Simultaneous Dopamine and Serotonin Monitoring in Freely Moving Crayfish Using a Wireless Electrochemical Sensing System.

Dopamine (DA) and serotonin (5-HT) are neurotransmitters that regulate a wide range of physiological and behavioral processes. Monitoring of both neurotransmitters with real-time analysis offers important insight into the mechanisms that shape animal behavior. However, bioelectronic tools to simultaneously monitor DA and 5-HT interactive dynamics in freely moving animals are underdeveloped. This is mainly due to the limited sensor sensitivity with miniaturized electronics. Here, we present a semi-implantable electrochemical device achieved by integrating a multi-surface-modified carbon fiber microelectrode with a miniaturized potentiostat module to detect DA and 5-HT in vivo with high sensitivity and selectivity. Specifically, carbon fiber microelectrodes were modified through electrochemical treatment and surface coatings to improve sensitivity, selectivity, and antifouling properties. A customized, lightweight potentiostat module was developed for untethered electrochemical measurements. Integrated with the microelectrode, the microsystem is compact (2.8 × 2.3 × 2.1 cm) to minimize its impacts on animal behavior and achieved simultaneous detection of DA and 5-HT with sensitivities of 48.4 and 133.0 nA/µM, respectively, within submicromolar ranges. The system was attached to the crayfish dorsal carapace, allowing electrode implantation into the heart of a crayfish to monitor DA and 5-HT dynamics, followed by drug injections. The semi-implantable biosensor system displayed a significant increase in oxidation peak currents after DA and 5-HT injections. The device successfully demonstrated the application for in vivo simultaneous monitoring of DA and 5-HT in the hemolymph (i.e., blood) of freely behaving crayfish underwater, yielding a valuable experimental tool to expand our understanding of the comodulation of DA and 5-HT.

Miniaturized Capsule System Toward Real-Time Electrochemical Detection of H2 S in the Gastrointestinal Tract.

Hydrogen sulfide (H2 S) is a gaseous inflammatory mediator and important signaling molecule for maintaining gastrointestinal (GI) homeostasis. Excess intraluminal H2 S in the GI tract has been implicated in inflammatory bowel disease and neurodegenerative disorders; however, the role of H2 S in disease pathogenesis and progression is unclear. Herein, an electrochemical gas-sensing ingestible capsule is developed to enable real-time, wireless amperometric measurement of H2 S in GI conditions. A gold (Au) three-electrode sensor is modified with a Nafion solid-polymer electrolyte (Nafion-Au) to enhance selectivity toward H2 S in humid environments. The Nafion-Au sensor-integrated capsule shows a linear current response in H2 S concentration ranging from 0.21 to 4.5 ppm (R2 = 0.954) with a normalized sensitivity of 12.4% ppm-1 when evaluated in a benchtop setting. The sensor proves highly selective toward H2 S in the presence of known interferent gases, such as hydrogen (H2 ), with a selectivity ratio of H2 S:H2 = 1340, as well as toward methane (CH4 ) and carbon dioxide (CO2 ). The packaged capsule demonstrates reliable wireless communication through abdominal tissue analogues, comparable to GI dielectric properties. Also, an assessment of sensor drift and threshold-based notification is investigated, showing potential for in vivo application. Thus, the developed H2 S capsule platform provides an analytical tool to uncover the complex biology-modulating effects of intraluminal H2 S.

Freestanding region-responsive bilayer for functional packaging of ingestible devices.

Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal (GI) disease. As device complexity increases, so too does the demand for more effective capsule packaging technologies to elegantly target specific GI locations. While pH-responsive coatings have been traditionally used for the passive targeting of specific GI regions, their application is limited due to the geometric restrictions imposed by standard coating methods. Dip, pan, and spray coating methods only enable the protection of microscale unsupported openings against the harsh GI environment. However, some emerging technologies have millimeter-scale components for performing functions such as sensing and drug delivery. To this end, we present the freestanding region-responsive bilayer (FRRB), a packaging technology for ingestible capsules that can be readily applied for various functional ingestible capsule components. The bilayer is composed of rigid polyethylene glycol (PEG) under a flexible pH-responsive Eudragit® FL 30 D 55, which protects the contents of the capsule until it arrives in the targeted intestinal environment. The FRRB can be fabricated in a multitude of shapes that facilitate various functional packaging mechanisms, some of which are demonstrated here. In this paper, we characterize and validate the use of this technology in a simulated intestinal environment, confirming that the FRRB can be tuned for small intestinal release. We also show a case example where the FRRB is used to protect and expose a thermomechanical actuator for targeted drug delivery.

A portable electrochemical sensing platform for serotonin detection based on surface-modified carbon fiber microelectrodes.

Serotonin (5-HT) is one of the key neurotransmitters in the human body, regulating numerous physiological functions. A disruption in 5-HT homeostasis could result in serious health problems, including neurodegenerative disorders, depression, and 5-HT syndrome. Detection of 5-HT concentrations in biological fluids, such as urine, is a potential solution for early diagnosis of these diseases. In this study, we developed a novel, simple, and low-cost electrochemical sensing platform consisting of a portable workstation with customized electrodes for 5-HT detection in artificial biological fluids. Nafion/carbon nanotubes (CNTs) and electrochemically modified carbon fiber microelectrodes (Nafion-CNT/EC CFMEs) displayed improved 5-HT sensitivity and selectivity. Together with a customized Ag/AgCl reference electrode and Pt counter electrode, the portable 5-HT sensing platform had a sensitivity of 0.074 µA µM-1 and a limit of detection (LOD) of 140 nM. This system was also assessed to measure 5-HT spiked in artificial urine samples, showing nearly full recovery rates. These satisfactory results demonstrated that the portable system exhibits outstanding performance and confirmed the feasibility of 5-HT detection, which can be used to provide point-of-care analysis in actual biological samples.

Adsorption Kinetic Model Predicts and Improves Reliability of Electrochemical Serotonin Detection.

Serotonin (5-HT) is a neurotransmitter involved in many biophysiological processes in the brain and in the gastrointestinal tract. Electrochemical methods are commonly used to quantify 5-HT, but their reliability may suffer due to the time-dependent nature of adsorption-limited 5-HT detection, as well as electrode fouling over repeated measurements. Mathematical characterization and modeling of adsorption-based electrochemical signal generation would improve reliability of 5-HT measurement. Here, a model was developed to track 5-HT electrode adsorption and resulting current output by combining Langmuir adsorption kinetic equations and adsorption-limited electrochemical equations. 5-HT adsorption binding parameters were experimentally determined at a carbon-nanotube coated Au electrode: KD = 7 × 10-7 M, kon = 130 M-1 s-1, koff = 9.1 × 10-5 s-1. A computational model of 5-HT adsorption was then constructed, which could effectively predict 5-HT fouling over 50 measurements (R2 = 0.9947), as well as predict electrode responses over varying concentrations and measurement times. The model aided in optimizing the measurement of 5-HT secreted from a model enterochromaffin cell line-RIN14B-minimizing measurement time. The presented model simplified and improved the characterization of 5-HT detection at the selected electrode. This could be applied to many other adsorption-limited electrochemical analytes and electrode types, contributing to the improvement of application-specific modeling and optimization processes.

Reprogramming Virus Coat Protein Carboxylate Interactions for the Patterned Assembly of Hierarchical Nanorods.

The self-assembly system of the rod-shaped tobacco mosaic virus (TMV) has been studied extensively for nanoscale applications. TMV coat protein assembly is modulated by intersubunit carboxylate groups whose electrostatic repulsion limits the assembly of virus rods without incorporating genomic RNA. To engineer assembly control into this system, we reprogrammed intersubunit carboxylate interactions to produce self-assembling coat proteins in the absence of RNA and in response to unique pH and ionic environmental conditions. Specifically, engineering a charge attraction at the intersubunit E50-D77 carboxylate group through a D77K substitution stabilized the coat proteins assembly into virus-like rods. In contrast, the reciprocal E50K modification alone did not confer virus-like rod assembly. However, a combination of R46G/E50K/E97G substitutions enabled virus-like rod assembly. Interestingly, the D77K substitution displays a unique pH-dependent assembly-disassembly profile, while the R46G/E50K/E97G substitutions confer a novel salt concentration dependency for assembly control. In addition, these unique environmentally controlled coat proteins allow for the directed assembly and disassembly of chimeric virus-like rods both in solution and on substrate-attached seed rods. Combined, these findings provide a controllable means to assemble functionally discrete virus-like rods for use in nanotechnology applications.

Integrated System for Bacterial Detection and Biofilm Treatment on Indwelling Urinary Catheters.

GOAL: This work introduces an integrated system incorporated seamlessly with a commercial Foley urinary catheter for bacterial growth sensing and biofilm treatment. METHODS: The system is comprised of flexible, interdigitated electrodes incorporated with a urinary catheter via a 3D-printed insert for impedance sensing and bioelectric effect-based treatment. Each of the functions were wirelessly controlled using a custom application that provides a user-friendly interface for communicating with a custom PCB via Bluetooth to facilitate implementation in practice. RESULTS: The integrated catheter system maintains the primary functions of indwelling catheters - urine drainage, balloon inflation - while being capable of detecting the growth of Escherichia coli, with an average decrease in impedance of 13.0% after 24 hours, tested in a newly-developed simulated bladder environment. Furthermore, the system enables bioelectric effect-based biofilm reduction, which is performed by applying a low-intensity electric field that increases the susceptibility of biofilm bacteria to antimicrobials, ultimately reducing the required antibiotic dosage. CONCLUSION: Overall, this modified catheter system represents a significant step forward for catheter-associated urinary tract infection (CAUTI) management using device-based approaches, integrating flexible electrodes with an actual Foley catheter along with the control electronics and mobile application. SIGNIFICANCE: CAUTIs, exacerbated by the emergence of antibiotic-resistant pathogens, represent a significant challenge as one of the most prevalent healthcare-acquired infections. These infections are driven by the colonization of indwelling catheters by bacterial biofilms.

Draft Genome Sequence of Pseudomonas aeruginosa Strain PA14-UM.

Pseudomonas aeruginosa is a Gram-negative nosocomial pathogen that is a leading cause of morbidity and mortality in cystic fibrosis patients and immunocompromised individuals worldwide. The isolate examined in this study, PA14-UM, is a well-characterized isolate utilized in studies from the University of Maryland.

Capacitive sensing of triglyceride film reactions: a proof-of-concept demonstration for sensing in simulated duodenal contents with gastrointestinal targeting capsule system.

Ingestible capsule systems continue to evolve to overcome drawbacks associated with traditional gastrointestinal (GI) diagnostic and therapeutic processes, such as limitations on which sections of the GI tract can be accessed or the inability to measure local biomarker concentrations. We report an integrated capsule sensing system, utilizing a hybrid packaging scheme coupled with triglyceride film-coated capacitive sensors, for measuring biochemical species present in the duodenum, such as pancreatic lipase and bile acids. The system uses microfabricated capacitive sensors interfaced with a Bluetooth low-energy (BLE)-microcontroller, allowing wireless connectivity to a mobile app. The triglyceride films insulate the sensor surface and react either with 0.01-1 mM lipase via hydrolysis or 0.07-7% w/v bile acids via emulsification in simulated fluids, leading to measurable changes in capacitance. Cross reactivity of the triglyceride films is evaluated in both phosphate buffered saline (PBS) as well as pancreatic trypsin solutions. The film morphology is observed after exposure to each stimulus to better understand how these changes alter the sensor capacitance. The capsule utilizes a 3D-printed package coated with polymers that remain intact in acid solution (mimicking gastric conditions), then dissolve at a duodenum-mimicking neutral pH for triggered opening of the sensing chamber from which we can subsequently detect the presence of pancreatic lipase. This device strategy represents a significant step towards using embedded packaging and triglyceride-based materials to target specific regions of the GI tract and sensing biochemical contents for evaluating gastrointestinal health.

Ingestible Sensors and Sensing Systems for Minimally Invasive Diagnosis and Monitoring: The Next Frontier in Minimally Invasive Screening.

Ingestible electronic systems that are capable of embedded sensing, particularly within the gastrointestinal (GI) tract and its accessory organs, have the potential to screen for diseases that are difficult if not impossible to detect at an early stage using other means. Furthermore, these devices have the potential to (1) reduce labor and facility costs for a variety of procedures, (2) promote research for discovering new biomarker targets for associated pathologies, (3) promote the development of autonomous or semiautonomous diagnostic aids for consumers, and (4) provide a foundation for epithelially targeted therapeutic interventions. These technological advances have the potential to make disease surveillance and treatment far more effective for a variety of conditions, allowing patients to lead longer and more productive lives. This review will examine the conventional techniques, as well as ingestible sensors and sensing systems that are currently under development for use in disease screening and diagnosis for GI disorders. Design considerations, fabrication, and applications will be discussed.

Microsystems for biofilm characterization and sensing - A review.

Biofilms are the primary cause of clinical bacterial infections and are impervious to typical amounts of antibiotics, necessitating very high doses for elimination. Therefore, it is imperative to have suitable methods for characterization to develop novel methods of treatment that can complement or replace existing approaches using significantly lower doses of antibiotics. This review presents some of the current developments in microsystems for characterization and sensing of bacterial biofilms. Initially, we review current standards for studying biofilms that are based on invasive and destructive end-point biofilm characterization. Additionally, biofilm formation and growth is extremely sensitive to various growth and environmental parameters that cause large variability in biofilms between repeated experiments, making it very difficult to compare experimental repeats and characterize the temporal characteristics of these organisms. To address these challenges, recent developments in the field have moved toward systems and miniature devices that can aid in the non-invasive characterization of bacterial biofilms. Our review focuses on several types of microsystems for biofilm evaluation including optical, electrochemical, and mechanical systems. This review will show how these devices can lead to better understanding of the physiology and function of these communities of bacteria, which can eventually lead to the development of novel treatments that do not rely on high-dosage antibiotics.

Electrochemical measurement of serotonin by Au-CNT electrodes fabricated on microporous cell culture membranes.

Gut-brain axis (GBA) communication relies on serotonin (5-HT) signaling between the gut epithelium and the peripheral nervous system, where 5-HT release patterns from the basolateral (i.e., bottom) side of the epithelium activate nerve afferents. There have been few quantitative studies of this gut-neuron signaling due to a lack of real-time measurement tools that can access the basolateral gut epithelium. In vitro platforms allow quantitative studies of cultured gut tissue, but they mainly employ offline and endpoint assays that cannot resolve dynamic molecular-release patterns. Here, we present the modification of a microporous cell culture membrane with carbon nanotube-coated gold (Au-CNT) electrodes capable of continuous, label-free, and direct detection of 5-HT at physiological concentrations. Electrochemical characterization of single-walled carbon nanotube (SWCNT)-coated Au electrodes shows increased electroactive surface area, 5-HT specificity, sensitivity, and saturation time, which are correlated with the CNT film drop-cast volume. Two microliters of CNT films, with a 10-min saturation time, 0.6 µA/µM 5-HT sensitivity, and reliable detection within a linear range of 500 nM-10 µM 5-HT, can be targeted for high-concentration, high-time-resolution 5-HT monitoring. CNT films (12.5 µL) with a 2-h saturation time, 4.5 µA/µM 5-HT sensitivity, and quantitative detection in the linear range of 100 nM-1 µM can target low concentrations with low time resolution. These electrodes achieved continuous detection of dynamic diffusion across the porous membrane, mimicking basolateral 5-HT release from cells, and detection of cell-released 5-HT from separately cultured RIN14B cell supernatant. Electrode-integrated cell culture systems such as this can improve in vitro molecular detection mechanisms and aid in quantitative GBA signaling studies.

3D-Printed electrochemical sensor-integrated transwell systems.

This work presents a 3D-printed, modular, electrochemical sensor-integrated transwell system for monitoring cellular and molecular events in situ without sample extraction or microfluidics-assisted downstream omics. Simple additive manufacturing techniques such as 3D printing, shadow masking, and molding are used to fabricate this modular system, which is autoclavable, biocompatible, and designed to operate following standard operating protocols (SOPs) of cellular biology. Integral to the platform is a flexible porous membrane, which is used as a cell culture substrate similarly to a commercial transwell insert. Multimodal electrochemical sensors fabricated on the membrane allow direct access to cells and their products. A pair of gold electrodes on the top side of the membrane measures impedance over the course of cell attachment and growth, characterized by an exponential decrease (~160% at 10 Hz) due to an increase in the double layer capacitance from secreted extracellular matrix (ECM) proteins. Cyclic voltammetry (CV) sensor electrodes, fabricated on the bottom side of the membrane, enable sensing of molecular release at the site of cell culture without the need for downstream fluidics. Real-time detection of ferrocene dimethanol injection across the membrane showed a three order-of-magnitude higher signal at the membrane than in the bulk media after reaching equilibrium. This modular sensor-integrated transwell system allows unprecedented direct, real-time, and noninvasive access to physical and biochemical information, which cannot be obtained in a conventional transwell system.

Flexible Platform for In Situ Impedimetric Detection and Bioelectric Effect Treatment of Escherichia Coli Biofilms.

GOAL: This paper reports a platform for real-time monitoring and treatment of biofilm formation on three-dimensional biomedical device surfaces. METHODS: We utilize a flexible platform consisting of gold interdigitated electrodes patterned on a polyimide substrate. The device was integrated onto the interior of a urinary catheter and characterization was performed in a custom-developed flow system. Biofilm growth was monitored via impedance change at 100 Hz ac with a 50 mV signal amplitude. RESULTS: A 30% impedance decrease over 24 h corresponded to Escherichia coli biofilm formation. The platform also enabled removal of the biofilm through the bioelectric effect; a low concentration of antibiotic combined with the applied ac voltage signal led to a synergistic reduction in biofilm resulting in a 12% increase in impedance. Biomass characterization via crystal violet staining confirmed that the impedance detection results correlate with changes in the amount of biofilm biomass on the sensor. We also demonstrated integration with a chip-based impedance converter to enable miniaturization and allow in situ wireless implementation. A 5% impedance decrease measured with the impedance converter corresponded to biofilm growth, replicating the trend measured with the potentiostat. CONCLUSION: This platform represents a promising solution for biofilm infection management in diverse vulnerable environments. SIGNIFICANCE: Biofilms are the dominant mode of growth for microorganisms, where bacterial cells colonize hydrated surfaces and lead to recurring infections. Due to the inaccessible nature of the environments where biofilms grow and their increased tolerance of antimicrobials, identification, and removal on medical devices poses a challenge.

Tobacco Mosaic Virus as a Versatile Platform for Molecular Assembly and Device Fabrication.

Viruses are unique biological agents that infect living host cells through molecular delivery of a genomic cargo. Over the past two decades advancements in genetic engineering and bioconjugation technologies have allowed the unprecedented use of these "unfriendly" biological molecules, as nanoscopic platforms for the advancement of an array of nanotechnology applications. This mini-review focuses on providing a brief summary of key demonstrations leveraging the versatile characteristics of Tobacco mosaic virus (TMV) for molecular assembly and bio-device integration. A comprehensive discussion of genetic and chemical modification strategies along with potential limiting factors that impact the assembly of these macromolecules is presented to provide useful insights for adapting TMV as a potentially universal platform toward developing advanced nanomaterials. Additional discussions on biofabrication techniques developed in parallel to enable immobilization, alignment, and patterning of TMV-based functional particles on solid surfaces will highlight technological innovations that can be widely adapted for creating nanoscopic device components using these engineered biomacromolecules. Further exploitation in the design of molecular specificity and assembly mechanisms and the development of highly controllable and scalable TMV-device integration strategies will expand the library of nanoscale engineering tools that can be used for the further development of virus-based nanotechnology platforms.

Localized Three-Dimensional Functionalization of Bionanoreceptors on High-Density Micropillar Arrays via Electrowetting.

In this work, we introduce an electrowetting-assisted 3-D biofabrication process allowing both complete and localized functionalization of bionanoreceptors onto densely arranged 3-D microstructures. The integration of biomaterials with 3-D microdevice components offers exciting opportunities for communities developing miniature bioelectronics with enhanced performance and advanced modes of operation. However, most biological materials are stable only in properly conditioned aqueous solutions, thus the water-repellent properties exhibited by densely arranged micro/nanostructures (widely known as the Cassie-Baxter state) represent a significant challenge to biomaterial integration. Here, we first investigate such potential limitations using cysteine-modified tobacco mosaic virus (TMV1cys) as a model bionanoreceptor and a set of Au-coated Si-micropillar arrays (µPAs) of varying densities. Furthermore, we introduce a novel biofabrication system adopting electrowetting principles for the controlled localization of TMV1cys bionanoreptors on densely arranged µPAs. Contact angle analysis and SEM characterizations provide clear evidence to indicate structural hydrophobicity as a key limiting factor for 3-D biofunctionalization and for electrowetting as an effective method to overcome this limitation. The successful 3-D biofabrication is confirmed using SEM and fluorescence microscopy that show spatially controlled and uniform assemblies of TMV1cys on µPAs. The increased density of TMV1cys per device footprint produces a 7-fold increase in fluorescence intensity attributed to the µPAs when compared to similar assemblies on planar substrates. Combined, this work demonstrates the potential of electrowetting as a unique enabling solution for the controlled and efficient biofabrication of 3-D-patterned micro/nanodomains.

The Role of Microsystems Integration Towards Point-of-Care Clozapine Treatment Monitoring in Schizophrenia.

We present a perspective on microsystems integration aspects for concurrent cellular and molecular sensing in a lab-on-a-chip device. While of interest for a range of applications, very few - narrowly focused - examples of such devices can be found in the literature. Here, we approach the challenge from a systems level, considering sensor integration both in parallel and in series. Our study is specifically geared toward schizophrenia treatment, where concurrent blood monitoring of the antipsychotic clozapine and white blood cells could lead to improved treatment outcomes. We evaluate the critical system components for either design, namely plasma skimming (parallel) and in-blood clozapine detection (series). We find that plasma skimming is infeasible, but for the first time demonstrate direct detection of clozapine in whole blood. With a corresponding series-integrated microsystem, we finally demonstrate downstream white blood cell analysis on the same samples using impedance cytometry. We thus present the first lab-on-a-chip device capable of label- and reagent-free concurrent sensing of cellular and molecular markers.

Blood Draw Barriers for Treatment with Clozapine and Development of a Point-of-Care Monitoring Device.

BACKGROUND: While clozapine (CLZ) is the most effective antipsychotic drug for schizophrenia treatment, it remains underused. In order to understand the barriers of frequent blood draws for white blood cell counts (WBCs) and clozapine levels, we developed a psychiatrist survey and began an integrative approach of designing a point-of-care device that could eventually have real-time monitoring with immediate results. METHODS: We ascertained barriers related to CLZ management and the acceptance of possible solutions by sending an anonymous survey to physicians in psychiatric practice (n=860). In parallel, we tested CLZ sensing using a prototype point-of-care monitoring device. RESULTS: 255 responses were included in the survey results. The two barriers receiving mean scores with the highest agreement as being a significant barrier were patient nonadherence to blood work and blood work's burden on the patient (out of 28). Among nine solutions, the ability to obtain lab results in the physician's office or pharmacy was top ranked (mean±sd Likert scale [4.0±1.0]). Physicians responded that a point-of-care device to measure blood levels and WBCs would improve care and increase CLZ use. Residents ranked point-of-care devices higher than older physicians (4.07±0.87 vs. 3.47±1.08, p<0.0001). Also, the prototype device was able to detect CLZ reliably in 1.6, 8.2, and 16.3 µg/mL buffered solutions. DISCUSSION: Survey results demonstrate physicians' desire for point-of-care monitoring technology, particularly among younger prescribers. Prototype sensor results identify that CLZ can be detected and integrated for future device development. Future development will also include integration of WBCs for a complete detection device.

An Integrated Microsystem for Real-Time Detection and Threshold-Activated Treatment of Bacterial Biofilms.

Bacterial biofilms are the primary cause of infections in medical implants and catheters. Delayed detection of biofilm infections contributes to the widespread use of high doses of antibiotics, leading to the emergence of antibiotic-resistant bacterial strains. Accordingly, there is an urgent need for systems that can rapidly detect and treat biofilm infections in situ. As a step toward this goal, in this work we have developed for the first time a threshold-activated feedback-based impedance sensor-treatment system for combined real-time detection and treatment of biofilms. Specifically, we demonstrate the use of impedimetric sensing to accurately monitor the growth of Escherichia coli biofilms in microfluidic flow cells by measuring the fractional relative change (FRC) in absolute impedance. Furthermore, we demonstrate the use of growth measurements as a threshold-activated trigger mechanism to initiate successful treatment of biofilms using bioelectric effect (BE), applied through the same sensing electrode array. This was made possible through a custom program that (a) monitored the growth and removal of biofilms within the microfluidic channels in real-time and (b) enabled the threshold-based activation of BE treatment. Such BE treatment resulted in a ∼74.8 % reduction in average biofilm surface coverage as compared to the untreated negative control. We believe that this smart microsystem for integrated biofilm sensing and treatment will enable future development of autonomous biosensors optimized for accurate real-time detection of the onset of biofilms and their in situ treatment, directly on the surfaces of medical implants.