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Congestive heart failure (CHF) is a fatal disease with progressive severity and no cure; the hearts inability to adequately pump blood leads to fluid accumulation and frequent hospital readmissions after initial treatments. Therefore, it is imperative to continuously monitor CHF patients during its early stages to slow its progression and enable timely medical interventions for optimal treatment. An increase in interstitial fluid pressure (IFP) is indicative of acute CHF exacerbation, making IFP a viable biomarker for predicting upcoming CHF if continuously monitored. In this paper, we present an inductor-capacitor (LC) sensor for subcutaneous wireless and continuous IFP monitoring. The sensor is composed of inexpensive planar copper coils defined by a simple craft cutter, which serves as both the inductor and capacitor. Because of its sensing mechanism, the sensor does not require batteries and can wirelessly transmit pressure information. The sensor has a low-profile form factor for subcutaneous implantation and can communicate with a readout device through 4 layers of skin (12.7 mm thick in total). With a soft silicone rubber as the dielectric material between the copper coils, the sensor demonstrates an average sensitivity as high as -8.03 MHz/mmHg during in vitro simulations.

The human body exhibits complex, spatially distributed chemo-electro-mechanical processes that must be properly captured for emerging applications in virtual/augmented reality, precision health, activity monitoring, bionics, and more. A key factor in enabling such applications involves the seamless integration of multipurpose wearable sensors across the human body in different environments, spanning from indoor settings to outdoor landscapes. Here, we report a versatile epidermal body area network ecosystem that enables wireless power and data transmission to and from battery-free wearable sensors with continuous functionality from dry to underwater settings. This is achieved through an artificial near field propagation across the chain of biocompatible, magneto-inductive metamaterials in the form of stretchable waterborne skin patches-these are fully compatible with pre-existing consumer electronics. Our approach offers uninterrupted, self-powered communication for human status monitoring in harsh environments where traditional wireless solutions (such as Bluetooth, Wi-Fi or cellular) are unable to communicate reliably.

A phenylboronic acid-based, hydrogel-interlayer Radio-Frequency (RF) resonator is demonstrated as a highly-responsive, passive and wireless sensor for glucose monitoring. Constructs are composed of unanchored, capacitively-coupled split rings interceded by glucose-responsive hydrogels. Phenylboronic acid-hydrogels exhibit volumetric and dielectric variations in response to environmental glucose concentrations-these are efficiently converted to large shifts in the resonant response of interlayer-RF sensors. These tiny, stretchable and scalable sensors (5 mm × 5 mm x 250 μm) require no microelectronics or power at the sensing node and can be read-out remotely via near-field coupling. Sensors exhibit high sensitivities (~10% shift in resonant frequency-corresponding to 50 MHz-per 150 mg/dL of glucose), possess a limit of detection of 10 mg/dL, and a step response time of approximately 1 h to abrupt shifts in carbohydrate concentration. Notably, these sensors exhibited no signal drift or hysteresis over the time periods characterized herein (45 days at room temperature). We transform sensors into bioelectronic RF reporter-tags via the attachment of a single LED-these remotely report on glucose concentration via emitted light. We anticipate the non-degradative, long-term nature of both RF read-out and phenylboronic acid-based hydrogels will enable biosensors capable of long-term, remote read-out of glucose.

In the version of this Article originally published, in Fig. 1a, all cells in the top schematic were missing, and in the bottom-left schematic showing multiple pattern shapes, two cells were missing in the bottom-right corner. This figure has now been updated in all versions of the Article.

As cells with aberrant force-generating phenotypes can directly lead to disease, cellular force-generation mechanisms are high-value targets for new therapies. Here, we show that single-cell force sensors embedded in elastomers enable single-cell force measurements with ~100-fold improvement in throughput than was previously possible. The microtechnology is scalable and seamlessly integrates with the multi-well plate format, enabling highly parallelized time-course studies. In this regard, we show that airway smooth muscle cells isolated from fatally asthmatic patients have innately greater and faster force-generation capacity in response to stimulation than healthy control cells. By simultaneously tracing agonist-induced calcium flux and contractility in the same cell, we show that the calcium level is ultimately a poor quantitative predictor of cellular force generation. Finally, by quantifying phagocytic forces in thousands of individual human macrophages, we show that force initiation is a digital response (rather than a proportional one) to the proper immunogen. By combining mechanobiology at the single-cell level with high-throughput capabilities, this microtechnology can support drug-discovery efforts for clinical conditions associated with aberrant cellular force generation.

In this report, we present multiparameter deformability cytometry (m-DC), in which we explore a large set of parameters describing the physical phenotypes of pluripotent cells and their derivatives. m-DC utilizes microfluidic inertial focusing and hydrodynamic stretching of single cells in conjunction with high-speed video recording to realize high-throughput characterization of over 20 different cell motion and morphology-derived parameters. Parameters extracted from videos include size, deformability, deformation kinetics, and morphology. We train support vector machines that provide evidence that these additional physical measurements improve classification of induced pluripotent stem cells, mesenchymal stem cells, neural stem cells, and their derivatives compared to size and deformability alone. In addition, we utilize visual interactive stochastic neighbor embedding to visually map the high-dimensional physical phenotypic spaces occupied by these stem cells and their progeny and the pathways traversed during differentiation. This report demonstrates the potential of m-DC for improving understanding of physical differences that arise as cells differentiate and identifying cell subpopulations in a label-free manner. Ultimately, such approaches could broaden our understanding of subtle changes in cell phenotypes and their roles in human biology.

We introduce a label-free method to rapidly phenotype and classify cells purely based on physical properties. We extract 15 biophysical parameters from cells as they deform in a microfluidic stretching flow field via high-speed microscopy and apply machine-learning approaches to discriminate different cell types and states. When employing the full 15 dimensional dataset, the technique robustly classifies individual cells based on their pluripotency, with accuracy above 95%. Rheological and morphological properties of cells while deforming were critical for this classification. We also show the application of this method in accurate classifying cells based on their viability, drug screening and detecting populations of malignant cells in mixed samples. We show that some of the extracted parameters are not linearly independent, and in fact we reach maximum classification accuracy by using only a subset of parameters. However, the informative subsets could vary depending on cell types in the sample. This work shows the utility of an assay purely based on intrinsic biophysical properties of cells to identify changes in cell state. In addition to a label-free alternative to flow cytometry in certain applications, this work, also can provide novel intracellular metrics that would not be feasible with labeled approaches (i.e. flow cytometry).

Extraction of rare target cells from biosamples is enabling for life science research. Traditional rare cell separation techniques, such as magnetic activated cell sorting, are robust but perform coarse, qualitative separations based on surface antigen expression. A quantitative magnetic separation technology is reported using high-force magnetic ratcheting over arrays of magnetically soft micropillars with gradient spacing, and the system is used to separate and concentrate magnetic beads based on iron oxide content (IOC) and cells based on surface expression. The system consists of a microchip of permalloy micropillar arrays with increasing lateral pitch and a mechatronic device to generate a cycling magnetic field. Particles with higher IOC separate and equilibrate along the miropillar array at larger pitches. A semi-analytical model is developed that predicts behavior for particles and cells. Using the system, LNCaP cells are separated based on the bound quantity of 1 μm anti-epithelial cell adhesion molecule (EpCAM) particles as a metric for expression. The ratcheting cytometry system is able to resolve a ±13 bound particle differential, successfully distinguishing LNCaP from PC3 populations based on EpCAM expression, correlating with flow cytometry analysis. As a proof-of-concept, EpCAM-labeled cells from patient blood are isolated with 74% purity, demonstrating potential toward a quantitative magnetic separation instrument.

A process to surface pattern polydimethylsiloxane (PDMS) with ferromagnetic structures of varying sizes (micrometer to millimeter) and thicknesses (>70 μm) is developed. Their flexibility and magnetic reach are utilized to confer dynamic, additive properties to a variety of substrates, such as coverslips and Eppendorf tubes. It is found that these substrates can generate additional modes of magnetic droplet manipulation, and can tunably steer magnetic-cell organization.

Micro-scale biological tools that have allowed probing of individual cells--from the genetic, to proteomic, to phenotypic level--have revealed important contributions of single cells to direct normal and diseased body processes. In analyzing single cells, sample heterogeneity between and within specific cell types drives the need for high-throughput and quantitative measurement of cellular parameters. In recent years, high-throughput single-cell analysis platforms have revealed rare genetic subpopulations in growing tumors, begun to uncover the mechanisms of antibiotic resistance in bacteria, and described the cell-to-cell variations in stem cell differentiation and immune cell response to activation by pathogens. This review surveys these recent technologies, presenting their strengths and contributions to the field, and identifies needs still unmet toward the development of high-throughput single-cell analysis tools to benefit life science research and clinical diagnostics.

A substrate fabrication process is developed to pattern both the extracellular matrix (ECM) and rigidity at sub-cellular spatial resolution. When growing cells on these substrates, it is found that cells respond locally in their cytoskeleton assembly. The presented method allows unique insight into the biological interpretation of mechanical signals, whereas photolithography-based fabrication is amenable to integration with complex microfabricated substructures.

Micro-patterning tools adopted from the semiconductor industry have mostly been optimized to pattern features onto rigid silicon and glass substrates, however, recently the need to pattern on soft substrates has been identified in simulating cellular environments or developing flexible biosensors. We present a simple method of introducing a variety of patterned materials and structures into ultra-flexible polydimethylsiloxane (PDMS) layers (elastic moduli down to 3 kPa) utilizing water-soluble dextran sacrificial thin films. Dextran films provided a stable template for photolithography, metal deposition, particle adsorption, and protein stamping. These materials and structures (including dextran itself) were then readily transferrable to an elastomer surface following PDMS (10 to 70∶1 base to crosslinker ratios) curing over the patterned dextran layer and after sacrificial etch of the dextran in water. We demonstrate that this simple and straightforward approach can controllably manipulate surface wetting and protein adsorption characteristics of PDMS, covalently link protein patterns for stable cell patterning, generate composite structures of epoxy or particles for study of cell mechanical response, and stably integrate certain metals with use of vinyl molecular adhesives. This method is compatible over the complete moduli range of PDMS, and potentially generalizable over a host of additional micro- and nano-structures and materials.

We report a technique for generating controllable, time-varying and localizable forces on arrays of cells in a massively parallel fashion. To achieve this, we grow magnetic nanoparticle-dosed cells in defined patterns on micromagnetic substrates. By manipulating and coalescing nanoparticles within cells, we apply localized nanoparticle-mediated forces approaching cellular yield tensions on the cortex of HeLa cells. We observed highly coordinated responses in cellular behavior, including the p21-activated kinase-dependent generation of active, leading edge-type filopodia and biasing of the metaphase plate during mitosis. The large sample size and rapid sample generation inherent to this approach allow the analysis of cells at an unprecedented rate: in a single experiment, potentially tens of thousands of cells can be stimulated for high statistical accuracy in measurements. This technique shows promise as a tool for both cell analysis and control.

Textile-based sensors have emerged as a promising technology for enabling low-burden, personalized, and on-body biometrics. However, current textile sensors often lack multimodal or multipositional sensing capabilities, are challenging to fabricate at scale, and are not seamlessly integrated into textile-borne readout systems. We report textile-integrated, laser-induced graphene (LIG) sensors for multiparametric biometrics monitoring. The LIG sensors are designed with custom patterns specific to different stimulistrain, humidity, and temperature demonstrated hereinand exhibit tunable sensitivity through control of the pattern geometry and the laser power used during LIG conversion. These sensors are highly sensitive to changes in resistance, rapidly respond to stimuli (<5 s), and exhibit remarkable stability for at least 1000 cycles. Lastly, such sensors are synthesized alongside magnetic metamaterials and are seamlessly coupled with flexible near-field communication systems directly on textile. This enables fully integrated "smart" clothing capable of battery-free, wireless monitoring of cross-body metrics. Such protocols represent a straightforward, accessible strategy for directly incorporating multiple sensor and network elements into on-demand textiles for advanced human body measurements. [ABSTRACT FROM AUTHOR]

Nutrition measurement has broad applications in science, ranging from dietary assessment, to food monitoring, personalized health, and more. Despite its importance, there are currently no tools that offer continuous cotracking of nutrients direct from food. In this study, the multiscale engineering of silk biopolymer‐interlayer sensors is reported for comonitoring of nutrients. By manipulating various nano‐ to mesostructural properties of such biosensors, sensors are obtained with programmable sensitivity and selectivity to salts, sugars, and oils/fats. Notably, this approach requires no specialized nanomaterials or delicate biomolecules. Programmable biosensors are further formatted for wireless readout and characteristics of these passive, wireless nutrient monitors are studied in vitro. As a proof of concept, the discrimination and comonitoring of salt, sugar, and fat content direct from real, complex foods such as milk, meat, soup, and tea drinks are demonstrated. It is anticipated that such sensors can be utilized in emerging dietary tools for applications across food tracking and human health. In addition, such strategies are expected in structural engineering of sensors to be adaptable to existing or emerging selective or partially selective sensors. [ABSTRACT FROM AUTHOR]

Wearable sensors continually evolve to become more epidermal‐like, yet still face challenges pertaining to conformability and reliance on wires and power sources. Herein, a nontoxic silver conductive ink made from children's school glue is used as a versatile medium for rapid, on‐demand wearable sensor development. This conductive ink can be painted directly onto the skin and to achieve dry electronics with maximal skin contact suitable for electrocardiogram use. Multilayer pressure sensors and near‐field communication (NFC) resonators manufactured using the silver ink demonstrate wireless and battery‐free capabilities for physiological monitoring purposes. [ABSTRACT FROM AUTHOR]