Transient electronic devices that dissolve after use without causing inflammatory reactions could open avenues to alternative medical applications. This article describes the development of an innovative device designed for two-month electrophysiological monitoring followed by biodegradation. The bioresorbable electrode array is composed of poly(lactic-co-glycolic acid) (PLGA), molybdenum (Mo), and an innovative poly(3,4-ethylenedioxythiophene) (PEDOT):hyaluronan (HA) conducting polymer. First, we characterized in vitro the device's biocompatibility and lifetime, monitoring the mass loss and the evolution of the electrode's electrochemical properties. Second, the devices were implanted cortically in rats and used to record electrochemical impedance and visual evoked potentials over a period of 205 days. In vitro and in vivo characterizations demonstrated the benefits of using bioresorbable conductive polymer ink for medium-term monitoring of biological signals since the device with ink coating showed a decrease in impedance compared to the electrode without ink coating. The lifetime of the conductive polymer was estimated at 28 days and 45 days, respectively, in vitro and in vivo. According to post-mortem neuroinflammation assessment in cortical tissues, we can claim that the devices remained biocompatible for their implantation lifetime. No measurable traces of Mo were found in either the brain or the liver, even using advanced characterization methods. We can assume that the conductive polymer safely degraded in vivo in less than two months. Such devices could be used in the future either for neural recording to guide the resection of epileptic foci or for electrical stimulation to improve wound healing mechanisms.
Electrochemical sensors integrated into organ-on-a-chip (OoC) - single-organ systems and more complex multi-organ (body-on-a-chip) - microfluidic platforms constitute a rapidly advancing interface between biosensing, microfluidics, and microphysiological systems (MPS), with major implications for biomedical research, drug discovery, toxicology, and personalized medicine. By transducing biochemical and biophysical events at the tissue-device interface into quantifiable electrical signals, these sensors enable real-time, label-free, and highly sensitive monitoring of metabolites, ions, barrier integrity, and cellular activity under physiologically relevant conditions. Within OoC and MPS platforms, electrochemical sensing can be implemented through different integration strategies, including on-chip configurations such as in-line and on-line sensing directly embedded within microfluidic channels, as well as off-chip approaches. The integration of miniaturized and multiplexed electrochemical sensors into MPS enables continuous and high-throughput functional monitoring of key physiological parameters, including metabolic activity variation, biomolecules gradients, barrier function, and responses to drugs and toxic compounds. Multi-OoC configurations benefit from electrochemical readouts to interrogate dynamic inter-organ communication and systemic responses, supporting more predictive human-relevant models. This is mostly relevant for new approach methodologies (NAMs), which aim to reduce animal experimentation while improving human relevance and predictive accuracy. Overall, electrochemical sensor-integrated OoC/MPS platforms represent powerful NAMs aligned with 3Rs (replacement, reduction, and refinement) principles, enabling high-throughput screening, improved physiological relevance, and enhanced predictive modeling for drug development and regulatory applications. In this review, we address recent advances in electrochemical sensor integration within OoC and MPS platforms, discussing fabrication strategies, sensing modalities, and system-level architectures, as well as current challenges and future perspectives.
Silicon is a valuable substrate for the design of biosensors and for micro/nanofluidic device fabrication, yet it remains challenging to achieve localized, tunable and robust surface functionalization. Existing methods such as hydrosylilation, silanization and electrografting often require multistep processing and harsh reagents like hydrofluoric acid. In this work, we introduce a one-step, aqueous electropolymerization strategy for directly functionalizing native oxide-bearing silicon with ultrathin polypyrrole (PPy) films. This is made possible by a simple dual pretreatment (plasma and oven) that enables stable, adherent PPy film formation using silicon as the working electrode. This film could be furtherly overoxidized to tune its conductivity and electroactivity. Homogeneous films with thicknesses ranging from 9 to similar to 70 nm were obtained and characterized by AFM, SEM, ellipsometry, XPS, Raman spectroscopy, and FTIR/ATR. Furthermore, the films were biofunctionalized with oligonucleotides or antibodies via co-electropolymerization with pyrrole conjugates. Fluorescence-based assays confirmed both the specificity and stability of biomolecule grafting. This approach offers scalable and biocompatible strategy for the fabrication of silicon-based biosensors and nanofluidic platforms requiring precise control of film morphology, surface charge, electrical properties, and functional groups.
Amorphous carbon, including diamond-like carbon (DLC) and carbon nitride (CNx), has emerged as a highly promising electrode material for electrochemical sensor development, owing to its exceptional physicochemical and electrochemical properties. These include a wide potential window, minimal background currents, high tolerance to extreme potentials, and enhanced resistance to fouling compared to conventional carbon-based electrodes. A major advantage of these materials is their cost-efficient production methods and the flexibility to synthesize them on a variety of substrates, including metals and polymers. This review aims to provide a comprehensive and up-to-date overview of electrochemical sensors based on amorphous carbon, serving as both a reference and a resource for researchers interested in leveraging these materials. It highlights the unique positioning of amorphous carbon compared to conventional electrode materials, emphasizing its advantages and potential applications. The discussion encompasses the physicochemical, electrochemical, and structural properties of amorphous carbon, with a focus on the influence of various deposition processes. Additionally, the review delves into advanced strategies such as doping and surface treatments that further enhance the performance of amorphous carbon coatings. Lastly, it presents a detailed compilation of electrochemical sensors utilizing amorphous carbon as the electrode material, showcasing their capabilities and the breadth of their applications in sensor technology.
This study investigates the synthesis and characterization of diamond-like carbon (DLC) films deposited via magnetron sputtering, aiming to optimize their properties for electrochemical electrode applications. Critical deposition parameters, such as temperature, negative bias, and nitrogen incorporation, were systematically adjusted to evaluate their impact on the film's structure and performance. Comprehensive characterization was performed using X-ray photoelectron spectroscopy, Raman spectroscopy, and scanning electron microscopy, alongside electrochemical techniques such as cyclic voltammetry and electrochemical impedance spectroscopy, to correlate physicochemical properties with electrochemical behavior. DLC films feature a smooth, dense surface with a wider potential window than boron doped diamond and other common electrode materials but generally lower conductivity and electrochemical reactivity. To overcome these limitations, a novel dual electrochemical activation treatment was developed, which significantly enhances electron transfer kinetics by a factor of six and doubles the redox peak currents compared to their initial values. This treatment also improves electrode uniformity and stability, highlighting the strong potential of optimized and activated DLC films for high-performance electrochemical applications.
Implantable and wearable bioelectronic systems are arising growing interest in the medical field. Linking the microelectronic (electronic conductivity) and biological (ionic conductivity) worlds, the biocompatible conductive materials at the electrode/tissue interface are key components in these systems. We herein focus more particularly on resorbable bioelectronic systems, which can safely degrade in the biological environment once they have completed their purpose, namely, stimulating or sensing biological activity in the tissues. Resorbable conductive materials are also explored in the fields of tissue engineering and 3D cell culture. After a short description of polymer-based substrates and scaffolds, and resorbable electrical conductors, we review how they can be combined to design resorbable conductive materials. Although these materials are still emerging, various medical and biomedical applications are already taking shape that can profoundly modify post-operative and wound healing follow-up. Future challenges and perspectives in the field are proposed.
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Conformable biocompatible conductive materials are increasingly sought for the development of bioelectronics. If additionally resorbable, they could serve for the design of transient implantable electronic devices, opening the way to new healthcare applications. Hyaluronan (HA) derivatives including sulfate and aminophenylboronic acid (PBA) groups (HAS-PBA) were therefore designed to serve as dopants of poly(3,4-ethylenedioxy)thiophene (PEDOT). The optimized HA sulfation protocol allowed good control on polymer sulfation degree while minimizing polymer chain degradation. Sulfated HA was shown to be degradable in physiological conditions. A synergy was observed between the sulfate negative charges and the PBA aromatic groups promoting hydrophobic interactions and π-stacking between PEDOT and HAS-PBA, to boost the material conductivity that reached 1.6 ± 0.2 S/cm in physiological conditions. Moreover the PEDOT:HAS-PBA material was not cytotoxic and could be formulated for easy processing by inkjet printing, appearing as promising candidate for the design of soft transient electronics for in vivo applications.
Fast bacterial detection and identification is a crucial challenge in order to improve our antibiotics use and reduce the antimicrobial resistance. Electroanalysis of biological fluids is cheap and can be done in situ but the electrode material needs to be perfectly chosen. We previously studied electrochemical signature of Pseudomonas aeruginosa's secretome, thanks to glassy carbon electrode. Some conductive polymers are particularly efficient for biological use because of their antifouling properties, biocompatibility and way of processing. In this paper, we described the fabrication, characterization and utilisation of PEDOT:PSS film to detect and identify Pseudomonas aeruginosa through three of its secreted molecules: pyocyanin, Pseudomonas quinolone PQS and 2 & PRIME;-aminoacetophenone. The electrochemical responses, clearly amplified by PEDOT:PSS, can be used to identify these bacteria quickly and efficiently.
According to the latest statistics, more than 537 million people around the world struggle with diabetes and its adverse consequences. As well as acute risks of hypo- or hyper- glycemia, long-term vascular complications may occur, including coronary heart disease or stroke, as well as diabetic nephropathy leading to end-stage disease, neuropathy or retinopathy. Therefore, there is an urgent need to improve diabetes management to reduce the risk of complications but also to improve patient's quality life. The impact of continuous glucose monitoring (CGM) is well recognized, in this regard. The current review aims at introducing the basic principles of glucose sensing, including electrochemical and optical detection, summarizing CGM technology, its requirements, advantages, and disadvantages. The role of CGM systems in the clinical diagnostics/ personal testing, difficulties in their utilization, and recommendations are also discussed. In the end, challenges and prospects in future CGM systems are discussed and non-invasive, wearable glucose biosensors are introduced. Though the scope of this review is CGMs and provides information about medical issues and analytical principles, consideration of broader use will be critical in future if the right systems are to be selected for effective diabetes management.
Bloodstream infections are a growing public health concern. Current pathogen identification systems are based on complex and expensive devices, intended for use in centralized laboratories. Subsequent identification requires harmful chemical reagents, specialized personnel and time. Here we describe a new approach for rapid and decentralized diagnosis of positive blood cultures using electrochemical sensors. By implementing a multi-material potentiometric platform in a blood culture bottle, we have developed a portable system for pathogen identification of Gram and of genus. Bacterial growth in human blood generates a specific label-free multiplex electrochemical fingerprint according to the detected species. Analysis of these fingerprints using homemade machine learning algorithms allow for rapid identification of the pathogen after detection (14 species and 9 genus) (GRAM= 99 % accuracy 5.75 h after detection, GENUS= 85 % accuracy 7.8 h after positivity) without further handling of the contaminated sample.
A PEDOT:hyaluronic acid ink was printed on a PLGA film, then UV-crosslinked to design non soluble conductive patterns. The ink was fully resorbable within 2 months when immersed in water, paving the way towards transient bioelectronic devices.
Electrochemical impedance spectroscopy (EIS) is widely accepted as an effective and non-destructive method to assess cell health during cell-culture. However, there is a lack of compact devices compatible with microfluidic integration and microscopy that could provide the real-time and non-invasive monitoring of cell-cultures using EIS. In this paper, we reported the design and characterization of a modular EIS testing system based on a patented technology. This device was fabricated using easily processable methodologies including screen-printing of the impedance electrodes and molding or micromachining of the cell culture chamber with an easy assembly procedure. Accordingly, to obtain processable, biocompatible and sterilizable electrode materials that lower the impact of interfacial impedance on TEER (Transepithelial electrical resistance) measurements, and to enable concomitant microscopy observations, we optimized the formulation of the electrode inks and the design of the EIS electrodes, respectively. First, electrode materials were based on carbon biocompatible inks enriched with IrOx particles to obtain low interfacial impedance electrodes approaching the performances of classical non-biocompatible Ag/AgCl second-species electrodes. Secondly, we proposed three original electrode designs, which were compared to classical disk electrodes that were optically compatible with microscopy. We assessed the impact of the electrode design on the response of the impedance sensor using COMSOL Multiphysics. Finally, the performance of the impedance spectroscopy devices was assessed in vitro using human airway epithelial cell cultures.
Despite decades of research on the reduction of surface fouling from biomolecules or micro-organisms, the ultimate antibiofouling surface remains undiscovered. The recent covid-19 pandemic strengthened the crucial need for such treatments. Among the numerous approaches that are able to provide surfaces with antibiofouling properties, chemical, biological, and topographical strategies have been implemented for instance in the marine, medical, or food industries. However, many of these methods have a biocidal effect and, with antibioresistance and biocide resistance a growing threat on humanity, strategies based on reducing adsorption of biomolecules and micro-organism are necessary for long-term solutions. Bioinspired strategies, combining both surface chemistry and topography, are currently at the heart of the best innovative and sustainable solutions. The synergistic effect of micro/nanostructuration, together with engineered chemical or biological functionalization is believed to contribute to the development of antibiofouling surfaces. This review aims to present approaches combining hydrophobic or hydrophilic chemistries with a specific topography to avoid biofouling in various industrial environments and healthcare facilities.
We present a preliminary study of a wearable system to monitor biomarkers for dairy and suckling cattle. Finding the optimal location on the cow body (ears) and designing the adapted microneedles to reach the interstitial fluids underneath the cow skin are the two points addressed here.For the selection of the location, 4 breeds of suckling cows (Aubrac, Charolaise, Lim-ousine, Salers) and 3 breeds of dairy cows (Abondance, Montbe ?liarde, Holstein) were chosen. Measurements of the thickness of the ear tissues were conducted on three areas of the ear (top, apex and base of the pinna), on the external and internal sides. Results show that the apex of the pinna, external side, is the best area for microneedle implantation with an implantation window of 1403 +/- 589 mm (DeepDe), considering all breeds. To reach this implantation window located between the stratum corneum and the cartilage, the microneedle has to pass through 1323 +/- 404 mm of tissues (SupDe), considering all breeds. From these results, a microneedle design was made on SolidWorks. With a conical shape 2.89 mm in height and a conical channel 300 mm in diameter (at the tip of the microneedle), the model was made using 3D printing. The resulting microneedles respect the SolidWorks design with fair accuracy. They were connected to a microfluidic channel for sampling or releasing fluids.(c) 2022 IAgrE. Published by Elsevier Ltd. All rights reserved.
Biocompatibility testing is usually performed through staining and imaging of cell lines. We propose here to monitor cytotoxicity through real-time measurement of metabolites specifically issued from cell stress behaviour using a multiparametric electrochemical (bio)sensing platform. However, the composition of culture media varies widely according to the requirements of the utilized cell lines. This matter may have significant effects on the sensor's sensitivity. With this mind, the sensitivity of four electrochemical (bio)sensors (pH, hydrogen peroxide, nitric oxide/nitrite (NO and its by-product) and lactate) is investigated in different cell culture media. The main culture media studied were Minimum Essential Medium Eagle (MEM), Dulbecco's Modified Eagle Medium (DMEM), Williams ' Medium E and RPMI 1640 medium that were the recommended culture media for the cell types to be monitored. This work shows the impact of the different cell culture media on the performances of the different sensors (limit of detection, sensitivity, selectivity, response time and dynamic range). More particularly, FBS strongly impacts the response of the amperometric (bio)sensors. Then, cellular viability testing was effected within optimized medium (FBS content) for electrochemical sensor read-outs in the case of short-term cultures (one day) devoted to cytotoxicity testing. Real-time electrochemical monitoring provides important additional information about cell behaviour during biocompatibility testing that might be further implemented in different settings including pharmaceutical efficacy and biomaterials applications.
There is a growing need for real-time monitoring of metabolic products that could reflect cell damages over extended periods. In this paper, we report the design and development of an original multiparametric (bio)sensing platform that is tailored for the real-time monitoring of cell metabolites derived from cell cultures. Most attractive features of our developed electrochemical (bio)sensing platform are its easy manufacturing process, that enables seamless scale-up, modular and versatile approach, and low cost. In addition, the developed platform allows a multiparametric analysis instead of single-analyte analysis. Here we provide an overview of the sensors-based analysis of four main factors that can indicate a possible cell deterioration problem during cell-culture: pH, hydrogen peroxide, nitric oxide/nitrite and lactate. Herein, we are proposing a sensors platform based on thick-film coupled to microfluidic technology that can be integrated into any microfluidic system using Luer-lock connectors. This platform allows obtaining an accurate analysis of the secreting stress metabolites during cell/tissues culture.
During infections, fast identification of the microorganisms is critical to improve patient treatment and to better manage antibiotics use. Electrochemistry exhibits several advantages for rapid diagnostic: it enables easy, cheap and in situ analysis of redox molecules in most liquids. In this work, several culture supernatants of different Pseudomonas aeruginosa strains (including PAO1 and its isogenic mutants PAO1ΔpqsA, PA14, PAK and CHA) were analyzed by square wave voltammetry on glassy carbon electrode during the bacterial growth. The obtained voltamograms shown complex traces exhibiting numerous redox peaks with potential repartitions and current amplitudes depending on the studied bacterium and/or growth time. Among them, some peaks were clearly associated to the well-known redox toxin Pyocyanin (PYO) and the autoinducer Pseudomonas Quinolone Signal (PQS). Other peaks were observed that are not yet attributed to known secreted species. Each complex electrochemical response (number of peaks, peak potential and amplitude) can be interpreted as a fingerprint or "ID-card" of the studied strain that may be implemented for fast bacteria strain identification.
Nitric oxide (NO) and its by-products are important biological signals in human physiology and pathology particularly in the vascular and immune systems. Thus, in situ determination of the NO-related molecule (NOx) levels using embedded sensors is of high importance particularly in the context of cellular biocompatibility testing. However, NOx analytical reference method dedicated to the evaluation of biomaterial biocompatibility testing is lacking. Herein, we demonstrate a PAPA-NONOate-based reference method for the calibration of NOx sensors. After, the validation of this reference method and its potentialities were demonstrated for the detection of the oxidative stress-related NO secretion of vascular endothelial cells in a 3D tissue issued from 3D printing. Such NOx detection method can be an integral part of cell response to biomaterials.
The localized functionalization of pores and channels of micrometric and sub‐micrometric sizes is a bottleneck in surface chemistry. A method for the regioselective chemical functionalization of planar pores is presented, that are, restrictions in microfluidic channels, here made of SiO 2 ‐coated silicon. This strategy, based on bipolar electrochemistry, exploits the combined presence of the constriction and a localized deoxidation pattern within the pore that affects the electrical field distribution inside the microfluidic channel. It is not only shown that it is capable of regioselectively functionalizing a planar pore at relatively small potential difference applied across it, but also the possibility of positioning the functionalization area inside or at the edges of the pore depending on the design of the deoxidation pattern is proved. These results are in perfect correlation with the numerical simulations of electric field distribution in micropores carried out using the software Comsol Multiphysics. This functionalization technique is therefore very promising, particularly in the field of biosensors. A specific DNA hybridization test has been successfully carried out, which represents a first step toward bioanalytical and health applications.