Eunkyoung Kim

• University of Maryland, College Park

Redox provides unique opportunities for interconverting molecular/biological information into electronic signals. Here, the fabrication of a 3D‐printed multiwell device that can be interfaced into existing laboratory instruments (e.g., well‐plate readers and microscopes) to enable advanced redox‐based spectral and electrochemical capabilities is re...

The proline amino acid and prolyl residues of peptides/proteins confer unique biological and biochemical properties that motivates the development of proline‐selective analysis. The study focuses on one specific class of problem, the detection of single amino acid variants involving proline, and reports a Pro‐selective electrochemiluminescence (ECL...

Protein function relies on sequence, folding and post-translational modification and molecular measurements are commonly used to reveal these structural features. Here, we report an alternative approach that represents these molecular features as readily measurable electronic patterns and validate this experimental approach by detecting structural...

We report the integration of 3D printing, electrobiofabrication, and protein engineering to create a device that enables near real‐time analysis of monoclonal antibody (mAb) titer and quality. 3D printing was used to create the macroscale architecture that can control fluidic contact of a sample with multiple electrodes for replicate measurements....

Melanin has been surprisingly difficult to characterize using either bottom-up studies focused on molecular structure or top-down studies focused on functional properties. We have been developing electrochemical methods to understand the redox-activities of melanin. These studies show that melanins from various sources: (i) are reversibly redox-act...

Microelectronic devices can directly communicate with biology, as electronic information can be transmitted via redox reactions within biological systems. By engineering biology’s native redox networks, we enable electronic interrogation and control of biological systems at several hierarchical levels: proteins, cells, and cell consortia. First, el...

Protein function relies on sequence, folding, and post-translational modification, and molecular measurements are commonly used to reveal these structural features. Here, we report an alternative approach that represents these molecular features as readily measurable electronic patterns and validate this experimental approach by detecting structura...

We enable microelectronic devices to interrogate biology’s molecular communication, perform computations, and in real time control biological systems, including at several hierarchical levels: proteins, cells, and cell consortia. A key driver is establishing electronic access to and from biology’s native redox networks. First, redox-mediated electr...

Biology uses an electron-based modality that involves reduction and oxidation (redox) reactions, and this redox modality has both molecular and electrical features. Importantly, the electrical features are accessible to convenient electrode measurements, but this electron-based redox modality is fundamentally different from biology’s ion-based elec...

Twenty years ago, this journal published a review entitled "Biofabrication with Chitosan" based on the observations that (i) chitosan could be electrodeposited using low voltage electrical inputs (typically less than 5 V) and (ii) the enzyme tyrosinase could be used to graft proteins (via accessible tyrosine residues) to chitosan. Here, we provide...

The toxicity of paraquat is believed to involve a redox-cycling mechanism that can disrupt cellular redox homeostasis and, also, generate damaging free radicals. It has been suggested that for cases of severe paraquat poisoning the administration of ascorbate (i.e., vitamin C) can confer benefit by quenching the paraquat free radical (PQ+·). Here,...

Electronic materials that allow the controlled flow of electrons in aqueous media are required for emerging applications that require biocompatibility, safety, and/or sustainability. Here, a composite hydrogel film composed of graphene and catechol is electrofabricated, and that this composite offers synergistic properties is reported. Graphene con...

Recent observations that abiotic materials can engage in redox-based interactive communication motivates the search for new redox-active materials. Here we fabricated a hydrogel from a four-armed thiolated polyethylene glycol (PEG-SH) and the bacterial metabolite, pyocyanin (PYO). We show that: (i) the PYO-PEG hydrogel is reversibly redox-active; (...

Catechol-based materials possess diverse properties that are especially well-suitable for redox-based bioelectronics. Previous top-down, systems-level property measurements have shown that catechol-polysaccharide films (e.g., catechol-chitosan films) are redox-active and allow electrons to flow through the catechol/quinone moieties via thermodynami...

Growing evidence implicates an association between psychosocial stress and oxidative stress (OxSt) although there are not yet reliable biomarkers to study this association. We used a Trier Social Stress Test (TSST) and compared the response of a healthy control group (HC; N=10) against the response of a schizophrenia group (SCZ; N=10) that is expec...

Biology uses well-known redox mechanisms for energy harvesting (e.g., respiration), biosynthesis, and immune defense (e.g., oxidative burst), and now we know biology uses redox for systems-level communication. Currently, we have limited abilities to "eavesdrop" on this redox modality, which can be contrasted with our abilities to observe and actuat...

Emerging research indicates that biology routinely uses diffusible redox‐active molecules to mediate communication that can span biological systems (e.g., nervous and immune) and even kingdoms (e.g., a microbiome and its plant/animal host). This redox modality also provides new opportunities to create interactive materials that can communicate with...

Reduction–oxidation (redox) reactions provide a distinct modality for biological communication that is fundamentally different from the more‐familiar ion‐based electrical modality. Biology uses these two modalities for communication through different systems (immune versus nervous), and uses different mechanisms to control the flow of the charge ca...

A catechol‐based molecular memory film is reported by Xiaowen Shi, Gregory F. Payne, and co‐workers in article number 2000452. It is easy to fabricate, employs a simple 2‐state redox mechanism, and is conveniently read by orthogonal optical and electrical measurements. The redox memory states are stable for hours and can be repeatedly switched elec...

Redox is emerging as an alternative modality for bio‐device communication. In contrast to the more familiar ionic electrical modality: (i) redox involves the flow of electrons through oxidation–reduction reactions; (ii) the aqueous medium is an “insulator” to this electron flow since free electrons do not normally exist in water; and (iii) redox st...

Biology uses diffusible oxidants to perform functions that range from signaling to matrix assembly, and these oxidation chemistries offer surprising selectivities. Here, it is reported that mediated electrochemistry can access the richness of such oxidation chemistries. Specifically, electrode‐imposed voltage inputs are used to locally generate oxi...

Melanins are macromolecules that are ubiquitous in nature and impart a large variety of biological functions, including structure, coloration, radiation resistance, free radical scavenging, and thermoregulation. Currently, in the majority of investigations, melanins are either chemically synthesized or extracted from animals, which presents signifi...

Melanins, the main epidermal pigments of man, have been viewed traditionally as performing photoprotective and antioxidant functions, yet increasing evidence indicates they also possess detrimental pro-oxidant activities. Understanding this duality in functional activity (anti- vs. pro-oxidant) is important because oxidative stress is believed to p...

Nanostructured materials offer the potential to drive future developments and applications of electrochemical devices, but are underutilized because their nanoscale cavities can impose mass transfer limitations that constrain electrochemical signal-generation. Here, we report a new signal-generating mechanism that employs a molecular redox capacito...

Bridging communication between biology and electronics is critically dependent on the modality. There have been remarkable successes in bio-device communication through the electrical modality associated with the flow of ions across cellular membranes because this modality is integral to communication in biology (e.g., in neuromuscular systems) and...

Accumulating evidence implicates oxidative stress in a range of diseases, yet no objective measurement has emerged that characterizes the global nature of oxidative stress. Previously, we reported a measurement that employs the moderately strong oxidant iridium (Ir) to probe the oxidative damage in a serum sample and reported that in a small study...

Catechols are abundant in nature and are believed to perform diverse biological functions that include photoprotection (e.g., melanins), molecular signaling (e.g., catecholamine neurotransmitters), and mechanical adhesion (e.g., mussel glue). Currently, the structure-property-function relationships for catechols remain poorly resolved, and this is...

A common bioelectronics goal is to enable communication between biology and electronics, and success is critically dependent on the communication modality. When a bio-relevant modality aligns with instrumentation capabilities, then remarkable successes have been observed (e.g., electrodes provide a powerful tool to observe and actuate biology throu...

Biology is well-known for its ability to communicate through (i) molecularly-specific signaling modalities and (ii) a globally-acting electrical modality associated with ion flow across biological membranes. Emerging research suggests that biology uses a third type of communication modality associated with a flow of electrons through reduction/oxid...

While conventional material fabrication methods focus on form and strength to achieve function, the fabrication of material systems for emerging life science applications will need to satisfy a more subtle set of requirements. A common goal for biofabrication is to recapitulate complex biological contexts (e.g. tissue) for applications that range f...

Polydopamine (PDA) is a bioinspired material and coating that offers diverse functional activities (e.g., photothermal, antioxidant, and antimicrobial) for a broad range of applications. Although PDA is reported to be redox active, the association between PDA’s redox state and its functional performance has been difficult to discern because of PDA’...

Biomacromolecules often possess information to self-assemble through low energy competing interactions which can make self-assembly responsive to environmental cues and can also confer dynamic properties. Here we coupled self-assembling systems to create biofunctional multilayer films that can be cued to dis-assemble through either molecular or ele...

We report a novel strategy for bridging information transfer between electronics and biological systems within microfluidic devices. This strategy relies on our “electrobiofabrication” toolbox that uses electrode-induced signals to assemble biopolymer films at spatially defined sites and then electrochemically “activates” the films for signal proce...

Melanins are ubiquitous in nature, yet their functions remain poorly understood because their structures and properties elude characterization by conventional methods. Since many of melanins’ proposed functions (e.g., antioxidant, pro-oxidant and radical scavenging) involve an exchange of electrons, we developed an electrochemical reverse engineeri...

Recent studies showed that melanin-mimetic catechol-chitosan films are redox-active and their ability to exchange electrons confers pro-oxidant activities for the sustained, in situ generation of reactive oxygen species for antimicrobial bandages. Here we electrofabricated catechol-chitosan films, demonstrate these films are redox-active, and show...

It was brought to our attention that there were errors in the original publication by Kim et al. [1]. [...].

Open wounds and burns are prone to infection and there remains considerable interest in developing safe and effective mechanisms to confer antimicrobial activities to wound dressings. We report a biomimetic wound dressing for the in situ and sustained generation of reactive oxygen species (ROS). Specifically, we fabricate a catechol-modified chitos...

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 integrati...

Biology and electronics are both expert at for accessing, analyzing, and responding to information. Biology uses ions, small molecules, and macromolecules to receive, analyze, store, and transmit information, whereas electronic devices receive input in the form of electromagnetic radiation, process the information using electrons, and then transmit...

Melanins are ubiquitous in nature but their biological activities and functions have been difficult to discern. Conventional approaches to determine material function start by resolving structure and then characterize relevant properties. These approaches have been less successful for melanins because of their complex structure and insolubility, an...

Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins: (i) are redox-active and can rapidly and repeatedly...

Clozapine (CLZ), a dibenzodiazepine, is demonstrated as the optimal antipsychotic for patients suffering from treatment-resistant schizophrenia. Like many other drugs, understanding the concentration of CLZ in a patient's blood is critical for managing the patients' symptoms, side effects, and overall treatment efficacy. To that end, various electr...

Catechols offer diverse properties and are used in biology to perform various functions that range from adhesion (e.g., mussel proteins) to neurotransmission (e.g., dopamine), and mimicking the capabilities of biological catechols have yielded important new materials (e.g., polydopamine). It is well known that catechols are also redox-active and we...

Selectivity presents a crucial challenge in direct electrochemical sensing. One example is schizophrenia treatment monitoring of the redox-active antipsychotic clozapine. To accurately assess efficacy, differentiation from its metabolite norclozapine-similar in structure and redox potential-is critical. Here, the authors leverage biomaterials integ...

We investigate gold, TiN, and platinum in combination with a chitosan–catechol-based redox-cycling system (RCS) for electrochemical detection of the antipsychotic clozapine. We have previously demonstrated the RCS for detection of clozapine in serum, but challenges remain regarding low signal-to-noise ratios. This can be mitigated by selection of e...

Clozapine is one of the most promising medications for managing schizophrenia but it is under-utilized because of the challenges of maintaining serum levels in a safe therapeutic range (1–3 μM). Timely measurement of serum clozapine levels has been identified as a barrier to the broader use of clozapine, which is however challenging due to the comp...

Molecular communication offers an exciting vision for extending the advances of communication technology to the chemical modalities of biology. Realizing this vision is often impeded by the technical difficulties in creating devices capable of sending and/or receiving information that is coded in a specific chemical structure. Here we suggest that...

The ability to interconvert information between electronic and ionic modalities has transformed our ability to record and actuate biological function. Synthetic biology offers the potential to expand communication ‘bandwidth' by using biomolecules and providing electrochemical access to redox-based cell signals and behaviours. While engineered cell...

Matlab script files for the fluorescence synthesis model

Supplementary Figures, Supplementary Tables, Supplementary Notes, and Supplementary References

Oxidative stress is implicated in many diseases yet no simple, rapid and robust measurement is available at the point-of-care to assist clinicians in detecting oxidative stress. Here, we report results from a discovery-based research approach in which a redox mediator is used to probe serum samples for chemical information relevant to oxidative str...

The intestine is the site of digestion and forms a critical interface between the host and the outside world. This interface is composed of host epithelium and a complex microbiota which is "connected" through an extensive web of chemical and biological interactions that determine the balance between health and disease for the host. This biology an...

A hydrogel-based dual film coating is electrofabricated for transducing bio-relevant chemical information into electronical output. The outer film has a synthetic biology construct that recognizes an external molecular signal and transduces this input into the expression of an enzyme that converts redox-inactive substrate into a redox-active interm...

The Information Age transformed our lives but it has had surprisingly little impact on the way chemical information (e.g., from our biological world) is acquired, analyzed and communicated. Sensor systems are poised to change this situation by providing rapid access to chemical information. This access will be enabled by technological advances from...

The acquisition of chemical information is a critical need for medical diagnostics, food/environmental monitoring, and national security. Here, we report an electrochemical information processing approach that integrates (i) complex electrical inputs/outputs, (ii) mediators to transduce the electrical I/O into redox signals that can actively probe...

Parkinson’s disease is a neurodegenerative disorder associated with oxidative stress and the death of melanin-containing neurons of the substantia nigra. Epidemiological evidence links exposure to the pesticide paraquat (PQ) to Parkinson’s disease and this link has been explained by a redox-cycling mechanism that induces oxidative stress. Here, we...

Pheomelanin has been implicated in the increased susceptibility to UV-induced melanoma for people with light skin and red hair. Recent studies identified a UV-independent pathway to melanoma carcinogenesis and implicated pheomelanin's pro-oxidant properties that act through the generation of reactive oxygen species and/or the depletion of cellular...

In order to match our ability to conceive of and construct cells with enhanced function, we must concomitantly develop facile, real-time methods for elucidating performance. With these, new designs can be tested in silico and steps in construction incrementally validated. Electrochemical monitoring offers the above advantages largely because signal...

Clozapine is the most effective antipsychotic drug for schizophrenia treatment, however it is currently 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 and integrative approach of designing a point-of-care device that could e...

When measuring chemical information in biological fluids, challenges of cross-reactivity arise, especially in sensing applications where no biological recognition elements exist. An understanding of the cross-reactions involved in these complex matrices is necessary to guide the design of appropriate sensing systems. This work presents a methodolog...

Mental health disorders are complex and poorly understood but would benefit from real-time chemical analysis capable of assessing a patient's current status, personalizing a therapeutic action, and monitoring compliance. Here, an electrochemical sensor is reported for detecting the antipsychotic drug clozapine which is one of the most effective but...

Individually, advances in microelectronics and biology transformed the way we live our lives. However, there remain few examples in which biology and electronics have been interfaced to create synergistic capabilities. We believe there are two major challenges to the integration of biological components into microelectronic systems: (i) assembly of...

This work presents a thorough electrochemical and reliability analysis of a sensing scheme for the antipsychotic clozapine. We have previously demonstrated a novel detection approach for this redox-active drug, highly effective in schizophrenia treatment, based on a catechol-modified chitosan film. The biomaterial film enables amplification of the...

There are many unresolved questions concerning the health benefits of dietary antioxidants due in part to the complexity of the materials and mechanisms of action. We applied a new electrochemical method and report new observations for one of the richest sources of dietary antioxidants. We observed that the insoluble fraction of clove is redox-acti...

Microelectronic devices that contain biological components are typically used to interrogate biology rather than control biological function. Patterned assemblies of proteins and cells have, however, been used for in vitro metabolic engineering, where coordinated biochemical pathways allow cell metabolism to be characterized and potentially control...

Redox-cycling compounds can significantly impact biological systems and can be responsible for activities that range from pathogen virulence and contaminant toxicities, to therapeutic drug mechanisms. Current methods to identify redox-cycling activities rely on the generation of reactive oxygen species (ROS), and employ enzymatic or chemical method...

Macromolecular phenolics are among the most abundant organic molecules in nature, yet their biological activities are largely unresolved due to their structural complexity and an inability to experimentally probe functionality. We developed thin film and electrochemical methodologies to probe the redox properties of melanin, lignin, and humic acid,...

Sensor‐based chemical analyses commonly enlist either the molecular recognition capabilities of biology (e.g., enzyme biosensors) or advanced information processing algorithms (e.g., the electronic nose). Here, a hybrid approach is proposed in which an enzyme is used to “filter” chemical information and write this information to a film which then s...

This paper reports on an experimental study of the ability to use ascorbic acid as a reducing agent for a clozapine (CLZ) biosensor based on redox cycling electrochemistry. Ascorbic acid, which is naturally present in the blood serum, was related to the current reducing mediator, hexaammineruthenium(III) (Ru). The performance of these two candidate...

It is well-established that redox-reactions are integral to biology for energy harvesting (oxidative phosphorylation), immune defense (oxidative burst) and drug metabolism (phase I reactions), yet there is emerging evidence that redox may play broader roles in biology (e.g., redox signaling). A critical challenge is the need for tools that can prob...

We present the first demonstration of a micro-scale electrochemically-amplifying biosensor for real-time monitoring of the antipsychotic clozapine. The amplification probe consists of a catechol-modified chitosan redox-cycling system, which increases the electrochemical signal generated by clozapine. Modified microelectrodes show a 2.5-fold higher...

We present the first demonstration of an electrochemically-active biomaterial probe for schizophrenia treatment monitoring, and its integration in lab-on-a-chip devices. The probe consists of the naturally derived polymer, chitosan, grafted with catechol to provide a redox cycling system. These modifications to the probe significantly amplify the e...