The development of new methods for direct viral detection using streamlined and ideally reagent-free assays is a timely and important, but challenging, problem. The challenge of combatting the COVID-19 pandemic has been exacerbated by the lack of rapid and effective methods to identify viral pathogens like SARS-CoV-2 on-demand. Existing gold standard nucleic acid-based approaches require enzymatic amplification to achieve clinically relevant levels of sensitivity and are not typically used outside of a laboratory setting. Here, we report reagent-free viral sensing that directly reads out the presence of viral particles in 5 minutes using only a sensor-modified electrode chip. The approach relies on a class of electrode-tethered sensors bearing an analyte-binding antibody displayed on a negatively charged DNA linker that also features a tethered redox probe. When a positive potential is applied, the sensor is transported to the electrode surface. Using chronoamperometry, the presence of viral particles and proteins can be detected as these species increase the hydrodynamic drag on the sensor. This report is the first virus-detecting assay that uses the kinetic response of a probe/virus complex to analyze the complexation state of the antibody. We demonstrate the performance of this sensing approach as a means to detect, within 5 min, the presence of the SARS-CoV-2 virus and its associated spike protein in test samples and in unprocessed patient saliva.

The ability to sense biological inputs using self-contained devices unreliant on external reagents or reporters would open countless opportunities to collect information about our health and environment. Currently, a very limited set of molecular inputs can be detected using this type of sensor format. The development of versatile reagentless sensors that could track molecular analytes in biological fluids remains an unmet need. Here, we describe a new universal sensing mechanism that is compatible with the analysis of proteins that are important physiological markers of stress, allergy, cardiovascular health, inflammation and cancer. The sensing mechanism we developed is based on the measurement of field-induced directional diffusion of a nanoscale molecular pendulum tethered to an electrode surface and the sensitivity of electrontransfer reaction kinetics to molecular size. Using time-resolved electrochemical measurements of diffusional motion, the presence of an analyte bound to a sensor complex can be continuously tracked in real time. We show that this sensing approach is compatible with making measurements in blood, saliva, urine, tears and sweat and that the sensors can collect data in situ in living animals. The sensor platform described enables a broad range of applications in personalized health monitoring.

Nanostructured materials can now be engineered with great precision and complexity as a result of advances in design and fabrication, and offer distinct advantages in many biosensing and biomedical applications. The materials most widely used in this field are semiconductors and noble metals. Each offers multiple length scales of nanostructuring that program their physicochemical properties for different biosensing applications. Here, nanostructured materials and their applications are reviewed together with semiconductors and noble metals, as well as hybrid materials that unite these two classes—all with the goal of linking performance characteristics to applications in biomedicine.

Reagent-free electronic biosensors capable of analyzing disease markers directly in unprocessed body fluids will enable the development of simple & affordable devices for personalized healthcare monitoring.Here we report a powerful and versatile nucleic acidbased reagent-free electronic sensing system. The signal transduction is based on the kinetics of an electrodetethered molecular pendulum-a rigid double stranded DNA with one of the strands displaying an analytebinding aptamer and the other featuring a redox probe -that exhibits field-induced transport modulated by receptor occupancy. Using chronoamperometry, which enables the sensor to circumvent the conventional Debye length limitation, the binding of an analyte can be monitored as these species increase the hydrodynamic drag. The sensing platform demonstrates a low femtomolar quantification limit and minimal crossreactivity in analyzing cardiac biomarkers in whole blood collected from patients with chronic heart failure.The decentralization of molecular diagnostics from clinical laboratories to the point-of-need has the potential to significantly impact the daily lives of patients and empower them to live healthier lives. [1] While sophisticated, highthroughput laboratory-based approaches provide accurate and actionable results, the analytical process is complex, laborious, expensive, and often inaccessible to non-specialist end users. [1] These limitations have undermined the true potential of precision and personalized healthcare models, which promise to replace traditional trial-and-error based clinical practices with data-driven, patient-specific treatment plans. [1] Progress towards these goals has been made over the last decade, but there remains a major technology lag towards individualizing patient treatment. [1h] The development of reagent-free self-contained electronic bioanalytical systems in recent years has reignited the quest for precision medicine by generating patient-specific data in real time. Unfortunately, a major bottleneck of these emerging devices is the lack of powerful biomolecular detectors with autonomous functionality for monitoring disease markers directly in unprocessed body fluids. [1c] Chip-based reagent-free electrochemical approaches are ideal candidates for building fully integrated handheld, wearable, and implantable type bioelectronic testing devices that can be employed anywhere with optimal user friendliness. [2] Several detectors based on the structural switching of DNA aptamers and other DNA-based structures containing recognition elements have been applied broadly to reagent-free biomolecular analysis. [2] However, most of these affinity-based electronic biomolecular sensors suffer from the conventional Debye length limitation. [3c,d] The signal transduction efficiency of these electronic biosensors drops substantially in complex biological samples due to the shielding created by the electrical double layer at the electrode-electrolyte interface, which leads to compromised sensitivity (hundreds of nanomolar ...

The development of robust biosensing strategies that can be easily implemented in everyday life remains a challenge for the future of modern biosensor research. While several reagentless approaches have attempted to address this challenge, they often achieve user-friendliness through sacrificing sensitivity or universality. While acceptable for certain applications, these trade-offs hinder the widespread adoption of reagentless biosensing technologies. Here, we report a novel approach to reagentless biosensing that achieves high sensitivity, rapid detection, and universality using the SARS-CoV-2 virus as a model target. Universality is achieved by using nanoscale molecular pendulums, which enables reagentless electrochemical biosensing through a variable antibody recognition element. Enhanced sensitivity and rapid detection are accomplished by incorporating the coffee-ring phenomenon into the sensing scheme, allowing for target preconcentration on a ring-shaped electrode. Using this approach, we obtained limits of detection of 1 fg/mL and 20 copies/mL for the SARS-CoV-2 nucleoproteins and viral particles, respectively. In addition, clinical sample analysis showed excellent agreement with Ct values from PCR-positive SARS-CoV-2 patients.

Retinal stem cells (RSCs) are promising candidates for patient-derived cell therapy to repair damage to the eye; however, RSCs are rare in retinal samples and lack validated markers, making cell sorting a significant challenge. Here we report a high-resolution deterministic lateral displacement microfluidic device that profiles RSCs in distinct size populations. Only by developing a chip that promotes cell tumbling do we limit cell deformation through apertured channels and thereby increase the size-sorting resolution of the device. We systematically explore a spectrum of microstructures, including optimized notched pillars, to study and then rationally promote cell tumbling. We find that RSCs exhibit larger diameters than most ciliary epithelial cells, an insight into RSC morphology that allows enrichment from biological samples.

Previous studies of magnetoreception in honey bees, Apis mellifera, focused on the identification of magnetic material, its formation, the location of the receptor and potential underlying sensory mechanisms, but never directly linked magnetic material to a magnetoreceptive function. In our study, we demonstrate that ferromagnetic material consistent with magnetite plays an integral role in the bees' magnetoreceptor. Subjecting lyophilized and pelletized bee tagmata to analyses by a superconducting quantum interference device generated a distinct hysteresis loop for the abdomen but not for the thorax or the head of bees, indicating the presence of ferromagnetic material in the bee abdomen. Magnetic remanence of abdomen pellets produced from bees that were, or were not, exposed to the 2.2-kOe field of a magnet while alive differed, indicating that magnet exposure altered the magnetization of this magnetite in live bees. In behavioural two-choice field experiments, bees briefly exposed to the same magnet, but not sham-treated control bees, failed to sense a custom-generated magnetic anomaly, indicating that magnet exposure had rendered the bees' magnetoreceptor dysfunctional. Our data support the conclusion that honey bees possess a magnetite-based magnetoreceptor located in the abdomen.

The ability to sense biological inputs using self-contained devices unreliant on external reagents or reporters would open countless opportunities to collect information about our health and environment. Currently, a very limited set of molecular inputs can be detected using this type of sensor format. The development of versatile reagentless sensors that could track molecular analytes in biological fluids remains an unmet need. Here, we describe a new universal sensing mechanism that is compatible with the analysis of proteins that are important physiological markers of stress, allergy, cardiovascular health, inflammation and cancer. The sensing mechanism we developed is based on the measurement of field-induced directional diffusion of a nanoscale molecular pendulum tethered to an electrode surface and the sensitivity of electrontransfer reaction kinetics to molecular size. Using time-resolved electrochemical measurements of diffusional motion, the presence of an analyte bound to a sensor complex can be continuously tracked in real time. We show that this sensing approach is compatible with making measurements in blood, saliva, urine, tears and sweat and that the sensors can collect data in situ in living animals. The sensor platform described enables a broad range of applications in personalized health monitoring.