Electrochemical impedance spectroscopy in vivo for neurotechnology and bioelectronics
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An ingestible bioimpedance sensing device for wireless monitoring of epithelial barriers
Existing gastrointestinal (GI) diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus. In the GI tract, local inflammatory processes induce alterations in tight junction proteins, enhancing paracellular ion permeability. Although transepithelial electrical resistance (TEER) may be used in the laboratory to assess mucosal barrier integrity, there are no existing methodologies for characterizing tight junction dilation in vivo. Addressing this technology gap, intraluminal bioimpedance sensing may be employed as a localized, non-invasive surrogate to TEER electrodes used in cell cultures. Thus far, bioimpedance has only been implemented in esophagogastroduodenoscopy (EGD) due to the need for external electronics connections. In this work, we develop a novel, noise-resilient Bluetooth-enabled ingestible device for the continuous, non-invasive measurement of intestinal mucosal “leakiness.” As a proof-of-concept, we validate wireless impedance readout on excised porcine tissues in motion. Through an animal study, we demonstrate how the device exhibits altered impedance response to tight junction dilation induced on mice colonic tissue through calcium-chelator exposure. Device measurements are validated using standard benchtop methods for assessing mucosal permeability.
Acoustic impedance-based surface acoustic wave chip for gas leak detection and respiratory monitoring
Acoustic impedance enables many interesting acoustic applications. However, acoustic impedance for gas sensing is rare and difficult. Here we introduce a micro-nano surface acoustic wave (SAW) chip based on the acoustic impedance effect to achieve ultra-fast and wide-range gas sensing. We theoretically established the relationship between surface load acoustic impedance and SAW attenuation, and analyzed the influence of acoustic impedance on acoustic propagation loss under different gas/humidity media. Experimental measurements reveal that the differences in acoustic impedance generated by different gases trigger different acoustic attenuation, and can achieve wide-range (0–100 v/v%) gas monitoring, with ultra-fast response and recovery speeds reaching sub-second levels (t90 < 1 s, t10 < 0.5 s) and detection limit of ~1 v/v%. This capability can also be perfectly utilized for human respiratory monitoring, accurately reflecting respiratory status, frequency, and intensity. Consequently, the SAW chip based on the acoustic impedance effect provides a new solution for in-situ detection of gas leaks and precise monitoring of human respiration.
Transparent, flexible graphene–ITO-based neural microelectrodes for simultaneous electrophysiology recording and calcium imaging of intracortical neural activity in freely moving mice
To understand the complex dynamics of neural activity in the brain across various temporal and spatial scales, it is crucial to record intracortical multimodal neural activity by combining electrophysiological recording and calcium imaging techniques. This poses significant constraints on the geometrical, mechanical, and optical properties of the electrodes. Here, transparent flexible graphene–ITO-based neural microelectrodes with small feature sizes are developed and validated for simultaneous electrophysiology recording and calcium imaging in the hippocampus of freely moving mice. A micro-etching technique and an oxygen plasma pre-treating method are introduced to facilitate large-area graphene transfer and establish stable low-impedance contacts between graphene and metals, leading to the batch production of high-quality microelectrodes with interconnect widths of 10 μm and recording sites diameters of 20 μm. These electrodes exhibit appropriate impedance and sufficient transparency in the field of view, enabling simultaneous recording of intracortical local field potentials and even action potentials along with calcium imaging in freely moving mice. Both types of electrophysiological signals are found to correlate with calcium activity. This proof-of-concept work demonstrates that transparent flexible graphene–ITO-based neural microelectrodes are promising tools for multimodal neuroscience research.
Bipolar electrochemistry-driven wireless drug loading and energy harvesting in conductive hybrid hydrogels
Bipolar electrochemistry enables wireless and spatially controlled redox reactions on (semi)conductive objects immersed in an electrolyte. Here, we investigate advanced bipolar electrochemistry applications using flexible bipolar electrodes coated with hybrid films of conductive polymer poly(3,4-ethylenedioxythiophene) and alginate hydrogels. These coatings allow for the wireless creation of reversible redox and chemical gradients, providing targeted drug loading and energy harvesting opportunities. We use cyclic voltammetry, electrochemical impedance spectroscopy, Raman microscopy, and X-ray photoelectron spectroscopy to characterize distinct redox regions within the bipolar electrode. The wireless and selective loading of a model drug, fluorescein, into the hydrogel, demonstrated control over drug distribution, suggesting an alternative to conventional uniform doping techniques. Furthermore, cutting the gradient-encoded bipolar electrode and closing an external circuit between the halves, enables energy recovery through a concentration cell mechanism. Our findings illustrate the potential of bipolar electrochemistry in creating versatile platforms that bridge materials science, electrochemistry, and bioelectronics for innovative biomedical and energy applications.
Antibody-functionalized MXene-based electrochemical biosensor for point-of-care detection of vitamin D deficiency
Clinical studies routinely show that individuals suffer from vitamin D deficiency, which can result in health complications that include cardiovascular disease, autoimmune disorders, neurodegenerative diseases, and different skeletal deformities. Given its integral role in homeostasis and connection to many pathologies, early diagnosis of vitamin D deficiency is crucial. However, monitoring vitamin D levels is challenging, particularly in remote regions, due to the cost, time, and complexity of existing methods. Here, we develop an electrochemical biosensor for vitamin D based on antibody-functionalized MXenes, offering clinically relevant sensitivity, specificity, and amenability for point-of-care testing. Ti3C2Tx MXene nanosheets are amine-functionalized by electrostatically-driven modification with polyethylenimine, whose functionalities are then used for covalent conjugation of anti-vitamin D antibodies via glutaraldehyde chemistry. This platform achieves a detection limit of 1 pg mL−1 with a dynamic range (0.1–500 ng mL−1) that covers clinically relevant deficiency, insufficiency, sufficiency, and toxicity.
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