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

Recent Submissions

  • Continuous extraction and concentration of secreted metabolites from engineered microbes using membrane technology

    Overmans, Sebastian; Ignacz, Gergo; Beke, Aron K.; Xu, Jiajie; Saikaly, Pascal; Szekely, Gyorgy; Lauersen, Kyle J. (Green Chemistry, Royal Society of Chemistry (RSC), 2022-05-18) [Article]
    Microalgal cultivation in photobioreactors and membrane separations are both considered sustainable processes. Here we explore their synergistic combination to extract and concentrate a heterologous sesquiterpenoid produced by engineered green algal cells. A hydrophobic hollow-fiber membrane contactor was used to allow interaction of culture broth and cells with a dodecane solvent phase to accumulate algal produced patchoulol. Subsequent continuous membrane extraction of patchoulol from dodecane enabled product concentration in a methanol stream as well as dodecane recovery for its reuse. A structure-based prediction using machine learning was used to model a process whereby 100% patchoulol recovery from dodecane could be achieved with solvent-resistant nanofiltration membranes. Solvent consumption, E-factor, and economic sustainability were assessed and compared with existing patchoulol production processes. Our extraction and product purification process offers six- and two-orders of magnitude lower solvent consumption compared to synthetic production and thermal-based separation, respectively. Our proposed methodology is transferable to other microbial systems for the isolation of high-value isoprenoid and hydrocarbon products.
  • A comparison of solvents for their suitability as solvent-culture two phase systems for living extraction of microbial isoprenoids using the green microalga Chlamydomonas reinhardtii as a model organism

    AlKaff, Salma (2022-05-14) [Thesis]
    Advisor: Lauersen, Kyle J.
    Committee members: Saikaly, Pascal; Szekely, Gyorgy
    Biotechnology and metabolic engineering of microbes has become a mature technology in many host microorganisms. A key method for the capture and quantification of heterologous and natural microbially produced isoprenoid products is to incubate growing cultures with a bio-compatible solvent. This is a culture-solvent two phase system that allows the continuous extraction, or ‘milking’, of hydrophobic products produced from microbial hosts. Solvent milking systems are highly valuable because they allow capture and subsequent analytics to be performed in a relatively straightforward manner. However, the currently used solvents are petroleum-derived, or can be challenging to work with at scale. Therefore, this thesis sought to investigate the biocompatibility of alternative solvents, including some examples of “green solvents” derived from biomass sources, using a model microalga as a study organism that had been previously engineered to produce the heterologous sesquiterpenoid patchoulol. In total 22 solvents were investigated, their 50% lethal concentration (LC50) determined, and their abilities to accumulate patchoulol from the algal culture compared. Solvents that were not-immediately lethal to algal cells and accumulated patchoulol, were also tested for their capacities for further isolation of patchoulol out of the solvent, either in ethanol, methanol, or through solid phase extraction. This work provides a broad foundation of information which is important for future efforts at microbial product milking and solvent choices for bio-process designs, especially with engineered microalgae.
  • Combinatorial Engineering Enables Photoautotrophic Growth in High Cell Density Phosphite-Buffered Media to Support Engineered Chlamydomonas reinhardtii Bio-Production Concepts

    Abdallah, Malak N.; Wellman, Gordon B.; Overmans, Sebastian; Lauersen, Kyle J. (Frontiers in Microbiology, Frontiers Media SA, 2022-05-13) [Article]
    Chlamydomonas reinhardtii has emerged as a powerful green cell factory for metabolic engineering of sustainable products created from the photosynthetic lifestyle of this microalga. Advances in nuclear genome modification and transgene expression are allowing robust engineering strategies to be demonstrated in this host. However, commonly used lab strains are not equipped with features to enable their broader implementation in non-sterile conditions and high-cell density concepts. Here, we used combinatorial chloroplast and nuclear genome engineering to augment the metabolism of the C. reinhardtii strain UVM4 with publicly available genetic tools to enable the use of inorganic phosphite and nitrate as sole sources of phosphorous and nitrogen, respectively. We present recipes to create phosphite-buffered media solutions that enable high cell density algal cultivation. We then combined previously reported engineering strategies to produce the heterologous sesquiterpenoid patchoulol to high titers from our engineered green cell factories and show these products are possible to produce in non-sterile conditions. Our work presents a straightforward means to generate C. reinhardtii strains for broader application in bio-processes for the sustainable generation of products from green microalgae.
  • Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation

    Ye, Jin; Calvo, Isabel A; Cenzano, Itziar; Vilas, Amaia; Martinez-de-Morentin, Xabier; Lasaga, Miren; Alignani, Diego; Paiva, Bruno; Viñado, Ana C; San Martin-Uriz, Patxi; Romero, Juan P; Quilez Agreda, Delia; Miñana Barrios, Marta; Sancho-González, Ignacio; Todisco, Gabriele; Malcovati, Luca; Planell, Nuria; Saez, Borja; Tegner, Jesper N; Prosper, Felipe; Gomez-Cabrero, David (iScience, Elsevier BV, 2022-04-22) [Article]
    Understanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the first time 14 intermediate cell states and 11 stages of differentiation in the endothelial and mesenchymal BM compartments, respectively. Our data provide the most comprehensive description to date of the murine HSC-regulatory microenvironment and suggest a higher level of specialization of the cellular circuits than previously anticipated. Furthermore, this deep characterization allows inferring conserved features in human, suggesting that the layers of microenvironmental regulation of hematopoiesis may also be shared between species. Our resource and methodology is a stepping-stone toward a comprehensive cell atlas of the BM microenvironment.
  • Rare variant analysis on UK Biobank

    Liu, Yang (2022-04-17) [Thesis]
    Advisor: Hoehndorf, Robert
    Committee members: Hauser, Charlotte; Gojobori, Takashi
    Genome-wide Association Studies (GWAS) is the study used to associate common variants and phenotypes and has uncovered thousands of disease-associated variants. However, there is limited research on the contribution of a rare variant. The UK Biobank (UKB) contains detailed medical records and genetic information for nearly 500,000 individuals and offers a great opportunity for genetic association studies on rare variants. Here we focused on the role of rare protein-coding variants on UKB phenotypes. We selected three diseases for analysis: breast cancer, hypothyroidism and type II diabetes. We defined criteria for qualifying variants and pruned the control group to reduce interference signals from similar phenotypes. We identified the most known biomarkers for those diseases, such as BRCA1 and BRCA2 gene for breast cancer, TG and TSHR gene for hypothyroidism and GCK for type II diabetes. This result supports the model validity and clarifies the contribution of rare variants to diseases. Moreover, we also tried the geneset based collapsing method to aggregate information across genes to strengthen the signal from rare variants and build a diagnosis model that only relies on the genetic information. Our model could achieve great performance with an AUC of more than 20% improvement for type II diabetes and breast cancer and more than 90% accuracy for hypothyroidism.
  • Investigation of heterologous expression of the non-ribosomal peptide blue pigment synthase and its activator from the nuclear genome of the model microalga Chlamydomonas reinhardtii

    Shlbi, Manar (2022-03-31) [Thesis]
    Advisor: Lauersen, Kyle J.
    Committee members: Grunberg, Raik; Saikaly, Pascal
    The non-ribosomal peptide synthase (NRPS) blue pigment synthase (BpsA) has been shown in several heterologous hosts to mediate the production of the blue pigment indigoidine from two molecules of L-glutamine. Activation of BpsA is mediated by transfer of a coenzyme A (CoA) by a 4′-phosphopantetheinyl transferase (4′-PPTase). In this thesis, I explored heterologous co-expression of BpsA and the Pseudomonas aeruginosa 4′-PPTase (PaPcpS) and their co- localization to either cytoplasm or chloroplast stroma of the green model microalga Chlamydomonas reinhardtii. The alga represents a potentially sustainable production host for indigoidine, as it is able to grow using CO2 as a sole carbon source and (sun)light for its energy. Both heterologous proteins (BpsA and PaPcpS) could be expressed as full-length fusion proteins with either the mVenus yellow fluorescent reporter or spectinomycin resistance (aadA) selection marker in both subcellular localisations. Dual transformants were identified and subjected to multiple growth conditions to determine whether indigoidine was produced. Under no condition tested was indigoidine detected, indicating that either activation of BpsA or the catalysis of L-glutamine to indigoidine was not occurring in alga. Future work will be required to determine whether it is possible to activate the BpsA in C. reinhardtii. However, this represents the first documented example of expression of a heterologous NRPS in a eukaryotic alga and may serve as foundational work for other target NRPS expression projects.
  • MXene supported Iron single-atom catalyst for bio sensing applications

    Shetty, Saptami (2022-03-28) [Thesis]
    Advisor: Salama, Khaled N.
    Committee members: Lauersen, Kyle J.; Tung, Vincent
    The adrenal medulla is the inner part of adrenal glands located above each kidney, that produces catecholamines. Neuroblastoma and pheochromocytoma are the most prevalent malignancies of the adrenal medulla. Quantitative diagnosis of urinary catecholamines using HPLC-coupled Mass detectors is the current method for the diagnosis of neuroblastoma and pheochromocytoma. There are two major problems with this approach, (i) Because the catecholamines concentrations have short half-life (10-100 s), a series of urine tests must be performed throughout 24hr, detecting each catecholamine separately, is inconvenient and time-consuming; (ii) mass detectors are expensive, bulky, and require highly skilled personal. Vanillylmandelic (VMA), and homavanillic acid (HVA) are the by-products of catecholamines and are emerging alternative biomarker for catecholamines due to their high stability. Here, we developed a rapid, sensitive, miniaturized, and cheaper sensing platform for simultaneous quantifications of dopamine (DA), VMA, and HVA, with the aid of iron single-atom catalysts (Fe-SACs), based electrochemical sensor. SACs are atomically distributed metal atoms that have a maximum atomic utility rate of nearly 100%, compared to 30% for traditional metal nanoparticles. MXene sheets are employed to stabilize Fe-SACs, where, the exposed lone pairs of MXene serve as sites covalently linking high-energy single Fe atoms. MXene/Fe-SACs were synthesized by treating Ti3C2TxMXene with Iron chloride via freeze-drying followed by annealing. The successful formation of the material was verified by state-of-the-art characterizations. The MXene/Fe-SACs show superior electrocatalytic performance to the commonly used Fe- nanomaterials. Then, it was coated on the electrode surface and used to analyze DA, VMA, and HVA simultaneously via cyclic voltammetry (CV) and square-wave voltammetry (SWV). Under optimized conditions, the MXene/Fe-SACs electrochemical sensor showed detection limits as low as 1 nM and a linear range between 1 nM-100 μM for DA, LOD of 5 nM & linear range of 10 nM-100 μM VMA, and LOD of 10 nM & linear range of 20 nM-100 μM HAV. The method proved successful in detecting biomarkers in (spiked) synthetic urine and human serum. Furthermore, the method was successfully demonstrated in the determination of DA release from PC12 live cells, suggesting the wide practical use of SACs in sensing catecholamines-related metabolites.
  • Characterizing the Chemical Contaminants Diversity and Toxic Potential of Untreated Wastewater From a Drug Rehabilitation Hospital: Understanding Impact on Downstream Environment

    Baasher, Fras; Wang, Tian-Nyu; Zulhelmi Bin Yusnan, Muhammad; Alkahtani, Mohsen; Bashawri, Yasir M.; Al Qarni, Hamed; Hong, Pei-Ying (FRONTIERS IN ENVIRONMENTAL SCIENCE, Frontiers Media SA, 2022-03-24) [Article]
    This study characterizes a total of 21 wastewater samples collected from Al Amal hospital, and aims to determine if untreated hospital wastewater may impose a potentially detrimental impact on the downstream municipal biological wastewater treatment process. By means of solid phase extraction and liquid chromatography with tandem mass spectrometry (LC-MS/MS), chemical contaminants in these wastewater samples were determined in a non-targeted manner. In-silico characterization for the mutagenicity and reactive oxygen species (ROS) producing capabilities was performed by checking against database and literature. However, majority of the chemical contaminants have no prior information available and remain uncharacterized for both traits. Instead, in-vitro mutagenicity tests by means of Ames test showed that majority of the samples were non-mutagenic except for 5 samples that imposed mutagenic effect at high concentrations of >×10. In-vitro tests to determine for intracellular ROS production further showed that one of the mutagenic samples collected on Jun-22 positively induce ROS production and subsequently increased horizontal gene transfer via natural transformation. The findings in this study suggest that a specialty hospital like Al Amal does not frequently contribute mutagenic compounds and ROS to the wastewater streams, and in instances where it contributed positively, would require a high concentration to do so. Hence in general, wastewater streams from a specialty hospital like Al Amal may be unlikely to significantly perturb the downstream environment.
  • Combinatorial engineering for photoautotrophic production of recombinant products from the green microalga Chlamydomonas reinhardtii

    Abdallah, Malak N.; Wellman, Gordon B.; Overmans, Sebastian; Lauersen, Kyle J. (Cold Spring Harbor Laboratory, 2022-03-01) [Preprint]
    Chlamydomonas reinhardtii has emerged as a powerful green cell factory for metabolic engineering of sustainable products created from the photosynthetic lifestyle of this microalga. Advances in nuclear genome and transgene expression engineering are allowing robust engineering strategies to be demonstrated in this host. However, commonly used lab strains are not equipped with features to enable their broader implementation in non-sterile conditions and high-cell density concepts. Here, we use combinatorial chloroplast and nuclear genome engineering to complement the C. reinhardtii strain UVM4 with publicly available genetic tools to enable the use of inorganic phosphite and nitrate as a sole the source phosphorous and nitrogen, respectively. We present recipes to create phosphite-buffered media solutions that enable high cell density algal cultivation. We then combine previously reported engineering strategies to produce the heterologous sesquiterpenoid patchoulol to high titers from our engineered green cell factories and show these products are possible to produce in under non-sterile conditions. Our work presents a straightforward means to generate C. reinhardtii strains for broader application in bio-processes for the sustainable generation of products.
  • Operation mechanism of n-type organic electronic metabolite sensors

    Druet, Victor; Nayak, Prem; Ohayon, David; Koklu, Anil; Inal, Sahika; Chen, Xingxing; Moser, Maximilian; McCulloch, Iain (Fundació Scito, 2022-02-07) [Presentations]
    When combined with oxidase enzymes, the NDI-T2 based electron transporting (n-type) polymer led to high performance metabolite sensors, yet their working mechanism has been poorly understood.[1], [2] By monitoring oxygen, hydrogen peroxide, and pH changes in the electrolyte surrounding the n-type channel and gate as well as the potential of each electrical contact in the transistor, we shed light on the catalytic events occurring at the polymer-enzyme interface. We show that in its doped sate, the n-type film performs oxygen reduction reaction and that the n-OECT characteristics are sensitive to oxygen. We find a correlation between the amount of dissolved oxygen and the n-OECT sensor current generated during the metabolite oxidation and that using the n-type polymer at the gate electrode is critical for sensor operation. Our results show the importance of in operando analysis for understanding polymer-catalytic enzyme activity, as well as the importance of ambient oxygen in the operation of n-type devices.
  • 14 GHz Schottky Diodes using a p -Doped Organic Polymer

    Loganathan, Kalaivanan; Scaccabarozzi, Alberto D.; Faber, Hendrik; Ferrari, Federico; Bizak, Zhanibek; Yengel, Emre; Naphade, Dipti R.; Gedda, Murali; He, Qiao; Solomeshch, Olga; Adilbekova, Begimai; Yarali, Emre; Tsetseris, Leonidas; Salama, Khaled N.; Heeney, Martin; Tessler, Nir; Anthopoulos, Thomas D. (Advanced Materials, Wiley, 2022-01-06) [Article]
    The low carrier mobility of organic semiconductors and the high parasitic resistance and capacitance often encountered in conventional organic Schottky diodes, hinder their deployment in emerging radio frequency (RF) electronics. Here we overcome these limitations by combining self-aligned asymmetric nanogap electrodes (∼25 nm) produced by adhesion-lithography, with a high mobility organic semiconductor and demonstrate RF Schottky diodes able to operate in the 5G frequency spectrum. We used C<sub>16</sub> IDT-BT, as the high hole mobility polymer, and studied the impact of p-doping on the diode performance. Pristine C<sub>16</sub> IDT-BT-based diodes exhibit maximum intrinsic and extrinsic cutoff frequencies (f<sub>C</sub> ) of >100 and 6 GHz, respectively. This extraordinary performance is attributed primarily to the planar nature of the nanogap channel and the diode's small junction capacitance (< 2 pF). Doping of C<sub>16</sub> IDT-BT with the molecular p-dopant C<sub>60</sub> F<sub>48</sub> , improves the diode's performance further by reducing the series resistance resulting to intrinsic and extrinsic f<sub>C</sub> of >100 and ∼14 GHz respectively, while the DC output voltage of a RF rectifier circuit increases by a tenfold. Our work highlights the importance of the planar nanogap architecture and paves the way for the use of organic Schottky diodes in large-area radio frequency electronics of the future. This article is protected by copyright. All rights reserved.
  • Effects of Pharmacotherapy, Neurodevelopment, Sex and Structural Asymmetry on Regional Intrinsic Homotopic Connectivity in Youths with Attention Deficit Hyperactivity Disorder.

    Homoud, Zainab (2021-12) [Thesis]
    Advisor: Ombao, Hernando
    Committee members: Hauser, Charlotte; Al-Naffouri, Tareq Y.
    Functional magnetic resonance imaging studies have long demonstrated a high degree of correlated activity between the left and right hemispheres of the brain. Interregional correlations between the time series of each brain voxel or region and its homotopic pair have recently been identified by methods such as homotopic resting-state functional connectivity (H-RSFC). However, little is known about whether interhemispheric regions in patients with Attention-deficit/hyperactivity disorder (ADHD) are functionally abnormal. The aim of this thesis is to examine the association between H-RSFC and medication status, age, sex, and volumetric asymmetry index (AI). In our approach, region-based activity was obtained using three different methods. To test for associations, two linear mixed-effects models were used. Across results, H-RSFC variation was found in subcortical regions and portions of cortical regions. In addition, changes in functional connectivity were found to be linked with structural asymmetry in two cortical regions. More importantly, shifting in homotopic functional activation was found as a result of medication intake in youths with ADHD. These findings demonstrate the utility of homotopic resting-state functional connectivity for measuring differences among pharmacotherapy intake, gender, neurodevelopment, and structural asymmetry.
  • Characterizing the chemical contaminants diversity and toxic potential of untreated hospital wastewater

    Baasher, Fras (2021-12) [Thesis]
    Advisor: Hong, Pei-Ying
    Committee members: Saikaly, Pascal; Mahfouz, Magdy M.
    This study characterizes 21 wastewater samples collected from Al-Amal hospital between the period of 12 April till 8 July 2020. Al Almal is a hospital that provides drug addiction and psychological treatment to patients. Using solid-phase extraction and liquid chromatography with tandem mass spectrometry (LC-MS/MS), chemical contaminants profiles in these wastewater samples were determined in a non-targeted manner. These chemicals were then individually analyzed in an in-silico manner by checking against databases and literature to determine if they were mutagenic. By determining the proportion of mutagenic chemicals against the non-mutagenic ones, we aim to determine if untreated hospital wastewater may potentially negatively impact the downstream municipal biological wastewater treatment process. It was determined that 64% of the identified chemicals were not tested for their mutagenic effect, and hence no prior information is available in the literature and databases. Instead, we further performed in-vitro mutagenicity tests using Ames test to determine if the wastewater sample, with all of its chemical constituents, would be mutagenic. Ames test results showed that majority of the samples were non-mutagenic except for 1 sample that imposed a mutagenic effect on Salmonella enterica serovar Typhimurium TA98 and 3 samples with mutagenic effect on TA100. In addition, 1 sample showed a toxic effect on TA100. However, in all 5 instances, these samples only imposed a mutagenic and toxic effect at high concentrations of > 10x. The findings in this study suggest that a specialty hospital like Al Amal does not contribute substantially to mutagenic wastewater streams to the municipal sewer, and hence unlikely to significantly perturb the downstream biological treatment processes. However, there may still be a need to consider ad-hoc contributions of mutagenic and/or toxic wastewater streams from the hospitals.
  • Ecologically Friendly Biofunctional Ink for Reconstruction of Rigid Living Systems Under Wet Conditions.

    Avila-Ramírez, Alan; Valle-Pérez, Alexander U; Susapto, Hepi Hari; Perez Pedroza, Rosario; Briola, Giuseppina R; Alrashoudi, Abdulelah; Khan, Zainab; Bilalis, Panagiotis; Hauser, Charlotte (International journal of bioprinting, Whioce Publishing Pte. Ltd., 2021-11-22) [Article]
    The development of three-dimensional (3D)-printable inks is essential for several applications, from industrial manufacturing to novel applications for biomedical engineering. Remarkably, biomaterials for tissue engineering applications can be expanded to other new horizons; for instance, restoration of rigid living systems as coral reefs is an emergent need derived from recent issues from climate change. The coral reefs have been endangered, which can be observed in the increasing bleaching around the world. Very few studies report eco-friendly inks for matter since most conventional approaches require synthetic polymer, which at some point could be a pollutant depending on the material. Therefore, there is an unmet need for cost-effective formulations from eco-friendly materials for 3D manufacturing to develop carbonate-based inks for coral reef restoration. Our value proposition derives from technologies developed for regenerative medicine, commonly applied for human tissues like bone and cartilage. In our case, we created a novel biomaterial formulation from biopolymers such as gelatin methacrylate, poly (ethylene glycol diacrylate), alginate, and gelatin as scaffold and binder for the calcium carbonate and hydroxyapatite bioceramics needed to mimic the structure of rigid structures. This project presents evidence from 2D/3D manufacturing, chemical, mechanical, and biological characterization, which supports the hypothesis of its utility to aid in the fight to counteract the coral bleaching that affects all the marine ecosystem, primarily when this is supported by solid research in biomaterials science used for living systems, it can extend tissue engineering into new approaches in different domains such as environmental or marine sciences.
  • Dual Mode Sensing of Binding and Blocking of Cancer Exosomes to Biomimetic Human Primary Stem Cell Surfaces

    Uribe, Johana; Traberg, Walther C.; Hama, Adel; Druet, Victor; Mohamed, Zeinab; Ooi, Amanda Siok Lee; Pappa, Anna-Maria; Huerta, Miriam; Inal, Sahika; Owens, R. M.; Daniel, Susan (ACS Biomaterials Science & Engineering, American Chemical Society (ACS), 2021-11-21) [Article]
    Cancer-derived exosomes (cEXOs) facilitate transfer of information between tumor and human primary stromal cells, favoring cancer progression. Although the mechanisms used during this information exchange are still not completely understood, it is known that binding is the initial contact established between cEXOs and cells. Hence, studying binding and finding strategies to block it are of great therapeutic value. However, such studies are challenging for a variety of reasons, including the need for human primary cell culture, the difficulty in decoupling and isolating binding from internalization and cargo delivery, and the lack of techniques to detect these specific interactions. In this work, we created a supported biomimetic stem cell membrane incorporating membrane components from human primary adipose-derived stem cells (ADSCs). We formed the supported membrane on glass and on multielectrode arrays to offer the dual option of optical or electrical detection of cEXO binding to the membrane surface. Using our platform, we show that cEXOs bind to the stem cell membrane and that binding is blocked when an antibody to integrin β1, a component of ADSC surface, is exposed to the membrane surface prior to cEXOs. To test the biological outcome of blocking this interaction, we first confirm that adding cEXOs to cultured ADSCs leads to the upregulation of vascular endothelial growth factor, a measure of proangiogenic activity. Next, when ADSCs are first blocked with anti-integrin β1 and then exposed to cEXOs, the upregulation of proangiogenic activity and cell proliferation are significantly reduced. This biomimetic membrane platform is the first cell-free label-free in vitro platform for the recapitulation and study of cEXO binding to human primary stem cells with potential for therapeutic molecule screening as it is compatible with scale-up and multiplexing.
  • 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.

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