Abstract: A ferrofluidic fluid assay device uses swarm of millimeter-sized magnets was employed as mobile robotic agents (“ferrobots”) for precise and robust handling of magnetized sample droplets and high-fidelity delivery of flexible assay workflows. Within a palm-sized printed circuit board-based programmable platform a myriad of sample handling and bioanalytical operations involved in pooled testing can be performed. This automated technology was applied using the loop-mediated isothermal amplification and detection of SARS-COV-2 virus in clinical samples, where the test results completely matched those obtained off-chip. This technology is easily manufacturable and distributable, and its adoption for viral testing could lead to a 10 to 300-fold reduction in reagent costs, and three orders of magnitude reduction in instrumentation cost. Multiplexed assays may also be performed on a single device.

Abstract: Active biofluid management may be advantageous to the realization of wearable bioanalytical platforms that can autonomously provide frequent, real-time, and accurate measures of biomarkers in epidermally-retrievable biofluids (e.g., sweat). Accordingly, exemplary implementations include a programmable epidermal microfluidic valving system capable of biofluid sampling, routing, and compartmentalization for biomarker analysis. An exemplary system includes a network of individually-addressable microheater-controlled thermo-responsive hydrogel valves, augmented with a pressure regulation mechanism to accommodate pressure built-up, when interfacing sweat glands. The active biofluid control achieved by this system may be harnessed to create unprecedented wearable bioanalytical capabilities at both the sensor level (decoupling the confounding influence of flow rate variability on sensor response) and the system level (facilitating context-based sensor selection/protection).

Abstract: The present embodiments relate to a multimodal cryptographic bio-human machine interface (“CB-HMI”), which seamlessly translates the user's touch-based entries into encrypted biochemical, biophysical, and biometric indices. The CB-HMI features thin hydrogel-coated chemical sensors and inference algorithms to non-invasively and inconspicuously acquire biochemical indices such as circulating molecules that partition onto the skin (here, ethanol and acetaminophen). Additionally, the CB-HMI hosts physical sensors and associated algorithms to simultaneously acquire the user's heart rate, blood oxygen level, and fingerprint minutiae pattern. Additional or alternative embodiments include a touch-based non-invasive monitoring solution for lithium pharmacotherapy management. The system is constructed based on a thin organohydrogel-coated lithium ion-selective electrode (TOH-ISE), where the TOH coating was engineered to render stabilized conditions for sensing.

Abstract: Advancing electronics to interact with tissue necessitates meeting material constraints in electrochemical, electrical, and mechanical domains, simultaneously. Clinical bioelectrodes with established electrochemical functionalities are rigid and mechanically-mismatched with tissue. While conductive materials with tissue-like softness/stretchability are demonstrated, when applied to electrochemically probe tissue, their performance is distorted by strain and corrosion. Here, presented is a layered-architectural composite design, which couples strain-induced cracked films with a strain-isolated out-of-plane conductive pathway and in-plane nanowire networks, to eliminate strain effects on the device electrochemical performance. Accordingly, a library of stretchable, highly conductive, and strain-insensitive bioelectrodes is provided featuring clinically-established brittle interfacial materials (iridium-oxide, gold, platinum, carbon).

Abstract: Example implementations include a method of manufacturing a biochemical sensor by forming a fluid conduit in a microfluidic layer, forming an electrode on an electrode layer, forming a biochemical sensor on the electrode layer, bonding the electrode layer to a first surface of the microfluidic layer, and bonding a barrier layer to a second surface of the microfluidic layer. Example implementations also include a method of electrically detecting a biochemical by contacting an electrode array to a biological surface, obtaining a biofluid at the electrode array from the biological surface, obtaining a response current associated with the biofluid at the electrode array, and generating a quantitative biochemical response based at least partially on the response current. Example implementations further include applying a current to the biological surface. Example implementations further include filtering electrical interference at the electrode array.

Abstract: An electronically-controlled digital ferrofluidic device is disclosed which employs a network of individually addressable coils in conjunction with one or more movable permanent magnets, where each moveable permanent magnet delivers the designated fluid manipulation-based tasks. The underlying mechanism facilitating fluidic operations is realized by addressable electromagnetic actuation of miniaturized mobile magnets that exert localized magnetic body forces on droplets filled with magnetic nanoparticles. The reconfigurable, contactless, and non-interfering magnetic-field operation properties of the underlying actuation mechanism allow for the integration of passive and active components to implement advanced and diverse operations with high efficiency (e.g., droplet sorting, dispensing, generation, merging, mixing, filtering, and analysis).

Abstract: An electronically-controlled digital ferrofluidic device is disclosed which employs a network of individually addressable coils in conjunction with one or more movable permanent magnets, where each moveable permanent magnet delivers the designated fluid manipulation-based tasks. The underlying mechanism facilitating fluidic operations is realized by addressable electromagnetic actuation of miniaturized mobile magnets that exert localized magnetic body forces on droplets filled with magnetic nanoparticles. The reconfigurable, contactless, and non-interfering magnetic-field operation properties of the underlying actuation mechanism allow for the integration of passive and active components to implement advanced and diverse operations with high efficiency (e.g., droplet sorting, dispensing, generation, merging, mixing, filtering, and analysis).

Abstract: A wearable device for multiplexed sweat analysis includes a sensing module. The sensing module includes multiple compartments, including a first compartment configured to induce sweat and sense a target analyte, and a second compartment configured to induce sweat and sense the target analyte.

Abstract: The present embodiments relate generally to an aptamer microneedle patch (“AMPatch”) for providing an example approach to wearable therapeutic drug monitoring (TDM). For example, some embodiments relate to a simple and low-cost EAB-on-microneedle fabrication scheme to develop an AMPatch for in-situ ISF biomonitoring. In some embodiments, a fabrication scheme centers on engineering a gold nanoparticle (AuNP) coating via a single deposition step, which uniquely transforms a clinically-validated needle into a high-quality gold working electrode substrate for strong and compact aptamer immobilization.

Abstract: The present embodiments relate to a multimodal cryptographic bio-human machine interface (“CB-HMI”), which seamlessly translates the user's touch-based entries into encrypted biochemical, biophysical, and biometric indices. The CB-HMI features thin hydrogel-coated chemical sensors and inference algorithms to non-invasively and inconspicuously acquire biochemical indices such as circulating molecules that partition onto the skin (here, ethanol and acetaminophen). Additionally, the CB-HMI hosts physical sensors and associated algorithms to simultaneously acquire the user's heart rate, blood oxygen level, and fingerprint minutiae pattern. Additional or alternative embodiments include a touch-based non-invasive monitoring solution for lithium pharmacotherapy management. The system is constructed based on a thin organohydrogel-coated lithium ion-selective electrode (TOH-ISE), where the TOH coating was engineered to render stabilized conditions for sensing.

Abstract: Wearable technologies for personalized monitoring require sensors that track biomarkers often present at low levels. Cortisol—a key stress biomarker—is present in sweat at low nanomolar concentrations. Previous wearable sensing systems are limited to analytes in the micromolar-millimolar ranges. To overcome these and other limitations, the present embodiments include a flexible field-effect transistor (FET) biosensor array that exploits a new cortisol aptamer coupled to nanometer-thin-film In2O3 FETs. Cortisol levels were determined via molecular recognition by aptamers where binding was transduced to electrical signals on FETs. The physiological relevance of cortisol as a stress biomarker was demonstrated by tracking salivary cortisol levels in participants in a Trier Social Stress Test and establishing correlations between cortisol in diurnal saliva and sweat samples.

Abstract: Example implementations include a method of manufacturing a biochemical sensor by forming a fluid conduit in a microfluidic layer, forming an electrode on an electrode layer, forming a biochemical sensor on the electrode layer, bonding the electrode layer to a first surface of the microfluidic layer, and bonding a barrier layer to a second surface of the microfluidic layer. Example implementations also include a method of electrically detecting a biochemical by contacting an electrode array to a biological surface, obtaining a biofluid at the electrode array from the biological surface, obtaining a response current associated with the biofluid at the electrode array, and generating a quantitative biochemical response based at least partially on the response current. Example implementations further include applying a current to the biological surface. Example implementations further include filtering electrical interference at the electrode array.

Abstract: Example implementations include a method of applying a voltage pulse having a magnitude within a biochemical voltage window associated a biochemical, obtaining a response current from a biochemical sensor electrode, generating a biochemical response voltammogram based on the response current, extracting a current peak from the biochemical response voltammogram, and generating a biochemical concentration based on the current peak. Example implementations further include a method of applying a differential pulse sequence including the voltage pulse to the reference electrode. Example implementations further include a method of applying the differential pulse sequence further comprises applying the differential pulse sequence to the reference electrode at an increasing voltage step.

Abstract: An electronically-controlled digital ferrofluidic device is disclosed which employs a network of individually addressable coils in conjunction with one or more movable permanent magnets, where each moveable permanent magnet delivers the designated fluid manipulation-based tasks. The underlying mechanism facilitating fluidic operations is realized by addressable electromagnetic actuation of miniaturized mobile magnets that exert localized magnetic body forces on droplets filled with magnetic nanoparticles. The reconfigurable, contactless, and non-interfering magnetic-field operation properties of the underlying actuation mechanism allow for the integration of passive and active components to implement advanced and diverse operations with high efficiency (e.g., droplet sorting, dispensing, generation, merging, mixing, filtering, and analysis).

Abstract: Example implementations also include a method of sensing the presence and quantity of a biochemical by applying a current across a biochemical sensing electrode and a reference electrode, contacting a hydrogel layer to a biological surface, absorbing a biofluid from the biological surface into the hydrogel layer, obtaining, at a processor coupled to the biochemical sensing electrode and the reference electrode, a change in current across the biochemical sensing electrode and the reference electrode, and generating, at the processor, a quantitative biochemical response. Example implementations further include obtaining a biometric encryption key based on the biological surface, and encrypting the quantitative response based on a biometric encryption key.

Abstract: Active biofluid management may be advantageous to the realization of wearable bioanalytical platforms that can autonomously provide frequent, real-time, and accurate measures of biomarkers in epidermally-retrievable biofluids (e.g., sweat). Accordingly, exemplary implementations include a programmable epidermal microfluidic valving system capable of biofluid sampling, routing, and compartmentalization for biomarker analysis. An exemplary system includes a network of individually-addressable microheater-controlled thermo-responsive hydrogel valves, augmented with a pressure regulation mechanism to accommodate pressure built-up, when interfacing sweat glands. The active biofluid control achieved by this system may be harnessed to create unprecedented wearable bioanalytical capabilities at both the sensor level (decoupling the confounding influence of flow rate variability on sensor response) and the system level (facilitating context-based sensor selection/protection).

Abstract: Example implementations include a device with an electrode electrically responsive to presence of a biochemical present within a biofluid, and one or more biofouling and interferent mitigation layers disposed on the electrode to block transmission of biofouling agents to the electrode and the reaction of interferents on the electrode. Example implementations also include a method of obtaining a biofluid sample, mitigating a biofouling characteristic associated with the biofluid sample, and obtaining a biochemical characteristic associated with the biofluid sample.

Abstract: A wearable device for biofluid analysis includes a set of sensing electrodes, and the set of sensing electrodes includes a working electrode which includes: (1) abase electrode including a sensing surface; (2) capture probes immobilized on the sensing surface; and (3) a protective layer e disposed on the sensing surface and including a redox couple within the protective layer.

Abstract: A disposable sensor for biofluid analysis includes: (1) a conductive film having a first major surface and a second major surface opposite to the first major surface; (2) a sensing layer disposed on the first major surface of the conductive film; and (3) an adhesive layer disposed on the second major surface of the conductive film.

Abstract: Example implementations include a method of manufacturing a biochemical sensor by forming a fluid region in a microfluidic layer, forming a reference electrode on a planar surface of an electrode layer, forming a biochemical sensor electrode on the planar surface, forming a selective membrane on the biochemical sensor electrode, forming an enzymatic material including a biochemical sensing material on the selective membrane, and bonding the electrode layer to the microfluidic layer. Example implementations also include a device with a reference electrode disposed on a planar surface of an electrode layer, a biochemical sensor electrode disposed on the planar surface, a selective membrane disposed on the biochemical sensor electrode and impermeable to at least one biochemical interferent, and an enzymatic layer disposed on the selective membrane and electrically responsive to a biochemical.