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New Trends in Biomedical Devices


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The "KAUST Research Conference on New Trends in Biosensors and Bioelectronics" aims to give an overview of the most recent efforts in bioelectronics that address the "interface" problem and overcome the limits of the current technologies by generating new materials, implementing novel architectures or developing innovative devices.








Location


Conference Center (Building 19), Level 3, Conference Hall 1 


Conference Schedule

  • MondayFebruary 25
  • TuesdayFebruary 26
  • WednesdayFebruary 27
7:15 AM

Registration & Breakfast

8:45 AM

Welcome address & Introductory remarks

9:15 AM

Optical Biosensors and Systems Integration: Past, Present and Future

Optical biosensors rely on a biological or biomimetic molecule to accomplish a molecular recognition event, generate an optical signal when that recognition event occurs, and measure the signal with a photonic device. Within that definition, there is a broad spectrum of means for realizing each of the three main steps. The most frequently used recognition molecules include antibodies, enzymes, aptamers, oligonucleotides and synthetic peptides, but assemblies of molecules as complex as living cells are also used. Methods for transducing the recognition event into an optical signal can employ methods as simple as measuring a change in optical density to multicomponent amplification cascades and molecular machines. Finally, there must be a portable method for measuring the optical signal; your eye might be considered a portable readout device, but a large laboratory microscope is not. When creating a biosensor, all three parts of the system must work in concert and be appropriate for the user’s needs. Biosensor systems integration is key to the design of a practical system. The information provided must be at the level of sensitivity, specificity, quantitative accuracy and level of complexity on which a decision can be based. I will provide examples of several biosensors used outside the laboratory and how variables such as reagent stabilization, resistance to fouling, automation, energy use, system footprint, and user needs were incorporated into the design. Since the biosensors just described were commercialized, the biosensor community has explored new approaches for molecular recognition and exciting technologies for signal measurement, many of which will be addressed in detail by the other speakers in this conference. Some of the most exciting of these advances include single molecule measurements, visually detectable amplified color schemes, automation of sample processing using microfluidic systems, simplified separations and sample transport using paper, and signal readout using cell phone optics. Examples from my collaborations will be briefly introduced: e.g. programmable paper pumps and continuously operating in vivo sensors. Opportunities for the future are limited only by the imagination. The use of small robotics and telecommunications enable consortium measurements across extended areas or populations. Inexpensive and miniaturized electronics and optics enable the use of biosensors for environmental and agricultural applications. Simplified components and well defined criteria for materials and recognition molecules enable low cost applications for single-use point-of-care and continuous-use wearable diagnostic devices for both human and animal health.

Frances  S. Ligler
Department of Biomedical Engineering, UNC-Chapel Hill and NC State University
10:00 AM

Flexible bioelectronics on a thread: sensors, microfluidics, electronics and drug delivery

This talk will explore the new realm of using threads as an ultimate platform for flexible and stretchable bioelectronics. Threads offer unique advantages of universal availability, low cost, material diversity and simple textile-based processing. In this talk, I will report reel-to-reel fabrication to make functional smart threads for variety of sensing and electronics application. For example I will report on nanomaterial-infused smart threads for strain and temperature sensing. Threads will be presented for sensing pH, glucose, and other chemical biomarkers. Interestingly, threads also provide an ideal platform for passive microfluidic sampling and delivery of analytes. I will show our recent work on using this toolkit of thread-based microfluidics, sensors and electronics for application as surgical sutures and flexible smart bandages for chronic wounds. Our recent work on using threads for closed loop spatiotemporal dosage controlled drug delivery will also be presented. If there is time, I will present some related research activities on ingestible devices for studying the gut microbiome, and on flexible microneedles for transdermal drug delivery.

Sameer Sonkusale
Electrical and Computer Engineering, Tufts University
10:30 AM

Coffee Break

10:45 AM

Lab on CMOS Biosensors for Minimally Invasive Health Monitoring

Lab-on-a-chip (LOC) systems are miniaturized devices that integrate several laboratory functions onto a single “chip”. The “chips” in LOC systems are usually passive substrates, so most LOC systems are typically used in conjunction with benchtop equipment for sensing and control. By integrating active electronics into traditional passive LOC systems, a new class of highly integrated multiphysics lab-on-CMOS (LOCMOS) systems has emerged that places instrumentation in intimate contact with sensing and actuation capabilities. The integration of sensing with signal processing, detection, and actuation reduces the need for external instrumentation, leading to overall systems with significantly smaller size and also the potential for completely novel measurements that cannot be performed using traditional approaches. Such devices have the potential to introduce significant and disruptive changes in healthcare diagnosis and delivery in the near future. This talk will provide an overview of emerging LoCMOS biosensors that have been designed to monitor diagnostic biomedical signals, including the detection of neuromuscular activation, biochemical analytes, and optical assays, and also progress that has been reported in the integration of these sensors into biomedical devices. The integration of diagnostic sensors into biomedical devices poses a number of distinct and vexing challenges, including packaging, surface fouling, sterilization, communication, and system power.  Finally, we’ll describe two diagnostic biomedical applications for LoCMOS: 1) a cancer box that aims to extend LoCMOS into an implantable diagnostic device to isolate and contain cancer cells for the purpose of measuring their viability and in vivo response to chemotherapeutic agents; and 2) an ingestible pill that measures biochemical signals in the digestive tract.

Pamela  Abshire
Department of Electrical and Computer Engineering, Institute for Systems Research, University of Maryland
11:15 AM

Recent Advances in Electrochemical Biosensors Based on Molecularly Imprinted Polymers and Nanomaterials

Molecularly imprinted polymers (MIPs) are considered as stable polymers with molecular recognition abilities, provided by the presence of a template during their synthesis. They are generally used to mimic the natural biological receptors used such as antibodies and enzymes. MIPs offered various advantages such as robust, with high stability, required low-cost preparation, and great specific recognition ability with a good sensitivity towards the targeted analyte. Molecularly imprinted polymers based electrochemical sensors were applied for the detection of various kinds of analytes from small molecule such as metals ions and amino acids to much larger proteins, bacteriophage and microbial cells. Owing to their high conductivity, magnetic nanoparticles (MNPs), graphene oxides, multi/single-walled carbon nanotubes (MWCNTs/SWCNTs), and carbon dots are introduced within the MIP films leading to a great sensitivity enhancement of the MIP biomimetic sensors. Magnetite nanoparticles (Fe 3 O 4 NPs) were widely used due to their separation and pre-concentration properties in combination with the molecularly imprinted polymer, which can capture and bind selectively the target analyte. Magnetic molecularly imprinted polymer modified screen printed carbon electrode (Fe3O 4 -MIP/SPCE) combined with various kind of nanomaterials are usually characterized electrochemically using cyclic voltammetry and electrochemical impedance spectroscopy in presence of redox probe such as solution of ferri-ferrocyanide. In this conference, I will present a general overview on the recent advances related to the combination of MIPs and nanomaterials for electrochemical sensing. I will discuss the experimental results obtained with biomimetic sensors based on molecularly imprinting polymers for the detection of emerging pollutants including drugs such as sulphonamides and 17-ß estradiol and endocrine disruptors such as bisphenol A at trace level in various environmental matrices. Furthermore, development of label-free electrochemical sensor based on spore-imprinted polymer for Bacillus cereus spore detection and the effect of ultrasonication on reducing time of MIPs synthesis will be discussed.

Aziz Amine
Laboratory of Chemical Engineering and Environment, Faculty of Sciences and Techniques, Hassan II University of Casablanca, Morocco
11:45 AM

Lunch

1:30 PM

Interfacing with the Brain Using Organic Electronics

One of the most important scientific and technological frontiers of our time is the interfacing of electronics with the human brain. This endeavour promises to help understand how the brain works and deliver new tools for diagnosis and treatment of pathologies including epilepsy and Parkinson’s disease. Current solutions, however, are limited by the materials that are brought in contact with the tissue and transduce signals across the biotic/abiotic interface. Recent advances in organic electronics have made available materials with a unique combination of attractive properties, including mechanical flexibility, mixed ionic/electronic conduction, enhanced biocompatibility, and capability for drug delivery. I will present examples of novel devices for recording and stimulation of neurons and show that organic electronic materials offer tremendous opportunities to study the brain and treat its pathologies.

George  Malliaras
Electrical Engineering Division, University of Cambridge
2:15 PM

Ultra-Miniaturized, Implantable and Wireless Data Acquisition and Actuation Systems

Authors: Ralph Etienne-Cummings (presenter), Jie Zhang and Adam Khalifa
Abstract:
There are many situation where substantial high-resolution data must be communicated over low bandwidth channels. These include ubiquitous distributed video, implanted high-density neural recordings, gastric monitoring ePills, and other such power constrained systems. To meet the communication specification of these systems, significant signal processing is required at the sensor in order to extract relevant information and/or to compress the data that must be communicated. Compressed sampling and reconstruction provide an efficient way to squeeze large amount of data into the narrow communication pipes. For example, we show that we can recover 100 frames of video from a single coded frame without motion blurring. We also show that the coded video can used for image enhancement, object recognition and other image processing even before reconstruction. On the neural recording front, we show high levels of compression that preserve both spike timing information and inter-spike signal integrity. This talk will show how compressed sampling and reconstruction can be used to can be used to communicate video and neural signals in these cases. Furthermore, we will show how ultra-miniaturized wireless cameras and implantable neural recording/stimulation devices take advantage of this method. Lastly we will discuss how this technology can be used to develop distributed, un-tethered sensing and actuation modules that can be injected through out the body to monitor a variety of biomarkers for personalized healthcare systems.

Ralph  Etienne-Cummings
Department of Electrical & Computer Engineering, Johns Hopkins University
2:45 PM

Epileptic Seizures: Can Deep Learning Meets Predicting Expectation?

Epilepsy is one of main neurological disorders. Less than 3% of patients only can benefit from surgery. Also, presurgical monitoring to localize the focus is a challenging step. Wearable and implantable brain-machine interfaces (BMIs) are introduced to face the localization of the seizure zone, its onset detection, and abortion of seizures before their emergence. On the other hand, on line prediction of seizures at least a half hour before its appearance is major challenges due to the complexity of brain behavior. This talk includes the description of a wearable helmet based on a fNIRS platform which is composed of an array of system-in-package based optodes proposed to measure hemoglobin variation in deep cortical levels. If a seizure is located but surgery cannot be accomplished, a multichannel mixed-signal detector and stimulator can be used to onset abort the seizures. Most important, prediction based on deep-learning algorithms is creating hope and significant expectation, that allow to prevent seizure while before its onset zone. Several research groups are conducting deep learning implementations to validate predicting algorithms using regular and intracortical EEGs to identify generators of seizure activity.

Mohamad Sawan
Center for Biomedical Research and Innovation, Westlake University, China
3:15 PM

Coffee Break

3:30 PM

Carbon and the Future of Multi-Modal Neural Interfaces

Carbon is fast becoming a leading material of choice in micro and nanofabrication of a variety of sensors, actuators, microelectrodes, wires, batteries, fuel cells, thin-films, and neural interfaces. Its unique tunable mechanical and electronic properties enabled by the availability of a range of possible hybridized bonds (sp2 and sp3) make it a versatile material. Further, carbon has a potential to assume even more far-reaching importance with discovery of newer carbon forms and allotropes such as graphene (excellent conductivity and strength), patternable glassy carbon (excellent electrochemistry), Q-carbon (excellent hardness) and compressed glassy carbon (excellent strength). Research progress in devices that interface with the human body, particularly with the CNS (central nervous system) and PNS (peripheral nervous system) continues, with two key application areas, i.e., (i) BCI (cortical and spinal neuroprosthetics) and (ii) bioelectronics (treating chronic conditions through electrical stimulation of vagus nerves, emerging as promising areas for clinical translation. Against this background, carbon’s excellent conductivity, robust electrochemical activity as well as homogenous microstructure offer a very more compelling in-vivo platform for multi-modal neural interfaces for extended period of implantation. In this talk, therefore, we report a new class of carbon-based neural probes that consist of homogeneous glassy carbon (GC) microelectrodes, interconnects and bump pads with superior electrochemical properties, in-vivo performance and long-term stability under electrical stimulation. These electrodes have purely capacitive behavior with exceptionally high charge storage capacity (CSC) and are capable of sustaining more than 3.5 billion cycles of bi-phasic pulses at charge density of 0.25 mC/cm2. Extensive in-vivo and in-vitro tests confirmed: (i) high SNR (>16) recordings, (ii) highest reported CSC for non-coated neural probe (61.4± 6.9 mC/cm2), (iii) high-resolution dopamine detection (10 nM level - one of the lowest reported so far), (iv) recording of both electrical and electrochemical signals, and (v) no failure after 3.5 billion cycles of pulses. Supported by characterizations and computational modeling results, the talk will demonstrate (i) the reason behind long-term corrosion problems in thin-film metal microelectrodes and the promise of homogenous electrode material such as GC and (ii) the microenvironment and response of tissues to long-term electrical stimulations. In this talk, we will also introduce some of the key research activities being carried out at CSNE (Center for Sensorimotor and Neural Engineering), NSF-funded Engineering Research Center with University of Washington, MIT, and San Diego State University (SDSU) as leading institutions.

Sam  Kassegne
Department of Mechanical Engineering, San Diego State University
4:00 PM

Electrophoretic drug delivery for seizure control

Speaker: Chris Proctor
University of Cambridge

4:15 PM

Panel on Implantable sensors: challenges and opportunities


George  Malliaras
Electrical Engineering Division, University of Cambridge
Mohamad Sawan
Center for Biomedical Research and Innovation, Westlake University, China
Ralph  Etienne-Cummings
Department of Electrical & Computer Engineering, Johns Hopkins University
Guglielmo  Lanzani
Department of Physics, Politecnico di Milano
5:00 PM

End of Day 1

7:00 PM

Welcome Dinner

By invitation only.

7:45 AM

Breakfast

9:00 AM

KAUST Office of Sponsored Research

9:15 AM

Nanosystems for Food, Drug and Biomedical Applications

Nanotechnology allows for the unique design and functionalization of materials and devices at the nanometer scale for a variety of applications. Our laboratory has fabricated nanosystems for drug screening, in vitro toxicology, sample preparation, diagnostic, and food pathogen detection. The miniaturized devices allow for the rapid and automated processing of drug candidates, clinical and food samples in tiny volumes, greatly facilitating drug testing, genotyping assays, infectious disease detection, cancer diagnosis, point-of-care monitoring, and food testing. For example, we have designed plasmonic nanocrystals for single nucleotide polymorphism (SNP) genotyping. The platform involves polymerase chain reaction (PCR) for target sequence amplification and colorimetric detection with nanoprobes for pharmacogenomics applications. We have also established polymer-based lab-on-a-cartridge for automated sample preparation and PCR detection. The integrated all-in-one system, termed MicroKit, allows for the rapid and accurate typing and subtyping of influenza and other viral infections within 2 hours. We have further developed sophisticated lab-on-a-chip system that enables us to achieve multiplexed detection of drug-resistant bacteria and food pathogens. We have created the silicon-based Microsieve system for the rapid and selective isolation of circulating tumor cells (CTCs) from peripheral blood. This non-invasive, near real-time, inexpensive liquid biopsy approach allows for the enumeration and biomarker analysis of CTCs for cancer diagnosis, prognosis and monitoring. We have also established paper-based assays for the rapid detection of various diseases, such as Dengue, Zika, hepatitis and sexually transmitted diseases. In addition, these inexpensive test kits can be used for food pathogen detection and meat speciation.

Jackie Ying
NanoBio Lab, Singapore
10:00 AM

Microfluidic sorting of sperm for applications in Assisted Reproductive Technologies

Micro- and nano-scale technologies can have a significant impact on medicine and biology in the areas of cell manipulation, diagnostics and monitoring. At the convergence of these new technologies and biology, we research for enabling solutions to real-world problems at the clinic. Emerging nano-scale and microfluidic technologies integrated with biology offer innovative possibilities for creating intelligent, mobile medical lab-chip devices that could transform diagnostics and monitoring, tissue engineering and regenerative medicine. Male infertility is a reproductive disease, and existing clinical solutions for this condition often involve long and cumbersome sperm sorting methods, including preprocessing and centrifugation‐based steps. These methods also fall short when sorting for sperm free of reactive oxygen species, DNA damage, and epigenetic aberrations. Existing platforms suffer from structural complexities, i.e., pumps or chemoattractants, setting insurmountable barriers to clinical adoption. Inspired by the natural filter‐like capabilities of the female reproductive tract for sperm selection, a model‐driven design—featuring pillar arrays that efficiently and noninvasively isolate highly-motile and morphologically normal sperm, with lower epigenetic global methylation, from raw semen—is presented. The microfluidic sperm sorters that we created, such as the Simple Periodic ARray for Trapping And isolatioN (SPARTAN), modulate the directional persistence of sperm, increasing the spatial separation between progressive and non-progressive motile sperm populations. They lead to results within an unprecedentedly short 10-minute assay time. With over 99% motility of sorted sperm, a 5‐fold improvement in morphology, 3‐fold increase in nuclear maturity, and 2–4‐fold enhancement in DNA integrity, SPARTAN offers to standardize sperm selection while eliminating operator‐to‐operator variations, centrifugation, and flow. Some of these innovative microfluidic devices have been translated into FDA approved and CE-marked products, where they have been widely used by fertility clinics around the world to serve patients, leading to an estimated 10,000+ live births globally.

Utkan  Demirci
Department of Electrical Engineering, Standford University
10:30 AM

Coffee Break

10:45 AM

Ultra-Sensitivity in PT-Symmetric Non-Hermitian Radio-Frequency Biosensors

Internet-of-things (IoTs) composed of a large number of radio-frequency (RF) microsensors, with advantages like low cost and extreme miniaturization, could ever have an impact on healthcare, automotive, and industrial landscapes. However, given by their small physical sizes, improving the detection limit of compact, fully-passive RF wireless sensors is often hindered by the low quality-factor (Q-factor) and poor sensitivity. In the first part of my talk, I will discuss how the concept of parity-time (PT) symmetric non-Hermitian Hamiltonian, first proposed in quantum mechanics, can be applied to electromagnetic systems for realizing miniature RF biosensors with ultrahigh Q-factor and singularity-enhanced sensitivity. In the second part of my talk, I will present novel higher-order PT-symmetric telemetric systems, which could provide sensitivity far beyond the state-of-the-art wireless intracular sensors and could achieve the reliable wireless power transfer for implantable and wearable devices. ​

Pai-Yen Chen
Department of Electrical and Computer Engineering, University of Illinois
11:15 AM

Engineering Supramolecular Plasmonic Structures for Detection of MERS- CoV Antigen and “Single Point” Amino Acids Mutation

Specific amino acid substitution has been associated with the instability of peptides and the formation of insoluble amyloid. Established experimental techniques to detect peptide mutations is either destructive or requires rigorous molecular labeling. We present a non-invasive and label-free detection method of amino acid substitution in primary peptide fragments. By optimizing a binary optical identification tag which encodes the Raman vibrational signals of amino acids and peptides, we can extract the structural components of the mutated peptide. A sensor design consisting of plasmonic nanostructures immobilized on an omniphobic surface is used to amplify the Raman signal. We demonstrate a tagging system which can detect a single point missense mutation in 25-35 Aβ fragment and a frameshift mutation in 1-42 Aβ fragment down to the picomole level. This work provides a potential strategy to produce optical identification tags which delivers sensitive and specific molecular information for biosensing.

Niveen M. Khashab
Associate Professor, Physical Science and Engineering, KAUST
11:45 AM

Lunch

1:30 PM

Organic light actuators for non-genetic optical stimulation

Current implant technology exploits electrical signaling at the electrode-neural interface.  This approach has fundamental problems which limit both the performance and safety of the implants, bearing high  invasiveness. Inducing light sensitivity in living organisms is an alternative approach that provides ground breaking opportunities in neuroscience. Optogenetics is a spectacular demonstration of this, yet limited by the viral transfection of exogenous genetic material. In this talk I will describe alternative approaches aimed at NON-genetically inducing light sensitivity in cells or organism by using light-responsive nanostructures (0.1-1 um) or molecular actuators  that trigger signaling cascades.  The photophysics of the actuators is fully characterized, both in vitro as well in vivo, and their effect on cells investigated.

Guglielmo  Lanzani
Department of Physics, Politecnico di Milano
2:15 PM

Soft photonics: Can we design them for biointegrated applications?

The impact of photonic technologies on the health sector is difficult to foresee. While scalpels will not be replaced with lasers, photonic devices promise to be able to make a difference. From artificial retinae; optogenetics, where lasers or light-emitting diodes are used to stimulate or suppressed the firing of neurons; to non-destructive optical sensing in, e.g., pharmacology applications, a high demand exist for versatile, adaptive photonics systems compatible with the soft tissue environment. We will present recent efforts to design new plastics of desired photonic and electronic functions targeted for biointegrated photonics. One line of our enquiry is to explore the potential of new polymer-based systems that can offer the same flexibility, softness and light weight as commodity plastics but can control the flow of light therefore assisting light harvesting, light out-/in-coupling, and or light-wave guiding. Other opportunities for such systems include photonic near-infrared mirrors that could prevent undesired heat built up of specific human tissues but also could prove to be very useful in fighting counterfeits of pharmaceutical products via optical means. Extension to architectures for a range of sensor platforms will also be presented.

Natalie Stingelin
Functional Organic Materials, Georgia Institute of Technology
2:45 PM

Plastic Electrochemical Devices for Biosensing: from Wearables to Screening Antimicrobial Compounds

Organic semiconductors have been traditionally developed for making low-cost and flexible transistors, solar cells and light-emitting diodes. In the last few years, emerging applications in health case and bioelectronics have been proposed. A particularly interesting class of materials in this application area takes advantage of mixed ionic and electronic conduction in certain semiconducting polymers. Indeed, the ability to transduce ionic fluxes into electrical currents is useful when interacting with living matter or bodily fluids. The continuous monitoring of human health can greatly benefit from devices that can be worn comfortably or seamlessly integrated in household objects, constituting “health-centered” domotics. I will describe electrochemical transistors that detect ionic species either directly present in body fluids or resulting from a selective enzymatic reaction (e.g. ammonia from creatinine) at physiological levels. Additionally, I will show that non-charged molecules can be detected by making use of custom-processed polymer membranes that act as “synthetic enzymes”. Using these membranes in conjunction with electrochemical transistors we demonstrate that we are able to measure physiological levels of cortisol in real human sweat. Finally, I will show a more biomimetic approach where the sensing layer is a lipid membrane stabilized at a liquid-liquid interface, which we use to detect antimicrobial compounds.

Alberto Salleo
Department of Materials Science & Engineering, Stanford University
3:15 PM

Coffee Break

3:30 PM

Engineering Conjugated Polymers for Biosensing

Conducting both ionic and electronic charge carriers, conjugated polymers are impacting on a large variety of biology-related applications as the electronic material interfacing with living systems. A device type that has predominantly utilized these polymers as its active component is the organic electrochemical transistor (OECT) – an electrolyte gated transistor used for ionic-to-electronic signal transduction. In this talk, I will show a comprehensive study on the thin film properties of a series of conjugated polymers and evaluate how systematic chemical modifications impact on the electrochemical activity of these materials, thereof the device operation. I will demonstrate the importance of characterizing the properties of these films in-situ for drawing conclusions related to their performance. I will present two cases where modifications in the chemistry of materials are the key for developing OECTs that can detect metabolites in bodily fluids or pick up signals from lipid bilayers. Highlighting the materials properties that enable operation in electrolytes and improve communication with biological systems, this work provides an understanding of materials-device performance relations for the development of next generation organic bioelectronic devices.

Speaker: Sahika Inal

4:00 PM

Ultrafast Responsive Photo Mechanical Molecular Switch Allows Modulation of the Cell Membrane Potential

Speaker: Giuseppe Paterno
Politecnico di Milano

4:15 PM

Panel on Personalized Medicine


Utkan  Demirci
Department of Electrical Engineering, Standford University
Frances  S. Ligler
Department of Biomedical Engineering, UNC-Chapel Hill and NC State University
Jackie Ying
NanoBio Lab, Singapore
Magnus  Berggren
Department of Science and Technology, Division of Physics and Electronics, Linköping University
5:00 PM

End of Day 2

7:00 PM

Poster Session and Buffet Dinner

7:45 AM

Breakfast

9:00 AM

Core Labs: A shared research facility at KAUST

9:15 AM

Organic Bioelectronics – Nature Connected

Organic electronic materials exhibit an array of desired characteristics making them excellent as the signal translator across the gap between biology and technology. These biocompatible materials, often complexed with polyelectrolytes and other functional materials, can be included in device structures, which are flexible, stretchable and even gelled, and can also process electronic, ionic and charged biomolecules in combination. This makes the organic electronic materials unique in several respects to record and regulate functions and physiology of biological systems. Here, a short review of some of the recent progresses from the Laboratory of Organic Electronics is given. In the BioComLab effort, a body area network is used to “connect” electronic skin patches with drug delivery components. This system provides a feedback system, also connected to the cloud for future healthcare. Sensors, converting biochemical signals into electric ones, are typically built up from organic electrochemical transistors and selectivity is typically provided from receptor mediation and oxidase approaches. Conversely, the organic electronic ion pump, converts an electronic addressing signal into the delivery of specific biomolecules, such as a neurotransmitter, to actuate and control functions of for instance the neuronal system. With the BioComLab technology the wide array of neuronal disorders and diseases are targeted, such as epilepsy, Parkinson’s disease and chronical pain. In the e-Plant effort, the BioComLab technology is applied to the plant kingdom to record and impact the signaling pathways of phytohormones, thus allowing us to regulate the growth and expression of specific components of flowers and trees. Further, organic electronic materials can also be applied from aqueous solution directly into the biological system, thus enabling a unique approach to manufacture devices and electrodes in vivo. We are currently exploring this in vivo-manufacturing concept in several settings to define devices and circuits in various plants, to generate a seamless interface between Organic Bioelectronics and biological systems, in general.

Magnus  Berggren
Department of Science and Technology, Division of Physics and Electronics, Linköping University
10:00 AM

Soft electronic and robotic systems from resilient yet biocompatible and degradable materials

Nature inspired a broad spectrum of bio-mimetic systems – from soft actuators to perceptive electronic skins – capable of sensing and adapting to their complex erratic environments. Yet, they are missing a feature of nature’s designs: biodegradability. Soft electronic and robotic devices that degrade at the end of their life cycle reduce electronic waste and are paramount for a sustainable future. At the same time, medical and bioelectronics technologies have to address hygiene requirements. We introduce materials and methods including tough yet biodegradable hydrogels for soft systems that facilitate a broad range of applications, from transient wearable electronics to metabolizable soft robots. These embodiments are reversibly stretchable, are able to heal and are resistant to dehydration. Our forms of soft electronics and robots – built from resilient biogels with tunable mechanical properties – are designed for prolonged operation in ambient conditions without fatigue, but fully degrade after use through biological triggers. Electronic skins merged with imperceptible foil technologies provide sensory feedback such as pressure, strain, temperature and humidity sensing in combination with untethered data processing and communication through a recyclable on-board computation unit. Such advances in the synthesis of biodegradable, mechanically tough and stable iono-and hydrogels may bring bionic soft systems a step closer to nature.

Martin  Kaltenbrunner
Soft Matter Physics Department, Soft Electronics Laboratory, Johannes Kepler University
10:30 AM

Coffee Break

10:45 AM

Organic Bioelectronics from a Molecular Design Perspective

The organic electrochemical transistor (OECT), capable of transducing small ionic fluxes into electronic signals in an aqueous environment, is an ideal device to utilise in bioelectronic applications. To date, nearly all OECTs have been fabricated with commercially available PEDOT:PSS, heavily limiting the variability in performance. We have recently shown that tailor-made semiconducting polymers are fully capable of matching the performance of PEDOT:PSS. To capitalise on this discovery and the versatility of the organic chemistry toolbox, further materials development is needed. In my talk I will discuss our recent work in this area covering examples of both molecular and polymeric semiconducting materials and their performance in bioelectronic devices.

Christian Nielsen
Materials Research Institute and School of Biological and Chemical Sciences, Queen Mary University of London
11:15 AM

Polymeric bioelectronic materials for neural interfacing and regenerative engineering

Direct measurement and stimulation of ionic, biomolecular, cellular, and tissue-scale activity is a staple of bioelectronic diagnosis and/or therapy. Such bi-directional interfacing can be enhanced by a unique set of properties imparted by organic electronic materials. These materials, based on conjugated polymers, can be adapted for use in biological settings and show significant molecular-level interaction with their local environment, readily swell, and provide soft, seamless mechanical matching with tissue. At the same time, their swelling and mixed conduction allows for enhanced ionic-electronic coupling for transduction of biosignals. These properties serve to enable new capabilities in bioelectronics. In the first part of my talk I will focus on the design of polymer bioelectronic materials for enhanced electrophysiological sensors based on electrochemical transistors. Synthetic design and processing can yield stable and high performance mixed conductors with high volumetric capacity, high transconductance, and steep subthreshold switching characteristics for low power sensing. I demonstrate their use in human EEG sensing as a test case. I will then discuss the unique form factors enabled by polymer electronics, and the development of conducting hydrogels for applications in regenerative engineering. The composite hydrogel shows osteoinductive effects on cultured rat primary bone marrow stromal cells in vitro. These results are promising towards passive and active bone growth stimulation for healing non-union fractures and spinal fusion. The applications highlighted demonstrate the versatility of polymer-based bioelectronics, including their ability to amplify low-lying biosignals, and their non-conventional form factors. New materials design will continue to fill critical need gaps for challenging problems in bioelectronic interfacing.

Jonathan  Rivnay
Department of Biomedical Engineering, Northwestern University
11:45 AM

Mixed Conduction in Conjugated Polymers

Speaker: Achilleas Savva
KAUST

12:00 PM

Lunch

1:30 PM

Magnetic Nanowires - Wireless Bio Transducers

Unique features of magnetic nanowires render them attractive materials for biomedical transducer applications. Due to the high aspect ratio, they are characterized by single magnetic domain properties, which can be exploited by electromagnetic interrogation. This allows utilizing such nanowires as remotely operated nanorobots, i.e. induce motion, produce heat or sense their location. Their versatility is further enhanced by surface functionalization, making them cell-specific targeting agents or drug delivery vehicles.
Magnetic nanowires are fabricated by a facile and efficient method using electrodeposition into nanoporous membranes. Iron nanowires are highly biocompatible, and they can be further optimized by annealing, resulting in nanowires with an iron core, an iron oxide shell and tailored magnetization. In combination with polymer matrices, nanowires are employed as ultra-low power flow sensors, for realizing bioinspired artificial skins with tactile sensing capabilities, or to trigger remotely controlled drug delivery particles. Magnetic nanowires are readily internalized by cells via phagocytosis. When applying an alternating magnetic field, they kill cancer cells by a magnetomechanical effect. When further functionalizing the nanowires with drugs, they deliver these drugs into cells, and a combined treatment effect can be obtained together with a magnetic field and/or laser irradiation. The later exploits a photo-thermal effect, that utilizes the near infrared light absorption of iron oxide. Surface coating with antibodies give nanowires specific targeting capabilities, as will be shown for the case of anti-CD44 antibodies to target leukemic cells. The nanowires also have excellent properties as magnetic resonance imaging contrast agents, providing high transverse magnetic relaxivities. This enables high-resolution cell tracking in combination with their manipulation.
Nanostructured substrates for cell growth can be produced, when partially releasing the nanowires from the nanoporous membranes. Due to mimicking the mechanical properties of cellular environments, stem cells growing on top of such substrates show alterations in their differentiation behavior. Thereby, nanowire dimensions modify the stiffness of the cellular environment, affecting the cells’ behavior. A mechanical stimulus can be applied via activating the substrate by an electromagnetic field, providing means for additional manipulations of the cell faith. Differentiation of mesenchymal stem cells into osteoblasts can be achieved on such substrates by electromagnetically induced mechanical stimuli within a few days. With the growing relevance of nanomaterials in biomedical applications, multi-functionality of nanoprobes is being discovered and exploited. Combining a high capacity for functionalization, with diagnostic capabilities and therapeutic functions, iron nanowires are ideal candidates for these theranostics approaches.

Speaker: Jurgen Kosel

2:00 PM

Dimensionality matters in biointerfaces

Fabrizio Pennacchio, Leonardo Garma, Laura Matino, Francesca Santoro
Italian Institute of Technology, 80125, Italy

The interface between biological cells and non-biological materials has profound influences on cellular activities, chronic tissue responses, and ultimately the success of medical implants and bioelectronic devices. For instance, electroactive materials in contact with cells can have very different composition, surface topography and dimensionality. Dimensionality defines the possibility to have planar (2D), pseudo-3D (planar with nano-micropatterned surface)[1] and 3D conductive materials (i.e. scaffolds) in bioelectronics devices. Their success for both in vivo and in vitro applications lies in the effective coupling/adhesion of cells/tissues with the devices’ surfaces. It is known how a large cleft between the cellular membrane and the electrode surface massively affects the quality of the recorded signals or ultimately the stimulation efficiency of a device.

However, this field is hindered by lack of effective means to directly visualize in 3D cell-material interface at the relevant length scale of nanometers. In this work, we explored the use of ultra-thin plasticization technique[2] to cells for the first time on materials which differ in dimensionality[3], particularly focusing on the optimization of this procedure for 3D cell-materials interfaces which have been unexplored so far. We have characterized how cells differently elongate and deform their membranes in response to the dimensionality of the electroactive materials and the relevant processes at the biointerface. In this way, we are able to define a set of optimal conditions for cell-chip coupling which enable an appropriate approach for designing bioelectronics platforms for both in vivo and in vitro applications in 3 dimensions.

1. Santoro, F., Zhao, W., Joubert, L.-M., Duan, L., Schnitker, J., van de Burgt, Y., Lou, H.-Y., Liu, B., Salleo, A., Cui, L., Cui Y., Cui B., Revealing the Cell–Material Interface with Nanometer Resolution by Focused Ion Beam/Scanning Electron Microscopy. ACS Nano, 2017

2. Li X., Matino L., Zhang W., Klausen L., McGuire A., Lubrano C., Zhao W., Santoro F., Cui B., A nanostructure platform for live cell manipulation of membrane curvature, Nature Protocols, just accepted.

3. Iandolo D., Pennacchio F. A., Mollo V., Rossi D., Dannhauser D., Cui B., Owens R. M., Santoro F., Electron Microscopy for 3D Scaffolds–Cell Biointerface Characterization, Advanced Biosystems, 2018.

Francesca Santoro
Italian Institute of Technology
2:30 PM

To Patent or Publish or Both (Or Neither)


George Ligler
Department of Biomedical Engineering, UNC-Chapel Hill and NC State University
3:00 PM

Integrated biosensors

Speaker: Khaled N. Salama

3:30 PM

End of Day 3

6:30 PM

Award Ceremony, Closing Remarks, and Conference Dinner

By invitation only.

9:00 PM

Departure


Meet our Organizers

Sahika Inal

Organic Bioelectronics Laboratory

Jurgen Kosel

Sensing, Magnetism and Microsystems

Meet our Speakers

Pamela  Abshire

Department of Electrical and Computer Engineering, Institute for Systems Research, University of Maryland

Aziz Amine

Laboratory of Chemical Engineering and Environment, Faculty of Sciences and Techniques, Hassan II University of Casablanca, Morocco

Magnus  Berggren

Department of Science and Technology, Division of Physics and Electronics, Linköping University

Pai-Yen Chen

Department of Electrical and Computer Engineering, University of Illinois

Utkan  Demirci

Department of Electrical Engineering, Standford University

Ralph  Etienne-Cummings

Department of Electrical & Computer Engineering, Johns Hopkins University

Martin  Kaltenbrunner

Soft Matter Physics Department, Soft Electronics Laboratory, Johannes Kepler University

Sam  Kassegne

Department of Mechanical Engineering, San Diego State University

Niveen M. Khashab

Associate Professor, Physical Science and Engineering, KAUST

Guglielmo  Lanzani

Department of Physics, Politecnico di Milano

George Ligler

Department of Biomedical Engineering, UNC-Chapel Hill and NC State University

George  Malliaras

Electrical Engineering Division, University of Cambridge

Christian Nielsen

Materials Research Institute and School of Biological and Chemical Sciences, Queen Mary University of London

Jonathan  Rivnay

Department of Biomedical Engineering, Northwestern University

Frances  S. Ligler

Department of Biomedical Engineering, UNC-Chapel Hill and NC State University

Alberto Salleo

Department of Materials Science & Engineering, Stanford University

Francesca Santoro

Italian Institute of Technology

Mohamad Sawan

Center for Biomedical Research and Innovation, Westlake University, China

Sameer Sonkusale

Electrical and Computer Engineering, Tufts University

Natalie Stingelin

Functional Organic Materials, Georgia Institute of Technology