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A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Biosensors and Healthcare".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 37742

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Special Issue Editors

Dr. Grace M. Hwang

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Guest Editor

Applied Physics Laboratory, Johns Hopkins University, Baltimore, MD, USA
Interests: disability and rehabilitation engineering; neuroscience; brain-inspired engineering; neurorobotics

Prof. Dr. Aleksandr Simonian

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Guest Editor

Samuel Ginn College of Engineering, Auburn University, Auburn, WA, USA
Interests: electroanalytical and bioanalytical chemistry; adaptive biosensing systems; bio-functional interfaces

Special Issue Information

Dear Colleagues,

Our understanding of how the brain functions has been improved by advances in modern invasive and noninvasive brain imaging, stimulation, and neuromodulation technologies. Advances in the monitoring, identification and quantification of biological analytes and phenomena using innovations that exist at the intersection of engineering, neuroscience, and information technology have grown at a tremendous pace in the last two decades thanks in part to the brain initiatives around the globe. Understanding the dynamics of neurochemicals (e.g., neuromodulators, neurotransmitters, or ionic concentrations) is essential to understanding brain function, and requires accurate, real-time quantification of brain structures and surrounding environment. This Special Issue invites articles that describe advances in biosensors to accelerate the development of knowledge regarding brain function, and, conversely, advances from insights into how the brain computes and learns to accelerate biosensor design. Having in mind the importance of minimally invasive techniques for monitoring brain chemistry in vivo, we are particularly interested in the development of novel biosensors that can simultaneously measure multiple biological analytes across spatiotemporal scales. We are also interested in brain-inspired biosensor design and the design of novel biosensing systems that will advance biomedical engineering, disability and rehabilitation engineering, neural engineering, neurophotonics, neurorobotics, and other high-impact engineering fields. We encourage papers with experimental results and validation.

Dr. Grace M. Hwang
Prof. Dr. Aleksandr Simonian
Guest Editors

Manuscript Submission Information

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Keywords

brain-inspired
biosensing
neurochemicals
neuromodulators
neuron-glial interactions
neuromorphic computing
neurophotonics
neuroscience

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Published Papers (10 papers)

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Editorial

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8 pages, 220 KiB

Open AccessEditorial

Special Issue—Biosensors and Neuroscience: Is Biosensors Engineering Ready to Embrace Design Principles from Neuroscience?

by Grace M. Hwang and Aleksandr L. Simonian

Biosensors 2024, 14(2), 68; https://doi.org/10.3390/bios14020068 - 29 Jan 2024

Viewed by 1577

Abstract

In partnership with the Air Force Office of Scientific Research (AFOSR), the National Science Foundation’s (NSF) Emerging Frontiers and Multidisciplinary Activities (EFMA) office of the Directorate for Engineering (ENG) launched an Emerging Frontiers in Research and Innovation (EFRI) topic for the fiscal years [...] Read more.

(This article belongs to the Special Issue Biosensors and Neuroscience)

Research

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11 pages, 3273 KiB

Open AccessArticle

Single-Cell Spatial MIST for Versatile, Scalable Detection of Protein Markers

by Arafat Meah, Vadanasundari Vedarethinam, Robert Bronstein, Nehaben Gujarati, Tanya Jain, Sandeep K. Mallipattu, Yueming Li and Jun Wang

Biosensors 2023, 13(9), 852; https://doi.org/10.3390/bios13090852 - 27 Aug 2023

Viewed by 2014

Abstract

High-multiplex detection of protein biomarkers across tissue regions has been an attractive spatial biology approach due to significant advantages over traditional immunohistochemistry (IHC) methods. Different from most methods, spatial multiplex in situ tagging (MIST) transfers the spatial protein expression information to an ultrahigh-density, large-scale MIST array. This technique has been optimized to reach single-cell resolution by adoption of smaller array units and 30% 8-arm PEG polymer as transfer medium. Tissue cell nuclei stained with lamin B have been clearly visualized on the MIST arrays and are colocalized with detection of nine mouse brain markers. Pseudocells defined at 10 μm in size have been used to fully profile tissue regions including cells and the intercellular space. We showcased the versatility of our technology by successfully detecting 20 marker proteins in kidney samples with the addition of five minutes atop the duration of standard immunohistochemistry protocols. Spatial MIST is amenable to iterative staining and detection on the same tissue samples. When 25 proteins were co-detected on 1 mouse brain section for each round and 5 rounds were executed, an ultrahigh multiplexity of 125 proteins was obtained for each pseudocell. With its unique abilities, this single-cell spatial MIST technology has the potential to become an important method in advanced diagnosis of complex diseases. Full article

(This article belongs to the Special Issue Biosensors and Neuroscience)

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13 pages, 2274 KiB

Open AccessArticle

Carbon Electrode Sensor for the Measurement of Cortisol with Fast-Scan Cyclic Voltammetry

by Michelle Hadad, Nadine Hadad and Alexander G. Zestos

Biosensors 2023, 13(6), 626; https://doi.org/10.3390/bios13060626 - 6 Jun 2023

Cited by 4 | Viewed by 3112

Abstract

Cortisol is a vital steroid hormone that has been known as the “stress hormone”, which is elevated during times of high stress and anxiety and has a significant impact on neurochemistry and brain health. The improved detection of cortisol is critically important as it will help further our understanding of stress during several physiological states. Several methods exist to detect cortisol; however, they suffer from low biocompatibility and spatiotemporal resolution, and they are relatively slow. In this study, we developed an assay to measure cortisol with carbon fiber microelectrodes (CFMEs) and fast-scan cyclic voltammetry (FSCV). FSCV is typically utilized to measure small molecule neurotransmitters by producing a readout cyclic voltammogram (CV) for the specific detection of biomolecules on a fast, subsecond timescale with biocompatible CFMEs. It has seen enhanced utility in measuring peptides and other larger compounds. We developed a waveform that scanned from −0.5 to −1.2 V at 400 V/s to electro-reduce cortisol at the surface of CFMEs. The sensitivity of cortisol was found to be 0.87 ± 0.055 nA/μM (n = 5) and was found to be adsorption controlled on the surface of CFMEs and stable over several hours. Cortisol was co-detected with several other biomolecules such as dopamine, and the waveform was fouling resistant to repeated injections of cortisol on the surface of the CFMEs. Furthermore, we also measured exogenously applied cortisol into simulated urine to demonstrate biocompatibility and potential use in vivo. The specific and biocompatible detection of cortisol with high spatiotemporal resolution will help further elucidate its biological significance and further understand its physiological importance and impact on brain health. Full article

(This article belongs to the Special Issue Biosensors and Neuroscience)

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15 pages, 2766 KiB

Open AccessArticle

Cultured Vagal Afferent Neurons as Sensors for Intestinal Effector Molecules

by Gregory Girardi, Danielle Zumpano, Noah Goshi, Helen Raybould and Erkin Seker

Biosensors 2023, 13(6), 601; https://doi.org/10.3390/bios13060601 - 31 May 2023

Cited by 2 | Viewed by 2935

Abstract

The gut–brain axis embodies the bi-directional communication between the gastrointestinal tract and the central nervous system (CNS), where vagal afferent neurons (VANs) serve as sensors for a variety of gut-derived signals. The gut is colonized by a large and diverse population of microorganisms that communicate via small (effector) molecules, which also act on the VAN terminals situated in the gut viscera and consequently influence many CNS processes. However, the convoluted in vivo environment makes it difficult to study the causative impact of the effector molecules on VAN activation or desensitization. Here, we report on a VAN culture and its proof-of-principle demonstration as a cell-based sensor to monitor the influence of gastrointestinal effector molecules on neuronal behavior. We initially compared the effect of surface coatings (poly-L-lysine vs. Matrigel) and culture media composition (serum vs. growth factor supplement) on neurite growth as a surrogate of VAN regeneration following tissue harvesting, where the Matrigel coating, but not the media composition, played a significant role in the increased neurite growth. We then used both live-cell calcium imaging and extracellular electrophysiological recordings to show that the VANs responded to classical effector molecules of endogenous and exogenous origin (cholecystokinin serotonin and capsaicin) in a complex fashion. We expect this study to enable platforms for screening various effector molecules and their influence on VAN activity, assessed by their information-rich electrophysiological fingerprints. Full article

(This article belongs to the Special Issue Biosensors and Neuroscience)

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19 pages, 3648 KiB

Open AccessArticle

In Vitro Biofouling Performance of Boron-Doped Diamond Microelectrodes for Serotonin Detection Using Fast-Scan Cyclic Voltammetry

by Bhavna Gupta, Mason L. Perillo, James R. Siegenthaler, Isabelle E. Christensen, Matthew P. Welch, Robert Rechenberg, G M Hasan Ul Banna, Davit Galstyan, Michael F. Becker, Wen Li and Erin K. Purcell

Biosensors 2023, 13(6), 576; https://doi.org/10.3390/bios13060576 - 25 May 2023

Cited by 5 | Viewed by 2957

Abstract

Neurotransmitter release is important to study in order to better understand neurological diseases and treatment approaches. Serotonin is a neurotransmitter known to play key roles in the etiology of neuropsychiatric disorders. Fast-scan cyclic voltammetry (FSCV) has enabled the detection of neurochemicals, including serotonin, on a sub-second timescale via the well-established carbon fiber microelectrode (CFME). However, poor chronic stability and biofouling, i.e., the adsorption of interferent proteins to the electrode surface upon implantation, pose challenges in the natural physiological environment. We have recently developed a uniquely designed, freestanding, all-diamond boron-doped diamond microelectrode (BDDME) for electrochemical measurements. Key potential advantages of the device include customizable electrode site layouts, a wider working potential window, improved stability, and resistance to biofouling. Here, we present a first report on the electrochemical behavior of the BDDME in comparison with CFME by investigating in vitro serotonin (5-HT) responses with varying FSCV waveform parameters and biofouling conditions. While the CFME delivered lower limits of detection, we also found that BDDMEs showed more sustained 5-HT responses to increasing or changing FSCV waveform-switching potential and frequency, as well as to higher analyte concentrations. Biofouling-induced current reductions were significantly less pronounced at the BDDME when using a “Jackson” waveform compared to CFMEs. These findings are important steps towards the development and optimization of the BDDME as a chronically implanted biosensor for in vivo neurotransmitter detection. Full article

(This article belongs to the Special Issue Biosensors and Neuroscience)

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20 pages, 5096 KiB

Open AccessArticle

In Search of a Feedback Signal for Closed-Loop Deep Brain Stimulation: Stimulation of the Subthalamic Nucleus Reveals Altered Glutamate Dynamics in the Globus Pallidus in Anesthetized, 6-Hydroxydopamine-Treated Rats

by Mykyta M. Chernov, Christina B. Swan and James C. Leiter

Biosensors 2023, 13(4), 480; https://doi.org/10.3390/bios13040480 - 16 Apr 2023

Cited by 2 | Viewed by 1766

Abstract

Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a surgical procedure for alleviating motor symptoms of Parkinson’s Disease (PD). The pattern of DBS (e.g., the electrode pairs used and the intensity of stimulation) is usually optimized by trial and error based on a subjective evaluation of motor function. We tested the hypotheses that DBS releases glutamate in selected basal ganglia nuclei and that the creation of 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions alters glutamate release during DBS in those basal ganglia nuclei. We studied the relationship between a pseudo-random binary sequence of DBS and glutamate levels in the STN itself or in the globus pallidus (GP) in anesthetized, control, and 6-OHDA-treated rats. We characterized the stimulus–response relationships between DBS and glutamate levels using a transfer function estimated using System Identification. Stimulation of the STN elevated glutamate levels in the GP and in the STN. Although the 6-OHDA treatment did not affect glutamate dynamics in the STN during DBS in the STN, the transfer function between DBS in the STN and glutamate levels in the GP was significantly altered by the presence or absence of 6-OHDA-induced lesions. Thus, glutamate responses in the GP in the 6-OHDA-treated animals (but not in the STN) depended on dopaminergic inputs. For this reason, measuring glutamate levels in the GP may provide a useful feedback target in a closed-loop DBS device in patients with PD since the dynamics of glutamate release in the GP during DBS seem to reflect the loss of dopaminergic neurons in the SNc. Full article

(This article belongs to the Special Issue Biosensors and Neuroscience)

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22 pages, 6030 KiB

Open AccessArticle

Selective In Vitro and Ex Vivo Staining of Brain Neurofibrillary Tangles and Amyloid Plaques by Novel Ethylene Ethynylene-Based Optical Sensors

by Florencia A. Monge, Adeline M. Fanni, Patrick L. Donabedian, Jonathan Hulse, Nicole M. Maphis, Shanya Jiang, Tia N. Donaldson, Benjamin J. Clark, David G. Whitten, Kiran Bhaskar and Eva Y. Chi

Biosensors 2023, 13(2), 151; https://doi.org/10.3390/bios13020151 - 18 Jan 2023

Cited by 1 | Viewed by 2809

Abstract

The identification of protein aggregates as biomarkers for neurodegeneration is an area of interest for disease diagnosis and treatment development. In this work, we present novel super luminescent conjugated polyelectrolyte molecules as ex vivo sensors for tau-paired helical filaments (PHFs) and amyloid-β (Aβ) plaques. We evaluated the use of two oligo-p-phenylene ethynylenes (OPEs), anionic OPE₁²⁻ and cationic OPE₂⁴⁺, as stains for fibrillar protein pathology in brain sections of transgenic mouse (rTg4510) and rat (TgF344-AD) models of Alzheimer’s disease (AD) tauopathy, and post-mortem brain sections from human frontotemporal dementia (FTD). OPE₁²⁻ displayed selectivity for PHFs in fluorimetry assays and strong staining of neurofibrillary tangles (NFTs) in mouse and human brain tissue sections, while OPE₂⁴⁺ stained both NFTs and Aβ plaques. Both OPEs stained the brain sections with limited background or non-specific staining. This novel family of sensors outperformed the gold-standard dye Thioflavin T in sensing capacities and co-stained with conventional phosphorylated tau (AT180) and Aβ (4G8) antibodies. As the OPEs readily bind protein amyloids in vitro and ex vivo, they are selective and rapid tools for identifying proteopathic inclusions relevant to AD. Such OPEs can be useful in understanding pathogenesis and in creating in vivo diagnostically relevant detection tools for neurodegenerative diseases. Full article

(This article belongs to the Special Issue Biosensors and Neuroscience)

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11 pages, 1716 KiB

Open AccessArticle

Non-Invasive Electroretinogram Recording with Simultaneous Optogenetics to Dissect Retinal Ganglion Cells Electrophysiological Dynamics

by Eunji Hong, Christopher Glynn, Qianbin Wang and Siyuan Rao

Biosensors 2023, 13(1), 42; https://doi.org/10.3390/bios13010042 - 28 Dec 2022

Viewed by 3807

Abstract

Electroretinography (ERG) is a non-invasive electrophysiological recording technique that detects the electrical signaling of neuronal cells in the visual system. In conventional ERG recordings, the signals are considered a collective electrical response from various neuronal cell populations, including rods, cones, bipolar cells, and retinal ganglion cells (RGCs). However, due to the limited ability to control electrophysiological responses from different types of cells, the detailed information underlying ERG signals has not been analyzed and interpreted. Linking the features of ERG signals to the specific neuronal response will advance the understanding of neuronal electrophysiological dynamics and provide more evidence to elucidate pathological mechanisms, such as RGC loss during the progression of glaucoma. Herein, we developed an advanced ERG recording system integrated with a programmable, non-invasive optogenetic stimulation method in mice. In this system, we applied an automatic and unbiased ERG data analysis approach to differentiate a, b wave, negative response, and oscillatory potentials. To differentiate the electrophysiological response of RGCs in ERG recordings, we sensitized mouse RGCs with red-light opsin, ChRmine, through adeno-associated virus (AAV) intravitreal injection. Features of RGC dynamics under red-light stimulation were identified in the ERG readout. This non-invasive ERG recording system, associated with the programmable optogenetics stimulation method, provides a new methodology to dissect neural dynamics under variable physiological and pathological conditions in vivo. With the merits of non-invasiveness, improved sensitivity, and specificity, we envision this system can be further applied for early-stage detection of RGC degeneration and functional progression in neural degenerative diseases, such as glaucoma. Full article

(This article belongs to the Special Issue Biosensors and Neuroscience)

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18 pages, 3452 KiB

Open AccessArticle

A Fiber-Optic Sensor-Embedded and Machine Learning Assisted Smart Helmet for Multi-Variable Blunt Force Impact Sensing in Real Time

by Yiyang Zhuang, Taihao Han, Qingbo Yang, Ryan O’Malley, Aditya Kumar, Rex E. Gerald II and Jie Huang

Biosensors 2022, 12(12), 1159; https://doi.org/10.3390/bios12121159 - 13 Dec 2022

Cited by 2 | Viewed by 2468

Abstract

Early on-site diagnosis of mild traumatic brain injury (mTBI) will provide the best guidance for clinical practice. However, existing methods and sensors cannot provide sufficiently detailed physical information related to the blunt force impact. In the present work, a smart helmet with a single embedded fiber Bragg grating (FBG) sensor is developed, which can monitor complex blunt force impact events in real time under both wired and wireless modes. The transient oscillatory signal “fingerprint” can specifically reflect the impact-caused physical deformation of the local helmet structure. By combination with machine learning algorithms, the unknown transient impact can be recognized quickly and accurately in terms of impact magnitude, direction, and latitude. Optimization of the training dataset was also validated, and the boosted ML models, such as the S-SVM+ and S-IBK+, are able to predict accurately with complex databases. Thus, the ML-FBG smart helmet system developed by this work may become a crucial intervention alternative during a traumatic brain injury event. Full article

(This article belongs to the Special Issue Biosensors and Neuroscience)

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Review

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31 pages, 9800 KiB

Open AccessReview

Biosensors: Electrochemical Devices—General Concepts and Performance

by Oleh Smutok and Evgeny Katz

Biosensors 2023, 13(1), 44; https://doi.org/10.3390/bios13010044 - 28 Dec 2022

Cited by 21 | Viewed by 12331

Abstract

This review provides a general overview of different biosensors, mostly concentrating on electrochemical analytical devices, while briefly explaining general approaches to various kinds of biosensors, their construction and performance. A discussion on how all required components of biosensors are brought together to perform analytical work is offered. Different signal-transducing mechanisms are discussed, particularly addressing the immobilization of biomolecular components in the vicinity of a transducer interface and their functional integration with electronic devices. The review is mostly addressing general concepts of the biosensing processes rather than specific modern achievements in the area. Full article

(This article belongs to the Special Issue Biosensors and Neuroscience)

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