through the gelatin module. Biorecognition modules with standardized interface designs have also been exploited to comply with additive mass fabrication by 3D printing, demonstrating potential for low cost, ease of storage, multiplexing, and great customizability for personalized biosensor production. This generic concept presents a unique integration strategy for modularized bioelectronics and could broadly impact hybrid device development.

Hydrogel Gate Graphene Field-Effect Transistors as Multiplexed Biosensors.

Nanoscale field-effect transistors (FETs) represent a unique platform for real time, label-free transduction of biochemical signals with unprecedented sensitivity and spatiotemporal resolution, yet their translation toward practical biomedical applications remains challenging. Herein, we demonstrate the potential to overcome several key limitations of traditional FET sensors by exploiting bioactive hydrogels as the gate material. Spatially defined photopolymerization is utilized to achieve selective patterning of polyethylene glycol on top of individual graphene FET devices, through which multiple biospecific receptors can be independently encapsulated into the hydrogel gate. The hydrogel-mediated integration of penicillinase was demonstrated to effectively catalyze enzymatic reaction in the confined microenvironment, enabling real time, label-free detection of penicillin down to 0.2 mM. Multiplexed functionalization with penicillinase and acetylcholinesterase has been demonstrated to achieve highly specific sensing. In addition, the microenvironment created by the hydrogel gate has been shown to significantly reduce the nonspecific binding of nontarget molecules to graphene channels as well as preserve the encapsulated enzyme activity for at least one week, in comparison to free enzymes showing significant signal loss within one day. This general approach presents a new biointegration strategy and facilitates multiplex detection of bioanalytes on the same platform, which could underwrite new advances in healthcare research.

Long-term work quality of patients with mild traumatic brain injury: The associations with postconcussion symptoms.

Return to work (RTW) has always been a determinant functional outcome in patients with mild traumatic brain injury (MTBI). However, the quality of long-term RTW was still unclear. This study thus aims to examine long-term work quality and to reveal its associating factors. A total of 110 patients with MTBI was prospectively recruited. Post-concussion symptoms (PCS) and RTW were evaluated by the Checklist of Post-Concussion Symptoms (CPCS) and Work Quality Index (WQI) respectively at one-week and long-term evaluation (M = 2.90 years, SD = 1.29) post-injury. Only 16% of patients can successfully RTW at one-week post-injury, while 69% of patients have retained their jobs at long-term evaluations. Importantly, 12% of patients had to work under the adverse impacts of PCS at one-week after MTBI, and long-term WQI was significantly associated with PCS at one-week post-injury. Almost 1/3 of patients still had unfavorable long-term work quality even though they could return to work. Thus, a careful evaluation of the early PCS endorsement and work quality for patients with MTBI is merited.

Self-Assembled Biohybrid: A Living Material To Bridge the Functions between Electronics and Multilevel Biological Modules/Systems.

Exoelectrogens are known to be specialized in reducing various extracellular electron acceptors to form conductive nanomaterials that are integrated with their cell bodies both structurally and functionally. Utilizing this unique capacity, we created a strategy toward the design and fabrication of a biohybrid electronic material by exploiting bioreduced graphene oxide (B-rGO) as the structural and functional linker to facilitate the interaction between the exoelectrogen community and external electronics. The metabolic functions of exoelectrogens encoded in this living hybrid can therefore be effectively translated toward corresponding microbial fuel cell applications. Furthermore, this material can serve as a fundamental building block to be integrated with other microorganisms for constructing various electronic components. Toward a broad impact of this biohybridization strategy, photosynthetic organelles and cells were explored to replace exoelectrogens as the active bioreducing components and as formed materials exhibited 4- and 8-fold improvements in photocurrent intensities as compared with native bioelectrode interfaces. Overall, a biologically driven strategy for the fabrication and assembly of electronic materials is demonstrated, which provides a unique opportunity to precisely probe and modulate desired biofunctions through deterministic electronic inputs/outputs and revolutionize the design and manufacturing of next-generation (bio)electronics.

Hydrogel facilitated bioelectronic integration.

The recent advances in bio-integratable electronics are creating new opportunities for investigating and directing biologically significant processes, yet their performance to date is still limited by the inherent physiochemical and signaling mismatches at the heterogeneous interfaces. Hydrogels represent a unique category of materials to bridge the gap between biological and electronic systems because of their structural/functional similarity to biological tissues and design versatility to accommodate cross-system communication. In this review, we discuss the latest progress in the engineering of hydrogel interfaces for bioelectronics development that promotes (1) structural compatibility, where the mechanical and chemical properties of hydrogels can be modulated to achieve coherent, chronically stable biotic-abiotic junctions; and (2) interfacial signal transduction, where the charge and mass transport within the hydrogel mediators can be rationally programmed to condition/amplify the bioderived signals and enhance the electrical/electrochemical coupling. We will further discuss the application of functional hydrogels in complex physiological environments for bioelectronic integration across different scales/biological levels. These ongoing research efforts have the potential to blur the distinction between living systems and artificial electronics, and ultimately decode and regulate biological functioning for both fundamental inquiries and biomedical applications.

Long-Term Presentation of Postconcussion Symptoms and Associated Factors: Analysis of Latent Class Modeling.

OBJECTIVE: Postconcussion symptoms (PCS) are commonly reported by patients with mild traumatic brain injury (MTBI). Although PCS significantly recovered by 3-month postinjury, a number of patients still experienced persistent PCS for >1 year. As few researchers investigated long-term PCS endorsement, the present study thus aims to show the latent structure of long-term PCS and further uncover its associating factors. METHODS: In total, 110 patients with MTBI and 32 healthy participants were prospectively enrolled. PCS was evaluated at 2 weeks and long-term evaluations (mean = 2.90 years) after MTBI. In addition, cognitive functions, which include memory, executive function, and information processing, and emotional disturbances, which include depression, anxiety, and irritability, were also examined at 2-week postinjury. RESULTS: Patients reported significantly more PCS at 2-week postinjury than healthy participants did, but PCS significantly improved at long-term evaluations when comparing with PCS at acute stage after MTBI. Both of PCS at 2 weeks and long-term evaluations can be further subdivided into subgroups based on the severity of PCS, in which specific PCS (e.g., fatigue, loss of energy, insomnia, slowness of information processing, irritability, and blurred vision) can be well differentiated among subgroups at long-term evaluations. CONCLUSIONS: This study directly showed the characteristics of long-term PCS and associating factors. It further evidenced that specific physical, cognitive, and emotional symptoms might be determinant to identify the subgroups of patients with long-term PCS endorsement.

Bottom-Up Construction of Electrochemically Active Living Filters: From Graphene Oxide Mediated Formation of Bacterial Cables to 3D Assembly of Hierarchical Architectures.

Living composites comprising of both biotic and abiotic modules are shifting the paradigm of materials science, yet challenges remain in effectively converging their distinctive structural and functional attributes. Here we present a bottom-up hybridization strategy to construct functionally coherent, electrochemically active biohybrids with optimal mass/charge transport, mechanical integrity, and biocatalytic performance. This biohybrid can overcome several key limitations of traditional biocarrier designs and demonstrate superior efficiency in metabolizing low-concentration toxic ions with minimal environmental impact. Overall, this work exemplifies a biointegration strategy that complements existing synthetic biology toolsets to further expand the range of material attributes and functionalities.

3D Printing of Silk Protein Structures by Aqueous Solvent-Directed Molecular Assembly.

Hierarchical molecular assembly is a fundamental strategy for manufacturing protein structures in nature. However, to translate this natural strategy into advanced digital manufacturing like three-dimensional (3D) printing remains a technical challenge. This work presents a 3D printing technique with silk fibroin to address this challenge, by rationally designing an aqueous salt bath capable of directing the hierarchical assembly of the protein molecules. This technique, conducted under aqueous and ambient conditions, results in 3D proteinaceous architectures characterized by intrinsic biocompatibility/biodegradability and robust mechanical features. The versatility of this method is shown in a diversity of 3D shapes and a range of functional components integrated into the 3D prints. The manufacturing capability is exemplified by the single-step construction of perfusable microfluidic chips which eliminates the use of supporting or sacrificial materials. The 3D shaping capability of the protein material can benefit a multitude of biomedical devices, from drug delivery to surgical implants to tissue scaffolds. This work also provides insights into the recapitulation of solvent-directed hierarchical molecular assembly for artificial manufacturing.