Détection de l’activité cérébrale par des nanoparticules superparamagnétiques d’oxide de fer

La détection précise des régions du cerveau abritant une activité électrique accrue joue un rôle central dans la compréhension et le traitement de maladies telles que l'épilepsie. Parallèlement à l'activité électrique, le cerveau produit des champs magnétiques à partir de l'activité électrique neuronale. Cette étude explore une nouvelle méthode de détection de l'activité cérébrale basée sur l'agrégation de nanoparticules superparamagnétiques d'oxyde de fer (NPSOF) par les champs magnétiques neuronaux. Les nanoparticules superparamagnétiques d'oxyde de fer (NPSOF) peuvent réagir aux champs magnétiques en s'agrégeant et représentent un potentiel candidat en tant que nouvel indicateur de l'activité neuronale. Nous avons émis l'hypothèse que les NPSOF à proximité de tissus cérébraux actifs s'agrégeraient proportionnellement à l'activité électrique neuronale. Nous avons également supposé que cette agrégation pourrait être détectée en utilisant l'imagerie par résonance magnétique (IRM), une modalité sensible aux changements de susceptibilité magnétique. Nous avons utilisé une approche expérimentale par étapes, prouvant d'abord le concept en utilisant des tranches de cerveau de rats gardées actives et en observant l’agrégation en direct sous microscopie. Nous avons ensuite utilisé un modèle similaire de tranches de cerveau de rats in vitro avec une activité réglable. Dans cette deuxième partie des expérimentations, après exposition à divers degrés d'activité, l'agrégation a été évaluée en utilisant l'IRM et la diffusion dynamique de la lumière (Dynamic light scattering, - DLS). Nous avons ensuite réalisé une première étude de faisabilité dans un modèle de rat épileptique in vivo. Nous avons constaté que l'augmentation de l'activité des tranches de cerveau était associée à des niveaux plus élevés d'agrégation mesurés par DLS, ce qui suggère que les champs magnétiques générés par le tissu neuronal pourraient induire une agrégation des NPSOF à proximité. Nous avons également constaté que les changements liés à l'agrégation des NPSOF peuvent modifier le signal IRM (temps de relaxation T2), permettant une détection de l'agrégation non invasive combinée à la résolution spatiale et aux capacités d'imagerie de l'IRM. Dans les expériences in vivo, l'activité cérébrale a été associée à une agrégation de NPSOF lorsque évaluée par IRM. Par contre, le modèle animal in vivo s’est démontré sous-optimal pour confirmer si l'activité épileptique peut engendrer une agrégation plus importante de NPSOF par rapport à l'activité cérébrale normale. Ces travaux confirment le potentiel des NPSOF pour détecter l'activité épileptique cérébrale. Les changements de signal à l’IRM induits par l'agrégation de NPSOF peuvent s’avérer un outil puissant pour la détection de l'activité électrique du cerveau à l'aide de NPSOF.----------ABSTRACT Precise detection of brain regions harbouring heightened electrical activity plays a central role in the understanding and treatment of diseases such as epilepsy. Along with electrical activity, the brain produces magnetic fields from neuronal electrical activity. We explore in this thesis a new method of detection of electrical brain activity based on the aggregation of superparamagnetic iron oxide nanoparticles (SPIONs) under neuronal magnetic fields. Superparamagnetic iron oxide nanoparticles (SPIONs) can react to magnetic fields by aggregating and represent an interesting new candidate to monitor neuronal activity. We hypothesized that SPIONs in close vicinity to active brain tissue would aggregate proportionally to the neuronal electrical activity. We also supposed that this aggregation could be detected using magnetic resonance imaging (MRI), a modality that is sensitive to changes in magnetic susceptibility. We used a stepwise experimental approach, first proving the concept of aggregation in living rats brain slices. We then used an in vitro rats brain slices model with adjustable activity. In that second portion of the experimentations, after exposure to various degree of activity, aggregation was assessed using MRI and dynamic light scattering (DLS). We finally performed a first feasibility study in an in vivo epileptic rat model. We found that increasing brain slice activity was associated with higher levels of aggregation as measured by dynamic light scattering (DLS), suggesting that the magnetic fields generated by neuronal tissue could induce aggregation in nearby SPIONs in solution. We further found that the aggregation-related changes in SPIONs solutions can change the MRI signal (T2 relaxation time), allowing non-invasive aggregation detection combined to the spatial resolution and imaging capabilities of MRI. In the in vivo experiments, brain activity was associated with increased aggregation as assessed with MRI, but the animal model was suboptimal to confirm if epileptic activity can be differentiated from normal brain activity using SPIONs. This work confirms the potential of SPIONs to serve as a sensor of brain epileptic activity. MRI signal change induced by SPIONs aggregation can serve as a powerful tool for detection of brain electrical activity using SPIONs

Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications

Peptide– and protein–nanoparticle conjugates have emerged as powerful tools for biomedical applications, enabling the treatment, diagnosis, and prevention of disease. In this review, we focus on the key roles played by peptides and proteins in improving, controlling, and defining the performance of nanotechnologies. Within this framework, we provide a comprehensive overview of the key sequences and structures utilised to provide biological and physical stability to nano-constructs, direct particles to their target and influence their cellular and tissue distribution, induce and control biological responses, and form polypeptide self-assembled nanoparticles. In doing so, we highlight the great advances made by the field, as well as the challenges still faced in achieving the clinical translation of peptide- and protein-functionalised nano-drug delivery vehicles, imaging species, and active therapeutics

Fifteenth Annual Summer Research Symposium Abstract Book

2019 summer volume of abstracts for science research projects conducted by students at Trinity College

Conformable transistors for bioelectronics

The diversity of network disruptions that occur in patients with neuropsychiatric disorders creates a strong demand for personalized medicine. Such approaches often take the form of implantable bioelectronic devices that are capable of monitoring pathophysiological activity for identifying biomarkers to allow for local and responsive delivery of intervention. They are also required to transmit this data outside of the body for evaluation of the treatment’s efficacy. However, the ability to perform these demanding electronic functions in the complex physiological environment with minimum disruption to the biological tissue remains a big challenge. An optimal fully implantable bioelectronic device would require each component from the front-end to the data transmission to be conformable and biocompatible. For this reason, organic material-based conformable electronics are ideal candidates for components of bioelectronic circuits due to their inherent flexibility, and soft nature. In this work, first an organic mixed-conducting particulate composite material (MCP) able to form functional electronic components and non-invasively acquire high–spatiotemporal resolution electrophysiological signals by directly interfacing human skin is presented. Secondly, we introduce organic electrochemical internal ion-gated transistors (IGTs) as a high-density, high-amplification sensing component as well as a low leakage, high-speed processing unit. Finally, a novel wireless, battery-free strategy for electrophysiological signal acquisition, processing, and transmission that employs IGTs and an ionic communication circuit (IC) is introduced. We show that the wirelessly-powered IGTs are able to acquire and modulate neurophysiological data in-vivo and transmit them transdermally, eliminating the need for any hard Si-based electronics in the implant

2013 IMSAloquium, Student Investigation Showcase

This year, we are proudly celebrating the twenty-fifth anniversary of IMSA’s Student Inquiry and Research (SIR) Program. Our first IMSAloquium, then called Presentation Day, was held in 1989 with only ten presentations; this year we are nearing two hundred.https://digitalcommons.imsa.edu/archives_sir/1005/thumbnail.jp

Building And Validating Next-Generation Neurodevices Using Novel Materials, Fabrication, And Analytic Strategies

Technologies that enable scientists to record and modulate neural activity across spatial scales are advancing the way that neurological disorders are diagnosed and treated, and fueling breakthroughs in our fundamental understanding of brain function. Despite the rapid pace of technology development, significant challenges remain in realizing safe, stable, and functional interfaces between manmade electronics and soft biological tissues. Additionally, technologies that employ multimodal methods to interrogate brain function across temporal and spatial scales, from single cells to large networks, offer insights beyond what is possible with electrical monitoring alone. However, the tools and methodologies to enable these studies are still in their infancy. Recently, carbon nanomaterials have shown great promise to improve performance and multimodal capabilities of bioelectronic interfaces through their unique optical and electronic properties, flexibility, biocompatibility, and nanoscale topology. Unfortunately, their translation beyond the lab has lagged due to a lack of scalable assembly methods for incorporating such nanomaterials into functional devices. In this thesis, I leverage carbon nanomaterials to address several key limitations in the field of bioelectronic interfaces and establish scalable fabrication methods to enable their translation beyond the lab. First, I demonstrate the value of transparent, flexible electronics by analyzing simultaneous optical and electrical recordings of brain activity at the microscale using custom-fabricated graphene electronics. Second, I leverage a recently discovered 2D nanomaterial, Ti3C2 MXene, to improve the capabilities and performance of neural microelectronic devices. Third, I fabricate and validate human-scale Ti3C2 MXene epidermal electrode arrays in clinical applications. Leveraging the unique solution-processability of Ti3C2 MXene, I establish novel fabrication methods for both high-resolution microelectrode arrays and macroscale epidermal electrode arrays that are scalable and sufficiently cost-effective to allow translation of MXene bioelectronics beyond the lab and into clinical use. Thetechnologies and methodologies developed in this thesis advance bioelectronic technology for both research and clinical applications, with the goal of improving patient quality of life and illuminating complex brain dynamics across spatial scales

Graphene Based Ion Sensitive Field Effect Transistor for K+ Ion Sensing

Graphene, discovered in 2004, has drawn great interest in the wide range of applications due to its distinctive 2-dimensional material property. Sensing is the one application has been developed extensively owing to graphene’s ultra-high mobility, low electric noise, very high surface-to-volume ratio, and easy modulation of electrical characteristics. With these excellent properties, the present research explored graphene’s ion sensing potential with the goal of developing graphene-based K+ ion detector which can be applicable in implantable bio-sensors. As the major intracellular cation, potassium has very critical functions in various biological processes. Additionally, recent research found out that elevations in biological levels of K+ ions precede the onset of sudden cardiac death, epileptic seizures, and other clinical problems. Therefore, the development of implantable K+-sensitive sensor devices could be of great use in predicting the onset of those time-sensitive condition breakouts in medical applications. To synthesize high quality graphene to investigate graphene’s property and explore its ion sensing capability, a CVD system was built in the lab along with an automatic control program that can both control and monitor the synthesis process. Characterization was carried out with various tools (AFM, Raman spectroscopy, Hall measurement and etc.) and the results confirmed that the obtained graphene is high quality mono-layer graphene. In order to have a deeper insight into graphene’s sensing mechanism, graphene’s interactions with typical donor/ acceptor gas molecules and strong donor molecules were investigated by observing its three important electrical properties – carrier mobility, carrier density, and sheet conductivity change upon molecular adsorption. From the investigation, an empirical model was proposed to explain an interesting trend of graphene’s transport property changes during its molecular interactions. On the other hand, an advanced surface functionalization method was developed to greatly enhance graphene’s molecular sensing performance. A light oxygen plasma treatment can boost graphene’s electrical response to NH3 molecules both in response magnitude and response time. A systematic analysis was carried out and found an optimum power of oxygen plasma can induce a surface functionalization caused by graphene crystal grain size nano crystallization and oxygen species p-doping effect. Graphene-based ion sensitive field effect transistors (GISFETs) with high sensitivity and selectivity for K+ ion detection was demonstrated utilizing valinomycin based ion selective membrane. The performance of the GISFETs was studied in various media over a concentration range of 1 M – 2 mM. The sensitivity of the sensor was found to be \u3e60 mV/decade, which is comparable to the best Si-based commercial ISFETs, with negligible interference found from Na+ and Ca2+ ions in high concentration. The performance of the sensor also remained unchanged when fabricated on a flexible and biocompatible PET substrate. The sensor performance did not change significantly in Tris–HCl solution or with repeated testing over a period of two months highlighting its reliability and effectiveness for physiological monitoring. From Real-cell based extracellular K+ ion assay, the GISFET sensor demonstrated good detecting performance confirmed the possibility of using in implantable bio sensing application. Additionally, GISFET sensor arrays fabricated using CMOS compatible technique also showed the same sensing performance which proves mass production capability in the future. At the same time, graphene based ion sensitive diode (G-ISDiode) was also developed using graphene/silicon Schottky junction. Because of the exponential relation between diode current and graphene’s Fermi level, the G-ISDiode sensor demonstrated an exponential sensing performance in ionic detection. This is different from G-ISFET’s linear response to ion concentration, which can be a big advantage in certain applications where demand ultra-high sensitivity

Celebrating Applied Sciences Reaches 20,000 Articles Milestone

To celebrate the publication of 20,000 articles in Applied Sciences, we launched this Special Issue “Celebrating Applied Sciences Reaching Its 20,000 Article Milestone: Feature Papers of the Applied Biosciences and Bioengineering Section”. We have invited well-known experts in different areas of interest covered in “Applied Biosciences and Bioengineering” to submit their original research papers and review articles of the highest quality in celebrating together with our readers on this special occasion. This Special Issue has collected more than 10 papers featuring important and recent developments or achievements in biosciences and bioengineering, with a special emphasis on recently discovered techniques or applications