For more information visit: https://bese.kaust.edu.sa/study/bioengineering

Recent Submissions

  • Organic Bioelectronic Devices for Metabolite Sensing

    Koklu, Anil; Ohayon, David; Wustoni, Shofarul; Druet, Victor; Saleh, Abdulelah; Inal, Sahika (Chemical Reviews, American Chemical Society (ACS), 2021-10-05) [Article]
    Electrochemical detection of metabolites is essential for early diagnosis and continuous monitoring of a variety of health conditions. This review focuses on organic electronic material-based metabolite sensors and highlights their potential to tackle critical challenges associated with metabolite detection. We provide an overview of the distinct classes of organic electronic materials and biorecognition units used in metabolite sensors, explain the different detection strategies developed to date, and identify the advantages and drawbacks of each technology. We then benchmark state-of-the-art organic electronic metabolite sensors by categorizing them based on their application area (in vitro, body-interfaced, in vivo, and cell-interfaced). Finally, we share our perspective on using organic bioelectronic materials for metabolite sensing and address the current challenges for the devices and progress to come.
  • Inkjet-Printed In-Vitro Organic Electronic Devices

    Asghar, Hussain (2021-09) [Thesis]
    Advisor: Inal, Sahika
    Committee members: Baran, Derya; Salama, Khaled N.
    In-vitro electronic devices are promising to dynamically monitor minute-changes in biological systems. Electronic devices based on conducting polymers such as poly(3,4- ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) provide suitable and attractive substrates for biointerfacing. The soft polymer surface acts as a cushion for the living systems to interface while electronically detecting their properties. However, to this date, most bioelectronics devices have been fabricated via multi-step lithography techniques, which do not allow for mass fabrication and hence high throughput biosensing. Inkjet printing presents an alternative to fabricate organic bioelectronic devices. Besides being low-cost, inkjet printing allows to fabricate several devices in a short time with flexible design patterns and minimal material waste. Here, using inkjet printing, we fabricated PEDOT:PSS based organic electrochemical transistors (OECTs) for biomembrane interfacing. We optimized the deposition of various inks (silver nanoparticles (AgNPs), PEDOT:PSS, and the dielectric SU-8) used during the fabrication of these devices. We characterized the electrical characteristics of all-printed OECTs with various geometries and identified the high-performing ones. Due to the flexibility of ink optimization and design patterns, these all inkjet-printed electronic devices provide an alternative for mass production of biointerfacing platforms.
  • A Facile Magnetic System for Tracking of Medical Devices

    Swanepoel, Liam; Alsharif, Nouf; Przybysz, Alexander; Fourie, Pieter; Goussard, Pierre; Khan, Mohammad Asadullah; Almansouri, Abdullah S.; Kosel, Jürgen (Advanced Materials Technologies, Wiley, 2021-05-05) [Article]
    The largest disadvantage of modern day minimally invasive surgery is the required use of X-ray or fluoroscopic imaging for locating or tracking medical catheters and tubes. The implications are increased costs and effort, limited availability for instance in less developed countries, and the cumulative exposure to contrast dyes and ionizing radiation are detrimental to health, especially in young patients and neonates with increased sensitivity. In order to reduce the use of X-ray imaging and provide a wider accessibility, a facile magnetic system is proposed for subcutaneous medical device localization. It consists of a lightweight and flexible, biocompatible, and permanent magnet at the tip of the subcutaneous device and a sensing device to scan the dermal surface and locate the magnetic tip. The mechanical and magnetic properties of the magnetic tip are tailored to fit the requirements of the delicate catheter application. Evaluation of the tracking system using a 5 Fr magnetic tip resulted in a depth-dependent position and orientation error of 0.75 mm and 3.7°. Additionally, a maximum placement depth error of 0.96 mm is achieved. Evaluation of the system in vivo revealed its practicality and accuracy as well as the influence of potential user errors.
  • Frequency-modulation Stimulated Raman Scattering microscopy with an Acousto-Optic Tunable Filter

    Grassi, Elisa (2021-04) [Thesis]
    Advisor: Liberale, Carlo
    Committee members: Habuchi, Satoshi; Hauser, Charlotte
    Stimulated Raman Scattering (SRS) is a Coherent Raman microscopy method that has been increasingly employed in recent years for highly-specific, label-free, and high-speed bioimaging. Compared to a similar Coherent Raman method, the so-called Coherent Anti-Stokes Scattering (CARS) microscopy, it exhibits advantages such as the absence of nonresonant background (NRB) and the linearity of the signal intensity on the concentration of molecules of interest. However, SRS can be affected by unwanted background signals that hinder the acquisition of an accurate Raman information. These unwanted signals are generated by parasitic effects that are difficult to suppress in standard SRS setups. Here, I present a frequency-modulation (FM) SRS technique via an Acousto-Optic Tunable ioilter (AOTF), describing its implementation on Vibra Lab setup and assessing its efficiency with imaging results. The FM technique provides a cancellation of the unwanted background signals, maintaining intact the SRS information. It is based on the weak spectral dependence of the parasitic effects as compared to the high spectral specificity of the SRS signal. The proposed scheme presents a few advantages when compared with other solutions presented in the literature. In particular, it doesn't require a complex setup configuration, and it can be used seamlessly in a very broad range of the vibrational spectrum.
  • Mixed Conduction in an N-Type Organic Semiconductor in the Absence of Hydrophilic Side-Chains

    Surgailis, Jokubas; Savva, Achilleas; Druet, Victor; Paulsen, Bryan D.; Wu, Ruiheng; Hamidi-Sakr, Amer; Ohayon, David; Nikiforidis, Georgios; Chen, Xingxing; McCulloch, Iain; Rivnay, Jonathan; Inal, Sahika (Advanced Functional Materials, Wiley, 2021-03-18) [Article]
    Organic electrochemical transistors (OECTs) are the building blocks of biosensors, neuromorphic devices, and complementary circuits. One rule in the materials design for OECTs is the inclusion of a hydrophilic component in the chemical structure to enable ion transport in the film. Here, it is shown that the ladder-type, side-chain free polymer poly(benzimidazobenzophenanthroline) (BBL) performs significantly better in OECTs than the donor–acceptor type copolymer bearing hydrophilic ethylene glycol side chains (P-90). A combination of electrochemical techniques reveals that BBL exhibits a more efficient ion-to-electron coupling and higher OECT mobility than P-90. In situ atomic force microscopy scans evidence that BBL, which swells negligibly in electrolytes, undergoes a drastic and permanent change in morphology upon electrochemical doping. In contrast, P-90 substantially swells when immersed in electrolytes and shows moderate morphology changes induced by dopant ions. Ex situ grazing incidence wide-angle X-ray scattering suggests that the particular packing of BBL crystallites is minimally affected after doping, in contrast to P-90. BBL's ability to show exceptional mixed transport is due to the crystallites’ connectivity, which resists water uptake. This side chain-free route for the design of mixed conductors could bring the n-type OECT performance closer to the bar set by their p-type counterparts.
  • Flexible Hall sensor made of laser-scribed graphene

    Kaidarova, Altynay; Liu, Wenhao; Swanepoel, Liam; Almansouri, Abdullah S.; Geraldi, Nathan; Duarte, Carlos M.; Kosel, Jürgen (npj Flexible Electronics, Springer Nature, 2021-02-15) [Article]
    Graphene has shown considerable potential for sensing magnetic fields based on the Hall Effect, due to its high carrier mobility, low sheet carrier density, and low-temperature dependence. However, the cost of graphene in comparison to conventional materials has meant that its uptake in electronic manufacturing has been slow. To lower technological barriers and bring more widespread adoption of graphene Hall sensors, we are using a one-step laser scribing process that does not rely on multiple steps, toxic chemicals, and subsequent treatments. Laser-scribed graphene Hall sensors offer a linear response to magnetic fields with a normalized sensitivity of ~1.12 V/AT. They also exhibit a low constant noise voltage floor of ~ 50 nV/Hz−−−√ for a bias current of 100 µA at room temperature, which is comparable with state-of-the-art low-noise Hall sensors. The sensors combine a high bendability, come with high robustness and operating temperatures up to 400 °C. They enable device ideas in various areas, for instance, soft robotics. As an example, we combined a laser-scribed graphene sensor with a deformable elastomer and flexible magnet to realize low-cost, compliant, and customizable tactile sensors.
  • MXene improves the stability and electrochemical performance of electropolymerized PEDOT films

    Wustoni, Shofarul; Saleh, Abdulelah; El Demellawi, Jehad K.; Koklu, Anil; Hama, Adel; Druet, Victor; Wehbe, Nimer; Zhang, Yi Zhou; Inal, Sahika (APL Materials, AIP Publishing, 2020-12-01) [Article]
    Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(styrene sulfonate) (PSS) is the most commonly used conducting polymer in organic bioelectronics. However, electrochemical capacitances exceeding the current state-of-the-art are required for enhanced transduction and stimulation of biological signals. The long-term stability of conducting polymer films during device operation and storage in aqueous environments remains a challenge for routine applications. In this work, we electrochemically synthesize a PEDOT composite comprising the water dispersible two-dimensional conducting material Ti3C2 MXene. We find that incorporating MXene as a co-dopant along with PSS leads to PEDOT:PSS:MXene films with remarkably high volumetric capacitance (607.0 ± 85.3 F cm−3) and stability (capacity retention = 78.44% ± 1.75% over 500 cycles), outperforming single dopant-comprising PEDOT films, i.e., PEDOT:PSS and PEDOT:MXene electropolymerized under the same conditions on identical surfaces. The stability of microfabricated PEDOT:PSS:MXene electrodes is evaluated under different conditions, i.e., when the films are exposed to sonication (∼100% retention over 6 min), upon immersion in cell culture media for 14 days (∆|Z| = 2.13%), as well as after continuous electrical stimulation. Furthermore, we demonstrate the use of a PEDOT:PSS:MXene electrode as an electrochemical sensor for sensitive detection of dopamine (DA). The sensor exhibited an enhanced electrocatalytic activity toward DA in a linear range from 1 μM to 100 μM validated in mixtures containing common interferents such as ascorbic acid and uric acid. PEDOT:PSS:MXene composite is easily formed on conductive substrates with various geometries and can serve as a high performance conducting interface for chronic biochemical sensing or stimulation applications.
  • VLG-Net: Video-Language Graph Matching Network for Video Grounding

    Qu, Sisi; Soldan, Mattia; Xu, Mengmeng; Tegner, Jesper; Ghanem, Bernard (arXiv, 2020-11-19) [Preprint]
    Grounding language queries in videos aims at identifying the time interval (or moment) semantically relevant to a language query. The solution to this challenging task demands the understanding of videos' and queries' semantic content and the fine-grained reasoning about their multi-modal interactions. Our key idea is to recast this challenge into an algorithmic graph matching problem. Fueled by recent advances in Graph Neural Networks, we propose to leverage Graph Convolutional Networks to model video and textual information as well as their semantic alignment. To enable the mutual exchange of information across the domains, we design a novel Video-Language Graph Matching Network (VLG-Net) to match video and query graphs. Core ingredients include representation graphs, built on top of video snippets and query tokens separately, which are used for modeling the intra-modality relationships. A Graph Matching layer is adopted for cross-modal context modeling and multi-modal fusion. Finally, moment candidates are created using masked moment attention pooling by fusing the moment's enriched snippet features. We demonstrate superior performance over state-of-the-art grounding methods on three widely used datasets for temporal localization of moments in videos with natural language queries: ActivityNet-Captions, TACoS, and DiDeMo.
  • Cancer Therapy based on Core-Shell Iron-Iron Oxide Nanowires

    Martinez Banderas, Aldo (2020-11) [Dissertation]
    Advisor: Kosel, Jürgen
    Committee members: Merzaban, Jasmeen; Ooi, Boon S.; Wilhelm, Claire
    Nanomaterials have been widely investigated for improving the treatment of diseases acting as vectors for diverse therapies and as diagnostic tools. Iron-based nanowires possess promising potential for biomedical applications due to their outstanding properties. The combination of different therapeutic and diagnostic strategies into one single platform is an approach for more efficient and safer treatments. In this thesis, I investigate the application of iron-iron oxide core-shell nanowires as therapeutic agents for cancer treatment. In particular, a novel method for multimodal cancer cell destruction was developed combining the optical, magneto-mechanical and chemotherapeutic properties of functionalized nanowires. By functionalizing the nanowires with doxorubicin through a pH-sensitive linker, the first treatment modality was achieved by selective intracellular drug release. The second treatment modality utilizes the mechanical disturbance exerted by the nanowires upon the application of a low-power alternating magnetic field. The third treatment modality exploits the capability of the nanowires to transform optical energy, absorbed from near-infrared irradiation, into heat. The efficiency of the three treatment modalities both independently and combined were tested in breast cancer cells with near complete cell death (90%). The combination of the different strategies can potentially reduce side effects and treatment time. Additionally, I studied the potential of these iron-iron oxide core-shell nanowires as diagnostic tools, included in the Appendix of this dissertation. Specifically, I studied their capability to act as magnetic resonance imaging contrast agents for cell labeling, detection and tracking. Therein, a high performance as T2 contrast agents was confirmed evaluating the effect of oxidation and surface coatings on the T2 contrast in the tailored transverse relaxivities. The detection of nanowire-labeled cancer cells was demonstrated in T2-weighted images of cells implanted in tissue-mimicking phantoms and in mouse brain. Labeling the cells with nanowires enabled high-resolution cell detection after in vivo implantation (~10 cells) over a minimum of 40 days. The capability of these magnetic nanowires of being remotely controllable and detectable make them an attractive option in the treatment and diagnosis of cancer and in cell therapy. Future directions include preclinical studies for testing the nanowire-based photothermal therapy for tumor ablation.
  • Inkjet-printed Ti3C2Tx MXene electrodes for multimodal cutaneous biosensing

    Saleh, Abdulelah; Wustoni, Shofarul; Bihar, Eloise; El Demellawi, Jehad K.; Zhang, Yizhou; Hama, Adel; Druet, Victor; Yudhanto, Arief; Lubineau, Gilles; Alshareef, Husam N.; Inal, Sahika (Journal of Physics: Materials, IOP Publishing, 2020-10-16) [Article]
    Among the existing 2D materials, MXenes, i.e., transition metal carbides, nitrides and/or carbonitrides, stand out for their excellent electrochemical properties. On account of their high charge storage capacity, metal-like conductivity, biocompatibility as well as hydrophilicity, Ti3C2Tx MXene-based inks hold great potential for scalable production of skin conformable electronics via direct printing methods. Herein, we develop an aqueous MXene ink and inkjet-print MXene films on freestanding, flexible conducting polymer-based substrates. These skin-adherent MXene electrodes detect electrocardiography signals with high signal-to-noise ratio while exhibiting preserved electrical performance after 1000 cycles of bending with a 50 day-long shelf life in ambient conditions. We show that printed MXene films can further be functionalized to perform as multifunctional biosensing units. When integrated with a sodium (Na+) ion-selective membrane, MXene electrodes detect Na+ in artificial sweat with a sensitivity of 40 mV per decade. When the films are functionalized with antibodies, they generate an electrical signal in response to a pro-inflammatory cytokine protein (interferon gamma) with a sensitivity of 3.9 mV per decade. Our findings demonstrate how inkjet-printed MXene films simplify the fabrication of next-generation wearable electronic platforms that comprise multimodal sensors.
  • Benchmarking the Performance of Electropolymerized Poly(3,4-ethylenedioxythiophene) Electrodes for Neural Interfacing

    Nikiforidis, Georgios; Wustoni, Shofarul; Routier, Cyril; Hama, Adel; Koklu, Anil; Saleh, Abdulelah; Steiner, Nadia; Druet, Victor; Fiumelli, Hubert; Inal, Sahika (Macromolecular Bioscience, Wiley, 2020-08-20) [Article]
    The development of electronics adept at interfacing with the nervous system is an ever-growing effort, leading to discoveries in fundamental neuroscience applied in clinical setting. Highly capacitive and electrochemically stable electronic materials are paramount for these advances. A systematic study is presented where copolymers based on 3,4-ethylenedioxythiophene (EDOT) and its hydroxyl-terminated counterpart (EDOTOH) are electropolymerized in an aqueous solution in the presence of various counter anions and additives. Amongst the conducting materials developed, the copolymer p(EDOT-ran-EDOTOH) doped with perchlorate in the presence of ethylene glycol shows high specific capacitance (105 F g-1 ), and capacitance retention (85%) over 1000 galvanostatic charge-discharge cycles. A microelectrode array-based on this material is fabricated and primary cortical neurons are cultured therein for several days. The microelectrodes electrically stimulate targeted neuronal networks and record their activity with high signal-to-noise ratio. The stability of charge injection capacity of the material is validated via long-term pulsing experiments. While providing insights on the effect of additives and dopants on the electrochemical performance and operational stability of electropolymerized conducting polymers, this study highlights the importance of high capacitance accompanied with stability to achieve high performance electrodes for biological interfacing.
  • A Self-standing Organic Supercapacitor to Power Bioelectronic Devices

    Nikiforidis, Georgios; Wustoni, Shofarul; ohayon, David; Druet, Victor; Inal, Sahika (ACS Applied Energy Materials, American Chemical Society (ACS), 2020-07-27) [Article]
    The last decade has witnessed rapid progress in the development of implantable and wearable bio(chemical) sensors, which allow for real-time, continuous health monitoring. Among different device configurations, organic electrochemical transistors (OECTs) have shown great potential in transducing weak biological signals with on-site amplification and as components of complex circuits with low power requirements. Yet, a significant technological challenge remains in the way these devices are integrated with power sources that are conventionally bulky and rigid. Here, we present a simple process to assemble a supercapacitor (SC) that is self-standing, lightweight, and biocompatible and made of two identical conducting polymer (poly(3,4-ethylenedioxythiophene) electrodes and an agarose hydrogel comprising alkali metal halides. This SC is distinguished by its high energy and power density (20 Wh kg-1 and 105 W kg-1, respectively), moderate gravimetric specific capacitance (70 F g-1), excellent stability (charge retention of 75% after 12,000 cycles), operational flexibility (can accommodate various types of aqueous electrolytes), long-lasting self-discharge (>10 h), and fast response time (between 0.1 and 30 s). We use the SC to power a micron-scale OECT, which selectively detects sodium ions in aqueous media. When miniaturized, the SC maintains its high performance and delivers a volumetric capacitance of 240 F cm-3, highlighting the possibility of fabrication in nonstandard form factors to couple with various bioelectronic devices. This low-cost and portable power source instigates the development of robust and biocompatible onboard power sources to be implemented alongside biosensors.
  • Learning Heat Diffusion for Network Alignment

    Qu, Sisi; Xu, Mengmeng; Ghanem, Bernard; Tegner, Jesper (arXiv, 2020-07-10) [Preprint]
    Networks are abundant in the life sciences. Outstanding challenges include how to characterize similarities between networks, and in extension how to integrate information across networks. Yet, network alignment remains a core algorithmic problem. Here, we present a novel learning algorithm called evolutionary heat diffusion-based network alignment (EDNA) to address this challenge. EDNA uses the diffusion signal as a proxy for computing node similarities between networks. Comparing EDNA with state-of-the-art algorithms on a popular protein-protein interaction network dataset, using four different evaluation metrics, we achieve (i) the most accurate alignments, (ii) increased robustness against noise, and (iii) superior scaling capacity. The EDNA algorithm is versatile in that other available network alignments/embeddings can be used as an initial baseline alignment, and then EDNA works as a wrapper around them by running the evolutionary diffusion on top of them. In conclusion, EDNA outperforms state-of-the-art methods for network alignment, thus setting the stage for large-scale comparison and integration of networks.
  • A Computational Analysis of Cell Fate Dynamics during Zebrafish Embryonic Development using Single Cell Transcriptomics

    Balubaid, Ali (2020-07) [Thesis]
    Advisor: Tegner, Jesper
    Committee members: Li, Mo; Gao, Xin
    Development and the associated cellular differentiation are some of the most fundamental processes in biology. Since the early conception of the Waddington landscape, with cells portrayed as rolling down a landscape, understanding these processes has been at the forefront of biology. Progress in tissue regeneration, organoid culture, and cellular reprogramming relies on our ability to unfold cellular decision making and its dynamics. In this thesis, we ask to what extent development follows such landscape. Secondly, we address whether cellular branching points are discrete events. Given the recent surge in single-cell genomics data, we can now address these fundamental questions. To this end, we analyzed two large-scale single-cell RNAseq time course datasets from vertebrate embryogenesis in zebrafish. From the Waddington analogy, we expect the cell-to-cell correlation to increase across development as cells specialize. Our analysis does not show a linear trend, but rather, that cell-to-cell variability is lowest during gastrulation. Interestingly, the two different datasets from two different laboratories display a qualitatively similar trend, providing internal consistency of our analysis. To uncover the branchpoint dynamics, we extended our analysis to include computations of gene-to-gene correlations. It has been shown, using PCR data, that the transition index, the ratio between cell-to-cell and gene-to-gene correlations, displays a peak during such branchpoints, suggesting discrete transitions. To this end, we tracked individual developmental trajectories, and characterized both correlations, enabling computation of the transition index. However, the cell-to-cell correlation and gene-to-gene correlation did not follow a generic inverse relationship, as previously suggested. No unique signal corresponding to the branchpoints could, thus, be detected. Therefore, our analysis does not support the view that branchpoints during vertebrate embryogenesis are discrete, well-defined transition events. In conclusion, this first large-scale single-cell based analysis of time-resolved developmental data does not support a downhill rolling ball notion where cells decide their fate at discrete transition points. The temporal organization of an undulating developmental landscape appears to be more complex than initially conceptualized by Waddington. Therefore, it is of paramount interest to extend this type of analysis to other systems and to develop techniques to compute such landscape in a data-driven manner.
  • A Triaxial Flexible Magnetic Tunnel Junction Sensor for Catheter Tracking

    Mashraei, Yousof; Swanepoel, Liam; Kosel, Jürgen (Institute of Electrical and Electronics Engineers (IEEE), 2020-01-15) [Conference Paper]
    A cardiac catheterization procedure is a minimally-invasive surgery, which is employed in case of various cardiovascular conditions and requires a high precision. The method relies heavily on x-ray imaging and contrast dyes to guide the catheter inside the blood vessels, posing risks to patients and the medical staff. Thus, a miniaturized tri-axes magnetic sensor is developed for orientation monitoring using the Earth’s magnetic field, to assist the guiding of the catheter. The magnetic sensors are realized by flexible magnetic tunnel junctions on ultra-thin silicon substrate, ensuring a high sensitivity to magnetic fields. These flexible sensors have a bending endurance of over 1000 cycles without signs of fatigue. Three sensors are mounted on the tip of a catheter, implementing a sensor-on-tube concept for orthogonal 3-axes measurements. The sensors have an MR ratio of 29% and a high sensitivity of about 9 Ω/°. With a weight of only 16 μg and a thickness of 4 μm, each sensor adds a negligible weight and increase in size, making them attractive for applications, where extreme miniaturization is sought. The flexible tri-axes MTJ is mounted onto the tip of a cardiac catheter with 3 mm in diameter.
  • A Self-Powered Magneto-Acoustic Tracking Transducer

    Almansouri, Abdullah S.; Swanepoel, Liam; Salama, Khaled N.; Kosel, Jürgen (Institute of Electrical and Electronics Engineers (IEEE), 2020-01-15) [Conference Paper]
    Acoustic telemetry is widely used for many tracking applications. Objects or subjects are tracked by attaching an acoustic transmitter onto them or having them wear them. The acoustic signal is then detected by different microphones to determine the location of the tagged target. The size and the weight of the tag determine the size of the target that can be tracked. In the case of small-sized tags, about 80% of the volume is consumed by the battery and electronics, while less than 20% by the actual acoustic transducer. Here, we propose a self-powered acoustic tracking transducer that utilizes a magnetic frequency up-converter that directly converts the low-frequency motions of a target to a high-frequency acoustic signal. The intensity of the output signal is enhanced by realizing a bistable cantilever design by local crystallization of an amorphous metal transducer. A micro device has been realized with dimensions of 8×13×38 mm3 and a weight of 1.3 g. The measurement results show that the transducer up-converts a low-frequency of 7 Hz to 15 kHz, directly and without the need for an external power source.
  • Supramolecular biopolymers for tissue engineering

    Perez Pedroza, Rosario; Ávila-Ramírez, Alan; Khan, Zainab; Moretti, Manola; Hauser, Charlotte (Accepted by Advances in Polymer Technology, Hindawi Limited, 2020) [Article]