Hadar Ben-Yoav

Ben-Gurion University of the Negev | bgu · Department of Biomedical Engineering

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...

Particles analysis, such as cell counting and differentiation, are widely used for the diagnosis and monitoring of several medical conditions, such as during inflammation. Three-dimensional-printed lab-on-a-chip (LOC) devices, which can utilize one of the cell counting methods, can bring this technology to remote locations through its cost-efficien...

Microfluidics is a highly useful platform for culturing, monitoring, and testing biological cells. The integration of electrodes into microfluidic channels extends the functionality, sensing, and testing capabilities of microfluidic systems. By employing an electrochemical impedance spectroscopy (EIS) technique, the non-invasive, label-free detecti...

In situ analysis of multiple biomarkers in the body provides better diagnosis and enables personalized health management. Since many of these biomarkers are redox-active, electrochemical sensors have shown promising analytical capabilities to measure multiple redox-active molecules. However, the analytical performance of electrochemical sensors rap...

Classically, the need for highly sophisticated instruments with important economic costs has been a major limiting factor for clinical pathology laboratories, especially in developing countries. With the aim of making clinical pathology more accessible, a wide variety of free or economical technologies have been developed worldwide in the last few...

Designing functional materials as electrode coatings to transduce high‐quality information about redox molecules in biofluids is crucial for developing the next‐generation medical devices. Rapidly analyzing the neurotransmitter dopamine (DA) urinary levels can enable point‐of‐care testing for neuroendocrine tumors. A novel sensing electrodes array...

In article number 2004146, Hadar Ben‐Yoav and co‐workers introduce a sensory device that can test unprocessed urine and quantify dopamine levels. By utilizing intelligent chemometric models for fingerprint identification, the device detects and separates overlapping electrochemical signatures in urine to arrive at its solution. Being able to rapidl...

Hydroxyurea, an oral medication with important clinical benefits in the treatment of sickle cell anemia, can be accurately determined in plasma with a transition metal dichalcogenide-based electrochemical sensor. We used a two-dimensional molybdenum sulfide material (MoS2) selectively electrodeposited on a polycrystalline gold electrode via tailore...

Schizophrenia is a challenging mental health disorder [1]. While various antipsychotics have [...]

This work presents the development of an electrochemical microsystem for antipsychotic clozapine treatment monitoring in schizophrenia patients. In our previous work, we demonstrated clozapine detection directly in spiked whole blood samples of a healthy volunteer using a chitosan-carbon nanotube-modified microelectrode with external counter and re...

We demonstrate a low-cost standalone portable spectrophotometer for fast and reliable measurement execution. The data acquired can be both displayed via a dedicated smartphone application or a computer interface, allowing users either to gather and view data on the move or set up a continuous experiment. All design and software files are open-sourc...

Olanzapine is a thienobenzodiazepine compound. It is one of the newer types of antipsychotic drugs used in the treatment of schizophrenia and other psychotic disorders. Several methods have been reported for analyzing olanzapine in its pure form or combined with other drugs and in biological fluids. These methods include high-performance liquid chr...

Electrochemical sensors based on antibody-antigen recognition events are commonly used for the rapid, label-free, and sensitive detection of various analytes. However, various parameters at the bioelectronic interface, i.e., before and after the probe (such as an antibody) assembly onto the electrode, have a dominant influence on the underlying det...

Antipsychotic clozapine is the most effective medication currently available for schizophrenia. However, clozapine is dramatically underutilized due to its harsh side effects that are not effectively monitored. By continuously monitoring clozapine blood levels, such as use of an implantable glucometer, which has transformed diabetes management, the...

The antipsychotic clozapine is the most effective medication available for schizophrenia and it is the only antipsychotic with a known efficacious clinical range. However, it is dramatically underutilized due to the inability to test clozapine blood levels in finger‐pricked patients' samples. This prevents obtaining immediate blood levels informati...

Cell biosensors have shown great potential for their use in various analytical applications, such as environmental monitoring and biomedical diagnostics. The main aspect of this field is the integration of live sensor cells into miniaturized hardware platforms that enable portability of the integrated system and improve its detection performance. H...

In vivo monitoring of the neurotransmitter dopamine can potentially improve the diagnosis of neurological disorders and elucidate their underlying biochemical mechanisms. While electrochemical sensors can detect unlabeled dopamine molecules, their sensing performance is dramatically reduced by electrochemical currents generated by other, interferin...

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...

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...

Dopamine (DA) is a neurotransmitter located in the ventral tegmental area of the midbrain, the substantia nigra pars compacta, and the arcuate nucleus of the hypothalamus of the human brain [1]. It is a critical puzzle piece in understanding neural behavior and in developing therapeutic intervention technologies for neurological disorders. Monitori...

Dopamine is a neurotransmitter found in several deep structures of the brain. For example, in the ventral tegmental area (VTA) of the midbrain, in the substantia nigra pars compacta, and in the arcuate nucleus of the hypothalamus of the human brain [1]. Dopamine plays a key role during addiction. One hypothesis [2] is that the control of dopamine i...

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...

A microfluidic electrochemical lab-on-a-chip (LOC) device for DNA hybridization detection has been developed. The device comprises a 3 × 3 array of microelectrodes integrated with a dual layer microfluidic valved manipulation system that provides controlled and automated capabilities for high throughput analysis of microliter volume samples. The su...

We present the first in-depth system integration study of in-plane hydrodynamic focusing in a microfluidic impedance cytometry lab-on-a-chip. The method relies on constricting the detection volume with non-conductive sheath flows and characterizing particles or cells based on changes in impedance. This approach represents an avenue of overcoming cu...

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...

A three-dimensional micro-supercapacitor has been developed using a novel bottom-up assembly method combining genetically modified Tobacco mosaic virus (TMV-1Cys), photolithographically defined micropillars and selective deposition of ruthenium oxide on multi-metallic microelectrodes. The three-dimensional microelectrodes consist of a titanium nitr...

Background/Objectives The use of electric fields in combination with small doses of antibiotics for enhanced treatment of biofilms is termed the ‘bioelectric effect’ (BE). Different mechanisms of action for the AC and DC fields have been reported in the literature over the last two decades. In this work, we conduct the first study on the correlatio...

Bacterial biofilms present a societal challenge, as they occur in the majority of infections but are highly resistant to both immune mechanisms and traditional antibiotics. In the pursuit of better understanding biofilm biology for developing new treatments, there is a need for streamlined, controlled platforms for biofilm growth and evaluation. We...

We present the first implementation of osmotic erythrocyte (RBC) lysis for microfluidic leukocyte (WBC) impedance cytometry. The method relies on osmotic pressure differentials to rupture RBC membranes, and detection of WBCs based on changes in impedance. Specifically, we demonstrate an up to 1,200-fold decrease in noise from RBCs in WBC recordings...

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...

Miniaturization of analytical benchtop procedures into the micro-scale provides significant advantages in regards to reaction time, cost, and integration of pre-processing steps. Utilizing these devices towards the analysis of DNA hybridization events is important because it offers a technology for real time assessment of biomarkers at the point-of...

We present the first comprehensive study of integrating hydrodynamic focusing to provide tunable sensitivity and throughput in impedance cytometry. This interplay has never been investigated with respect to particle counting and sizing performance. Our microfluidic lab-on-a-chip (LOC) differs from previous designs in the added tunability while feat...

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...

This work studies miniaturization effects of an electrochemical sensor for TNT detection modified with Tobacco mosaic virus-like particles (VLPs). VLPs have been genetically modified to express peptides that show high binding affinity to TNT. When immersed in a solution containing TNT, modified VLPs bind to the TNT molecules, changing their diffusi...

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...

We present the development of an electrochemical-active biomaterial probe for schizophrenia treatment analysis through redox activity amplification of the antipsychotic clozapine towards its integration in lab-on-a-chip (LOC) devices. The probe consists of the naturally derived polymer chitosan modified with catechol to provide a redox capacitor sy...

Integrated polypyrrole, a conductive polymer, interconnects on polymeric substrates were microfabricated for flexible sensors and actuators applications. It allows manufacturing of moving polymeric microcomponents suitable, for example, for micro-optical-electromechanical (MOEMS) systems or implanted sensors. This generic technology allows producin...

This work demonstrates the first utilization of virus molecules as nano-scale biotemplates assembled on an electrochemical biosensor, allowing for an 8-times increased signal and an improved biosensing performance of 9.5-fold. The versatile and inexpensive biological Tobacco mosaic virus was integrated as a high aspect ratio, low footprint, low-cos...

We present the first demonstration of a novel bacterial biofilm treatment technique showing a 56% average decrease in bacterial cell viability compared to traditional antibiotic treatments in a Micro-BOAT platform. Integrated linear array charge-coupled devices achieve spatially realized optical density monitoring, correlating to both average bioma...

DNA hybridization detection in microfluidic devices can reduce sample volumes, processing times, and can be integrated with other measurements. However, as device footprints decrease and their complexity increase, the signal-to-noise ratio in these systems also decreases and the sensitivity is thereby compromised. Device miniaturization produces di...

Integrated conductive polymer (Polypyrrole, PPy) features were micro-fabricated on polymeric substrates for flexible sensor and actuator applications. Such structures allow manufacturing of moving polymeric micro components suitable, for example, for Micro Electro Mechanical Systems (MEMS), Micro Optical Electro Mechanical Systems (MOEMS) or implan...

In this article the research for developing whole-cell biochips has been presented using both bioluminescent and electrochemical methods. The research was on integrating an electrode cell with both electrochemical and bioluminescent detection using a single VLSI chip. The authors have investigated the signal conditioning system that can work with a...

Cell-based toxicity bioassays harbor the potential for efficient detection and monitoring of hazardous materials. However, their use in the field has been limited by harsh and unstable environmental conditions that shorten shelf-life, introduce significant noise, and reduce the signal and signal-to-noise ratio; such conditions may thus decrease the...

Bacterial cells attachment onto solid surfaces and the following growth into mature microbial biofilms may result in highly antibiotic resistant biofilms. Such biofilms may be incidentally formed on tissues or implanted devices, or intentionally formed by directed deposition of microbial sensors on whole-cell bio-chip surface. A new method for elec...