“Soft and compliant digital materials for healthcare monitoring”, Alireza Dolatshahi‐Pirouz (DTU)
Alireza Dolatshahi‐Pirouz received his Ph.D. in physics from Aarhus University in 2009 and then took on a postdoctoral‐research position at the Wyss Institute of Biologically Inspired Engineering and Harvard Medical School. He joined Technical University of Denmark as an Assistant Professor in 2015 and later on started his own research group, #TeamBioEngine, at DTU Nanotech.Currently, the group is a part of the newly launched department, Health Technology, and their research lies at the crossroads of biology, engineering, physics, chemistry and biomaterials.
#TeamBioEngine aim to create advanced material innovations based on bioinspired discoveries, and they believe such bioinspired materials and complex nanostructures will drive the engine of the next big revolution in material science. They are trying to explore interesting green solutions in the fields of nanomedicine, electronics and tissue engineering. Along this vein, they introduced Fleco-ionics and Fleconess in 2019, which offers a huge leap forward towards foldable substrates for flexible electronics. What’s more, the team is currently working on developing new self‐healable and stretchable materials with high electrical sensitivity for applications within the emerging fields of flexible electronics, cyborganics, and soft robotics.
In 2018, Alireza Dolatshahi‐Pirouz received a VIDI Grant to further develop his innovative research on regenerative biomaterials at Radboudumc. To date he has published close to 90 papers–most published in medium to high impact journals. He is also a highly cited young researcher with his citations numbering 5045 and an h-index of 42 according to Google Scholar.
“Non-invasive Electrical Stimulation for the Central and Peripheral Nervous System using Temporal Interference”, Adam Williamson (INS)
Adam Williamson is a Principal Investigator at the Institut de Neurosciences des Systèmes (INS), a part of Inserm at Aix-Marseille Université (AMU), France, since April 2014, and a Senior research group leader at the International Clinical Research Center (ICRC), St. Anne’s University Hospital, Brno, Czech Republic, since 2022. He is a recipient of the ERC Consolidator Grant 2023, ERC Starting Grant 2016 and two ERC Proof-of-Concept Grants in 2020 and 2022, using novel technology-based therapies and neuroprosthetics in the treatment of epilepsy. Generally, his research can be classified as technology-based, focused on in vivo applications for new electronic devices and brain stimulation methods in pathophysiological neuronal networks related to epilepsy.
His most cited works have used organic electronic materials, due to their exceptionally attractive properties for neuroscience, including materials with tunable mechanical flexibility, mixed ionic/electronic conduction, enhanced biocompatibility, significantly improved stimulation and recording interfaces, and the capability for drug delivery. Most recently his work is focused on non-invasive deep brain stimulation in Epilepsy using Temporal Interference.
Adam received his B.Sc. degree and M.Sc. degree in Electrical Engineering at Texas Tech University, USA, where his work was focused on the fabrication and optimization of silicon transistors with Professor Richard Gale. In 2011 he received his Ph.D. in Mechanical Engineering at the Technische Universität Ilmenau (TUI), Germany, where his work was focused on the integration of nano-structures into silicon photodiodes with Prof. Martin Hoffmann (the Department of Micromechanical Systems, TUI, Germany). From 2011 to 2014, he worked as a postdoc at TUI with Prof. Andreas Schober (the Department of Nano-Biosystem Technology, TUI, Germany), where his work was focused on nanostructure-enhanced electrophysiology and artificial synapse technology. In 2014 he joined INS in Marseille to focus exclusively on neuroengineering, initially as a post doc with Dr. Christophe Bernard and George Malliaras, and as an independent PI starting in 2016 with the ERC StG.
SESSION 2 - Abstracts
Biosensors, materials, and actuators (Antracit)
“Mesoporous silica particles and films for local drug delivery”, Emma Björk (IFM)
"Mesoporous silica particles and films for local drug delivery" - Emma Björk*
Mesoporous silica particles and films are – with their 2-50 nm large pores, tuneable surface chemistry, and biocompatibility – strong candidates as drug delivery systems. Variations in the synthesis solution, e.g. addition of salts, affects both the particle morphology and the dissolution rate, enabling controlled design of the material. When substrates are added during the material synthesis, it is possible for the particles to nucleate and form a film on the substrate. The films have ~400 nm long, easily accessible pores and can be grown on 3D substrates, making them suitable for implant coatings that can deliver both hydrophilic and hydrophobic drugs.
This presentation will show examples on how mesoporous silica particles and films can be used in medical applications. As an example, mesoporous silica particles have been adsorbed on nanocellulose, loaded with a pH sensitive dye (BTB), and the composite material was used as wound dressing acting as a sensor for infections. Free particles with various shapes have been doped with silver ions to obtain a material with antibacterial activity. It was observed that the particle morphology contributes to killing bacteria. Also, mesoporous silica films were loaded with a hydrophobic model drug (DiO) and C2C12 cells were seeded on the film surface. It was observed that the hydrophobic molecule was stable in the pores, and the delivery mechanism from the pores to the cells was investigated using confocal laser scanning microscopy. The films can be used as a long-time drug reservoir for delivery from medical implants.
“Treating corneal blindness using bioengineered corneas derived from pig skin: a scientific entrepreneurial journey”, Mehrdad Rafat (IMT)
"Treating corneal blindness using bioengineered corneas derived from pig skin: a scientific entrepreneurial journey" - Mehrdad Rafat*
Loss of corneal transparency and integrity are among the leading causes of blindness globally. Although corneal blindness is treatable by cadaver cornea transplantation, an estimated 12.7 million people await a donor cornea, with one cornea available for every 70 needed.
To address these limitations, we bioengineered a cell-free implantable medical device that mimics human corneal tissue in key physical and biological properties. As a raw material we used natural type I collagen, the main protein in the human cornea, but derived from porcine skin which is abundant, cost-effective, and a purified by-product from the food industry.
The bioengineered corneal implants were produced according to the principles of Good Manufacturing Practice and aseptic processing and preclinically tested in vitro and in vivo in animal models. Upon confirming their safety and efficacy preclinically, we tested the implants in more than 20 patients suffering from advanced keratoconus, which is one of the main causes of corneal blindness and low vision. During 24 months of follow-up, no adverse event was experienced. We observed improvements in corneal thickness, steepness, and visual acuity. Vision was restored in all 20 patients 14 of whom were initially blind. This work demonstrates restoration of vision using an approach that is potentially equally effective, safer, simpler and more broadly available than donor cornea transplantation.
“Delivering the right dose, at the right time, at the right place: combining next-level bioorthogonal tools with implantable ion pumps,” Johannes Bintinger (ITN)
"Delivering the right dose, at the right time, at the right place: combining next-level bioorthogonal tools with implantable ion pumps" - Johannes Bintinger*, Nikolaus Porembab, Linda Waldherrc, Theresia Arbring Sjöströma, Iwona Bernacka-Wojcika, Tobias Abrahamssona, Maria Seitanidoua, Daniel Simona, Rainer Schindlc, Hannes Mikulab
a. Laboratory of Organic Electronics, Department of Science and Technology, Linköping University
b. Institute of Applied Synthetic Chemistry, TU Wien
c. Gottfried Schatz Research Center – Biophysics, Medical University of Graz
Biontronics is the combination of Electronic Ion Pumps and Bioorthogonal Release Chemistry which allows us to realize a Chemical Wave Function Generator, capable of controlling chemical delivery with electronic precision, thus translating an electrical signal (frequency and amplitude) into tailormade concentration profiles of (bio)molecules to generate desired biological responses. Using the unique advantages of each technology and outmaneuvering their disadvantages through synergistic combination also solves the decade long problem of Ion Pumps that are thus far limited to the transport of only small molecular weight drugs that are need to be permanently charged. Click-to-release Chemistry on the other hand lacks the programmability and spatiotemporal control of the Ion Pumps.
We show preliminary results of the Biontronic concept using fluorescent experiments and in vitro studies demonstrating the on/off control of cytotoxicity using prodrugs.
To map the large parameter space required for Biontronic applications we have developed a versatile characterization platform which is based on a well-plate compatible ion pump array that allows for simultaneous electrical- and optical characterization. This reproducibility driven approach allows us to readily test and investigate various device geometries, operational modes, bioorthogonal reaction- and release kinetics and iontronic transport efficiencies.
Biontronics will allow us To boldly deliver the right dose at the right place at the right time, where & how no one has delivered before…
“Enzymatically Triggered Lipid Conjugation of Membrane Active Peptides”, Alexandra Iversen (IFM)
"Enzymatically Triggered Lipid Conjugation of Membrane Active Peptides" - Alexandra Iversen*, Johanna Utterström, Robert Selegård, Daniel Aili
Liposomal drug delivery systems are widely used to improve drug pharmacokinetics, but they often suffer from slow and non-targeted release of the active pharmaceutical ingredient (API). Release kinetics can be modulated using membrane-active peptides, but controlling the interactions between the peptides and lipid membranes is challenging. Here we show a novel enzyme-mediated strategy for the conjugation of a de novo designed membrane-active peptide to vesicles.
The peptide is a lysine-rich 42 amino acid helix-loop-helix peptide that triggers lipid membrane destabilization when conjugated to vesicles as a result of peptide folding and partitioning. An N-terminal cysteine enables peptide conjugation to maleimide-functionalized vesicles via Michael addition reaction. Incorporation of a cysteine-protection group, Phacm, on the thiol-moiety prevents undesired thiol-oxidation prior to conjugation. The Phacm group is removed by Penicillin G Acylase (PGA), generating a free thiol that can then react with the maleimide lipids, resulting in a peptide-concentration-dependent release of encapsulated cargo. The possibility to optimize peptide-lipid conjugation provides better means to tune the release process. Additionally, Phacm prevents the issue of thiol-oxidation, allowing for better means of controlling peptide surface concentration. PGA-triggered conjugation of membrane-active peptides to vesicles dramatically facilitates the development of bioresponsive liposome-based drug delivery systems.
“Antimicrobial Peptides in Wound Care: in vivo Efficacy of PNC8 α/β and Functionalization of Advanced Nanocellulose Wound Dressings”, Željana Šotra (IFM) and Elisa Zattarin (IFM)
"Antimicrobial Peptides in Wound Care: in vivo Efficacy of PNC8 α/β and Functionalization of Advanced Nanocellulose Wound Dressings" - Željana Šotra*, Elisa Zattarin*, Jonathan Rakar, Robert Selegård, Emma M. Björk, Johan P.E. Junker, Daniel Aili
Wounds disrupt the natural skin barrier, facilitating pathogen penetration and increasing the risk of infections. Wound infections are a major healthcare concern and can result in patient morbidity and mortality, as well as a substantial cost for the healthcare system. New therapeutic options are required in order to effectively control infections, as the efficacy of traditional antibiotics is now diminishing due to the rise of antimicrobial resistance.
In the present study we demonstrate the antimicrobial activity of the antimicrobial peptides (AMP) Plantaricin NC8 α/β (PLNC8 α/β) using porcine in vivo models. Furthermore, we investigated the possibility of utilizing PLNC8 α/β for wound dressings functionalization. AMP efficacy was investigated on in vivo porcine wound models inoculated with S. aureus (107-8 CFU/g). Topical administration of 100 and 300 µM PLNC8 α/β (1:1) resulted in infection reduction below the clinical relevance of 105 CFU/g and development of neoepidermis. Additionally, combinational therapy with gentamicin completely eradicated the infection seven days post inoculation.
To improve PLNC8 applicability, the peptides were further integrated within nanocellulose-based wound dressings from bacterial and plant origin. The dressings employed for this study were bacterial cellulose (BC), TEMPO-oxidised nanocellulose hydrogel derived from aspen wood (TC) and BC functionalized with mesoporous silica nanoparticles (MSN). AMP loading was obtained through physisorption and proven to minimally impact the dressing properties (moisture transmission, exudate retention, transparency), while retaining dressing biocompatibility.
This study demonstrates the powerful antimicrobial activity of PLNC8 α/β against S. aureus in in vivo porcine wounds and its successful integration within nanocellulose wound dressings for an efficient and controlled treatment of wound infections.
“Antimicrobial peptide-modified bacterial cellulose-silver nanoparticles composite wound dressing for treatment of wound infections”, Wasihun Bekele Kebede (IFM)
"Antimicrobial peptide-modified bacterial cellulose-silver nanoparticles composite wound dressing for treatment of wound infections" - Wasihun Bekele Kebede*, Elisa Zattarin, Zeljana Sotra, Annika Starkenberg, Emanuel Wiman, Sneha Kollenchery Ramanathan, Jonathan Rakar, Robert Salegård, Johan P. E. Junker, and Daniel Aili.
Wounds disrupt the normal function of the skin. Wound infections can delay wound healing and lead to complications resulting in wound chronification. Bacterial cellulose (BC) is an effective wound dressing material but lacks antimicrobial properties and bacteria in the wounds can thrive in the protected environment under the dressing. Strategies to introduce antimicrobial substances in BC, such as silver nanoparticles (AgNPs), and antimicrobial peptides (AMPs) have been extensively explored, but typically involve strategies that requires harsh chemical treatments that are complex, time consuming and may have negative impact on the properties of BC.
We have developed a method based on colloidal self-assembly to create AgNP-BC composite materials. Since the use of AgNPs can be problematic from both a biocompatibility and environmental aspect, we adsorbed a de novo designed AMP on the nanoparticles to be able to reduce the amount AgNPs. We show that the BC-AgNPs can be obtained by means of self-assembly using pre-synthesized AgNPs. The amount of AgNPs could be easily tuned using different concentrations of AgNPs. The BC-AgNP dressings showed a pronounced zone of inhibition (4.5 mm) of Staphylococcus aureus on agar plates. Further functionalization with AMPs resulted in wound dressings with significant antibacterial and bactericidal activity, even for the lowest concentrations of AgNPs used. The proposed strategy simplifies synthesis of AgNP-functionalized BC and provides an affordable antimicrobial wound dressing. The possibilities to further functionalize the AgNPs with AMPs minimizes the need to use excessive concentrations of AgNPs, which decreases cytotoxicity while retaining high antimicrobial activity.
Data analysis, modeling, AI, imaging (Hugo Theorell)
“A scientific journey from modality to AI”, Tomas Bjerner (the CMIV, HMV, radiology)
“Insights into peripheral mechanisms of pain in humans”, Saad Nagi (BKV, CSAN, biomedicine) and Rolf Saager (IMT, WCMM, technical) (joint presentation)
"Insights into peripheral mechanisms of pain in humans" - Saad Nagi* (CSAN) and Rolf Saager* (IMT)
The textbook view is that pain in humans is signaled at a slower speed than touch. Conduction speed is important for several downstream processes and critical in clinical testing to assess nerve function. We have discovered that the pain pathway in humans is not limited to slowly conducting thinly myelinated and unmyelinated primary afferent neurons (nociceptors) but is also equipped with thickly myelinated (Aβ) neurons. These ultrafast nociceptors (UFNs) are insensitive to gentle touch, encode painful mechanical stimuli, and have a conduction velocity similar to Aβ touch neurons. Here, we investigate the role of UFNs in peripheral pain mechanisms at baseline and in experimental conditions mimicking common symptoms of chronic pain such as hypersensitivity to mechanical or thermal stimuli. Initial findings from microneurography (single-unit in vivo electrophysiology in awake humans) on UFN responses during noxious heating-evoked acute inflammation will be discussed. In future work, nerve recordings will be paired with psychophysics and optical imaging to directly compare nerve function with behavioral changes and measures of skin reactivity to inflammation.
“A Unified Minimal Framework to Study Liver Steatosis Dynamics in Response to Different Diet and Drug Interventions”, Christian Simonsson (IMT, HMV and CMIV)
"A Unified Minimal Framework to study Liver Steatosis Dynamics in Response to Different Diet and Drug Interventions" - Christian Simonsson* 1,3,4, Elin Nyman 1, Peter Gustafsson 2, Martin Falk 2, Mattias Ekstedt5, Ingrid Hotz2, Peter Lundberg3,4, Gunnar Cedersund1,3
1 Department of Biomedical Engineering (IMT), Linköping University
2 Department of Science and Technology (ITN), Linköping University
3 Center for Medicine Imaging and Visualization Science (CMIV), Linköping University
4 Department of Radiation Physics and Department of Medical and Health Sciences, Linköping University
5 Department of Gastroenterology and Hepatology, Department of Health, Medicine and Caring Sciences, Linköping University
The obesity epidemic has increased the prevalence of non-alcoholic fatty liver disease (NAFLD) now affecting almost a third of adults worldwide and with an increasing burden on healthcare. NAFLD is characterized by the ectopic storage of triglycerides in hepatocytes and is also denoted steatosis. Steatosis is not inherently dangerous, but it can develop into serious conditions such as hepatic inflammation (NASH), fibrosis and even cirrhosis. Fortunately, steatosis is a reversable condition, and can be treated e.g., via lifestyle interventions such as weight-loss. However, adherence to lifestyle interventions can vary between patients, and further motivational tools could be needed in the future.
In an effort to increase understanding about steatosis, we here introduce a novel minimal modelling and visualization framework for steatosis development and amelioration. The framework incorporates a novel dynamic model for how different fat fluxes contribute to hepatic ectopic fat: de novo lipogenesis, dietary lipid uptake, etc. The model can describe short-and long-term data from a wide variety of different intervention studies, and can also predict new independent data, not used for training the model. The framework also integrates a novel visualization approach, which is combined with model simulations. The approach is able to visualize the increase or decrease of fat storage in histology images of biopsies, in relation to steatosis development or treatment predicted by the model.
Moreover, our framework connects understanding of the effect of different treatment options on hepatic fat fluxes, with visualized changes in the tissue. We believe that our novel framework potentially can be used as a part of a 'Digital Twin'-based eHealth platform, which in the future could be used to improve compliance to lifestyle interventions, thereby reducing the burden of NAFLD and its complications.
“A collaborative in vitro – in silico team effort to describe the inflammatory regulation in human monocytes”, Nilofaar Nickaeen (Örebro University, X-HiDE, mathematical modeling) and Alexander Persson (Örebro University, X-HiDE, cell biology experiments) (joint presentation)
X-HiDE is a consortium founded at Örebro university with the aim of establishing an internationally competitive center of excellence to explore inflammation. In an effort to identify common and distinct characteristics of the inflammatory response across multiple diseases, teams within X-HiDE employ both in vitro and in silico approaches to investigate and describe inflammation as specific core inflammatory phenotypes. The core phenotypes including acute inflammation and immunosuppression are described based on fundamental clinical manifestations of inflammation. One practice of the consortium is to use collaborative in vitro – in silico cycles and develop comprehensive, predictive in silico models, capable of justifying the core phenotypes in primary human monocytes.
In the appointed session, while presenting an overview of our vision and ideas, we will specifically focus on the integrated relation of the in vitro experiments and the in silico simulations throughout building one of our recent models of human monocytic inflammatory response and autocrine regulation. The model was developed to study the interplay between prominent pro and anti-inflammatory cytokines in lipopolysaccharide (LPS) activated primary human monocytes, focusing on the Tumor Necrosis Factor (TNF) and Interleukin 10 (IL-10) -axis. Relevant time-resolved data were generated by experimentally manipulating the effect of IL-10 at different time points and quantifying the cellular output of a selected set of cytokines (TNF, IL-10, IL-1Ra, and IL-1β). The model was successfully trained and could predict independent validation data and was further used to perform in silico experiments to disentangle the role of IL-10 feedbacks in acute inflammation. Overall, we presented a model for further use in studying the complex and dynamic process of cytokine-regulated inflammatory responses in human monocytes and gained detailed insights into the fine-tuning of such responses.
“Beneath the skin: multi-frequency SFDI to detect thin layers of skin using light scattering”, Luigi Belcastro (IMT)
"Beneath the skin: multi-frequency SFDI to detect thin layers of skin using light scattering" - Luigi Belcastro*, Hanna Jonasson, Ahmed Elserafy, Rolf B Saager
Wound healing assessment is usually performed visually by a trained physician, but this type of evaluation is subjective and returns limited information. In contrast, optical imaging techniques are non-invasive ways to quantitatively measure biological parameters. Spatial frequency domain imaging (SFDI) is an optical technique that uses sinusoidal patterns of light at multiple spatial frequencies to measure the tissue absorption and scattering coefficient. While SFDI is based on models that assume the tissue is homogeneous, skin is composed of several layers with different optical properties. An underutilized property of SFDI is that the spatial frequency of the patterns controls the penetration depth of photons. By using multiple ranges of spatial frequencies, we developed a way to obtain morphological data from different volumes of tissue. This data is used to reconstruct the optical properties in depth, allowing us to differentiate between different thin layers of tissue. To validate the accuracy of this method, we have also developed a simple 2-layer optical phantom model that mimics the physiology of wound healing.
“From Death to Data: Postmortem Metabolomics and Multivariate Modelling in Forensic Medicine”, Carl Söderberg (MD, PhD; Rättsmedicinalverket) Liam J. Ward/Albert Elmsjö (PhD; Rättsmedicinalverket)
"From Death to Data: Postmortem Metabolomics and Multivariate Modelling in Forensic Medicine" - Carl Söderberg, Liam J. Ward & Albert Elmsjö
Postmortem metabolomics is a new approach that could help improve cause-of-death diagnoses. The metabolome at time of death likely reflects the agonal period, events preceding death, and potentially the cause of death. Therefore, postmortem metabolomics offers a new perspective for death investigations and biomarker identification. The aim of this presentation is to provide an overview of the postmortem metabolomic workflow, including multivariate statistical modelling, used in research at the National Board of Forensic Medicine (RMV), Sweden.
The workflow involves using retrospective data collected from a standardised drug screening procedure conducted on the majority of forensic autopsies conducted in Sweden between 2017-2020. The data is pre-processed using XCMS in R and data normalised via probabilistic quotient normalisation. A variety of multivariate modelling, including principle component analysis (PCA) and orthogonal partial least squares (OPLS), are used to exclude case outliers, exclude chromatographic features associated with specific background characteristics, and to reduce the number of features to those that are significantly discriminate of the cause of death under investigation. These optimised models can then be used to predict cause of death in separate independent test set of cases.
The presentation will provide examples from previous and ongoing projects to demonstrate the different stages of the postmortem metabolomics workflow. Postmortem metabolomics has the potential to aid forensic death investigations in cause-of-death screening, and this presentation highlights the current workflow being researched at RMV.
eHealth and clinical decision support (Dolomit)
“A decision-support system for intensive care monitoring” (tentative title), Magnus Bång (IDA)
“Promoting health behaviours in migrant women after pregnancy: the PRIMI project”, Pontus Henriksson (HMV)
“ASK FOR IT - Living with Atrial Fibrillation”, Ulla Walfridsson (RN, PhD, Department of Cardiology, RÖ)
A six step internet-based educational program built for and together with patients with atrial fibrillation. The content of the program include; Mechanism of AF, tests and diagnostics, treatments of AF: drugs and cardioversion, treatments of AF: ablation and other treatments, the signiﬁcance of lifestyle and living with AF. The program is evaluated in a pilot study and an RCT is ongoing. The program will soon be available on Stöd & behandling, 1177.
“Exergaming and Gamification to Interrupt Sedentary Behavior - Liopep”, Aseel Berglund (IDA)
“New software platform that calculates and interprets deviation of body temperature and oxygen saturation in relation to individual normal range”, Märta Sund Levander (Department of Nursing)
"New software platform that calculates and interprets deviation of body temperature and oxygen saturation in relation to individual normal range" - Märta Sund Levander*, Ingela Hagman, Ewa Grodzinsky
Precision medicine aims to provide patients with care and treatment tailored to the individual's unique conditions. Current reference ranges for vital parameters are based on healthy, usually male, individuals, excluding people with long-term medical conditions and daily medication. Hence, current interpretation entails a risk of misinterpretation at each measurement occasion because a deviant value for the individual is camouflaged by a normal value at group level. Normal body temperature as 37°C and elevated body temperature in case of fever as > 38°C originates from the middle of the 19th century. However, several studies confirm that normal body temperature is lower than traditionally stated and differs between individuals. Frail elderly people are particularly vulnerable because they often only get non-specific signs and symptoms of infectious diseases. As with body temperature, the definition of the lowest value for normal oxygen saturation also varies; 90%, 95%, 94%, 96%, 97%.
In an ongoing study we have analyzed data on body temperature and oxygen saturation for healthy and frail individuals with various medical conditions. The results show that current general reference values at group level do not match how body temperature actually varies on an individual level. Based on this collected data, we developed an algorithm that calculates and interprets the measurement values related to the individual's normal range. The data is then stored in a cloud backend service. Our intention is that results from the current project will be the basis for continued development and clinical testing of the software platform with our algorithm.
“Non-wearable Persistent Fusion Sensors System with AI for Detection Mental Workload for Pilots and Controllers”, Euclides Lourenco Chuma (IDA, HCS)
"Non-wearable Persistent Fusion Sensors System with AI for Detection Mental Workload for Pilots and Controllers" - Euclides Lourenco Chuma*, Magnus Bång, Jens Alfredsson
This proposed work presents a resilient system of sensors to measure vital signals and motions using sensor fusion techniques and AI to identify cognitive workload and abnormal cardiac signs of pilots and controllers without wearing any wearable device.
To measure the heart rate and breathing rate of the pilot and controllers sitting on a seat were used two types of sensors were for obtaining the heart rate using the Ballistocardiograph (BCG) technique: pressure sensor based on the electromechanical film (EMFs) and high-precision accelerometer sensors based on microelectromechanical (MEMS). These sensors were positioned on the seat, without pilots or controllers wearing anything. A non-contact mmWave radar sensor was used to obtain the heart rate using Micro-Doppler techniques to avoid wrong measures from the unwanted movements in the seat. The heart rate (HR) and respiratory rate (RR) are obtained and analyzed together with heart rate variability (HRV) as variables in the workload identification. This information is then sent to an AI system trained to identify fatigue, cognitive workload situations, and health issues. All this redundant and persistent information feeds a data fusion algorithm based on Kalman filtering, which makes the information more resilient and confident.
“Wound dressing integrated sensors for wound diagnostics”, Olof Eskilsson (IFM)
"Wound dressing integrated sensors for wound diagnostics" - Olof Eskilson1, Elisa Zattarin1, Emma Björk2, Robert Selegård1 and Daniel Aili1.
1Laboratory of Molecular Materials, Division of Biophysics and Bioengineering, Department of Physics, Chemistry and Biology (IFM), Linköping University, SE-58183, Linköping, Sweden
2Division of Nanostructured Materials, Department of Physics, Chemistry and Biology (IFM), Linköping University, SE-58183, Linköping, Sweden
Nanocomposites consisting of bacterial nanocellulose (BC) and nanoparticles (NPs) offer a unique opportunity to create soft and biocompatible materials for biosensing. Nanomaterials allow for miniaturization of sensors that can be integrated into wearable devices for advanced healthcare. Mesoporous silica nanoparticles (MSN) are a particularly promising sensing material due to their large surface area, low toxicity, stability, and well-defined pore structure. Diagnosis of wound infections is currently challenging. Complications from wound infections can be severe, including sepsis, which can be fatal, and wound chronification, leading to a dramatic decrease in quality of life for millions of patients worldwide.
Here we show a functional BC-MSN nanocomposite wound dressing material that can detect infections at an early stage using a pH-sensitive dye, fabricated by self-assembly. By incorporation of pH responsive dyes in the BC-integrated MSNs, the wound dressings undergo a drastic colour change exposed to infect wounds. The high contrast in colour, allow for simple and rapid naked eye readout. This versatile self-assembly based strategy can also be used to create BC composites with gold nanoparticles (AuNPs) for various sensor applications. We functionalized BC-AuNP composites with peptides cleavable by bacteria-secreted proteases. The peptides were further modified with a fluorophore that was quenched due to the short separation to the AuNP surface. When cleaved by proteases excreted by wound pathogens, the fluorescence is recovered.
Wound dressing integrated sensors can allow for patients and healthcare personnel to optimize the treatment and reduce risks with reoccurring infections.
SESSION 4 - Abstracts
Circulation and metabolism (Antracit)
“Interrelationship between hemodynamics and vascular disease explored with magnetic resonance imaging”, Petter Dyverfeldt (HMV and CMIV)
Petter Dyverfeldt is a senior associate professor at the Department of Health, Medicine and Caring Sciences (HMV) and the Center for Medical Image Science and Visualization (CMIV). Dr. Dyverfeldt’s lab develops and applies novel magnetic resonance imaging for studies of hemodynamics and vessel wall disease in cardiac, aortic and carotid artery disease. As a result, they have published 60+ peer-reviewed papers with an h-index of 31, held numerous invited presentations at leading international meetings and been awarded with several large grants including project grants from the Swedish Research Council.
“Complementing MPS with mechanistic computer models help overcome limitations: translating the drug Exenatide from MPS to humans”, Oscar Arrestam (IMT and SUND) and Liisa Vilén (AstraZeneca)
Today, realistic organoids can be combined into microphysiological systems (MPS), which are useful for a growing list of applications. Because of this combination, one can study dynamic cross-talk between organs, otherwise only observable in animals. This improved realism creates the potential to reduce animal experiments, improve drug development efficiency, etc. However, using a purely experimental approach, there are certain limitations that are hard to overcome: the dynamic cross-talk makes data interpretation difficult, and today’s MPS still display critical differences to humans, in terms of functionality, volume differences, and missing organs.
In this presentation, we demonstrate our progress in overcoming these limitations through combining our experimental two-organ MPS, with liver spheroids and pancreas model with a newly developed computer model. The computer model is developed by mechanistic hypothesis testing, and is validated by comparing experiments first done in the computer with subsequent MPS results. Using the validated computer model, we may translate metabolic insights from MPS into making more human and rat-like predictions. Finally, we demonstrate how this translation from two-organ MPS may benefit efficient drug development through studying a specific drug: Exenatide. Translation from MPS provides predictions of human and rat meal responses before and after Exenatide treatment comparable to corresponding in vivo clinical data. In summary, our integrated experimental-computational approach overcomes some of the inherent limitations of MPS, and could help lay the basis for a new type of knowledge-driven drug development.
“Cardiac Blood Flow Simulations and Stasis Assessment in Patients with Atrial Fibrillation”, Sophia Bäck (HMV, CMIV) and Iulia Skoda (HMV and RÖ)
"Cardiac Blood Flow Simulations and Stasis Assessment in Patients with Atrial Fibrillation" - Sophia Bäck*, Iulia Skoda*, Jonas Lantz, Lillian Henriksson, Lars O. Karlsson, Anders Persson, Carl-Johan Carlhäll, Tino Ebbers
In patients with atrial fibrillation (AF), the risk for stroke is increased. The underlying relation between AF and stroke is not fully understood. It has been believed that during phases of active fibrillation, velocities in the left atrium (LA) are reduced, leading to thrombus formation. However, in recent years it has been debated that atrial cardiomyopathy, a disease of the atrial wall, could cause both AF and stroke. The aim of this study was to investigate atrial blood flow and function in controls and AF patients during sinus rhythm to better understand the correlation between blood stasis and atrial contraction.
Time-resolved computed tomography (CT) data were acquired in AF patients in sinus rhythm and controls. Based on the CT images, the blood velocities were calculated using computational fluid dynamics. To quantify the risk of stasis, the blood residence time was computed.
We found large differences in atrial blood residence time between patients and controls (p<0.001) and a strong correlation between reduced LA ejection fraction and increased average residence time in the LA (R2=0.68, p<0.001).
In conclusion, atrial wall motion is coupled to cardiac flow dynamics and plays an important role when investigating stasis in the LA. Stasis is already increased in AF patients while in sinus rhythm. This shows that the risk for stroke might not only be elevated in phases of fibrillations, but also during sinus rhythm. In the future, parameters based on the cardiac motion and blood residence time could support stroke risk assessment in AF patients.
"Microcirculatory changes before and after endovascular intervention in chronic limb-threatening ischemia using a new multimodal imaging system", Marcus Larsson (IMT) and Sofie Aronsson (RÖ)
"Microcirculatory changes before and after endovascular intervention in chronic limb-threatening ischemia using a new multimodal imaging system" - Sofie Aronsson*, Marcus Larsson*, Martin Hultman, Karl Palm, Tomas Strömberg, Helene Zachrisson, Håkan Pärsson
Chronic limb threatening ischemia (CLTI), is the end stage of peripheral artery disease associated with impaired quality of life, amputation and mortality. Ankle brachial index (ABI) and toe pressure (TP) are the main evaluations of the macrocirculation, while transcutaneous oxygen pressure (TcPO2) is often used for assessment of microcirculation. However, these parameters are weak predictors of wound healing.
We have developed a multimodal imaging system based on multi-exposure laser speckle contrast imaging and multi-spectral imaging processed by neural networks, allowing real-time video-rate imaging of microvascular perfusion and blood oxygen saturation. The aim of this study was to evaluate the microcirculation in CLTI before and after intervention, and compare the result with ABI, TP and TcPO2.
Totally 26 patients with CLTI were included. Of these 21 were successfully revascularized with a restored in-line flow to the ankle. Circulation parameters were measured pre-, early post-intervention (one day), and at one month follow-up. Median perfusion and oxygen saturation values from predefined regions of sole of the foot were calculated during a 10-min recording. Additionally, the perfusion pulsatility was computed. Microcirculation perfusion and pulsatility and TP increased significantly one day after intervention, while tcP02 didn’t increase until 1 month follow-up.
In conclusion, this multimodal imaging system is a promising device allowing for global assessment of microcirculatory changes in the whole foot as well as in selected regions of interest. Further studies are warranted to determine the timelines of improved circulation measures and the clinical value of the device.
Neuro (Hugo Theorell)
“Intro to the session - overview of the STRATIF-AI EU project, for prevention, treatment, and rehabilitation of stroke”, Gunnar Cedersund (IMT)
“Microneurography studies of the human somatosensory system”, Håkan Olausson (BKV, CSAN)
“Microneurography studies of the human somatosensory system” - Håkan Olausson* (BKV, CSAN)
A method for percutaneous recording from human peripheral somatosensory afferents was introduced in the mid-sixties by Hagbarth and Vallbo. With this so called microneurography technique our laboratory has demonstrated that there are unmyelinated, slowly conducting primary afferents signalling touch and large myelinated rapidly conducting afferents signalling pain. This contrasts with the textbook view that unmyelinated afferents signal pain, temperature, and itch, but not touch, and large myelinated afferents signal touch, but not pain. In this talk I will address the basic mechanisms as well as functional relevance of the slow touch and fast pain systems. I will take a translational approach and report findings ranging from microneurography recordings in healthy subjects to patient observations. I will also describe ongoing work where we are integrating results from RNA sequencing of human dorsal root ganglion with results from microneurography recordings.
“Hearing skull-bone vibrations”, Stefan Stenfelt (BKV)
“Deep Transcranial Magnetic Stimulation as a non-invasive brain stimulation treatment for alcohol addiction”, Markus Heilig, (BKV, CSAN)
“Probabilistic mapping of deep brain stimulation effect”, Teresa Nordin (IMT)
"Probabilistic mapping of deep brain stimulation effect" - Teresa Nordin*, Dorian Vogel, Erik Österlund, Johannes Johansson, Anders Fytagoridis, Simone Hemm, Karin Wårdell
Deep brain stimulation (DBS) is an established therapy for symptom alleviation in different movement disorders. Although the evidence of the method is substantial, the true mechanism of action is still unknown, and the optimal locations for stimulation are debated. With electric field simulation, the volume of tissue impacted by the stimulation can be estimated at the patient level. However, to investigate the optimal target location group analysis is required. This work presents a method where the patient’s preoperative MRI images are used in a normalization process to produce a cohort-specific template space based on 77 patients with essential tremor. Electric field simulation results from all patients were then transformed to the template space for statistical analysis. For analysis, the mean improvement was estimated in each voxel. A voxel-wise statistical test was then performed where the voxel mean was tested against the overall mean in the entire cohort. The result shows that a high improvement can be found in a large region within the targeting area, indicating high improvement generated from two commonly used targets, the Vim in the thalamus and zona incerta.
In conclusion, a workflow for spatial evaluation of the DBS effect was developed and the result showed that high improvement can be retrieved by stimulating several sub-regions in the thalamic and subthalamic areas.
Multifuctional Nanocellulose Composite Wound Dressings
Elisa Zattarin, Olof Eskilsson, Emma Petterson, Linn Berglund, Kristiina Oksman, Kristina Hanna, Jonathan Rakar, Johan P.E. Junker, Robert Selegård, Emma M. Björk and Daniel Aili.
Inverse problems for biomedical models of brain tumor evolution
Lukáš Malý, George Baravdish, Tomas Johansson, Olof Svensson
Repeated ASL Measurements as a Method for Detection of Altered Cerebral Blood Flow in Patients in the Neurointensive Care Unit
Sofie Tapper, Sandra Wyss, Karin Wårdell
Digital twins and hybrid modelling for simulation of physiological variables and stroke risk
Tilda Herrgårdh, Elizabeth Hunter, Kajsa Tunedal, Gunnar Cedersund
An interconnected multi-level mechanistic model of the human brain
Nicolas Sundqvist, Henrik Podéus, Sebastian Sten, Salvador Dura-Bernal, Fredrik Elinder, Soroush Safaei, Maria Engström, Gunnar Cedersund.
Design and evaluation of a novel Transillumination SFDI system for quantitative assessment of tissue sections for rapid, label-free cancer margin detection
Merel Younan, Johannes Johansson, Rolf B Saager
Development of line scanner for tomographic blood flow measurements in burn wounds
Johannes D. Johansson and Rolf Saager
Spatiotemporal analysis of flowmotion videos in skin microcirculation
Martin Hultman, Marcus Larsson, Tomas Strömberg, Joakim Henricson, Fredrik Iredahl, Ingemar Fredriksson.
Detection of local motion artifacts and image background in Multi Exposure Laser Speckle Contrast Imaging
Johannes Nyhlén, Märta Sund.
A study on Liver Metabolism
Karin Hedin, Cecilia Jönsson, Nina Grankvist, Nicolas Sundqvist, Daniel Racho, Kyumi Byun, Roland Nilsson, Gunnar Cedersund
A comprehensive mechanistic model of adipocyte signaling - with layers of confidence
William Lövfors, Cecilia Jönsson, Charlotta S Olofsson, Elin Nyman, Gunnar Cedersund.
Analysis of multispectral images using ANNs trained on in vivo data for estimation of hemoglobin oxygen saturation in skin microcirculation
Maria Ewerlöf, Tomas Strömberg, Marcus Larsson, E. Göran Salerud.
Real-time indication of tissue characteristics in frameless brain tumor biopsies
Elisabeth Klint, Johan Richter, Karin Wårdell.
Hemodynamic effects of hypertension and type 2 diabetes
K. Tunedal, F. Viola, B. Casas Garcia, A. Bolger, F.H. Nyström, C.J. Östgren, J. Engvall, P. Lundberg, P. Dyverfeldt, C-J. Carlhäll, G. Cedersund, T. Ebbers.
Can you trust your model?
Nicolas Sundqvist, William Lövfors, Gunnar Cedersund
Non-wearable Fusion Sensors System withAI for Detection of Cognitive Workload for Pilots and Controllers
Euclides Lourenco Chuma, Magnus Bång, Jens Alfredsson
Demonstration of the present status of the Tissue Viability Imaging (TiVi) technology for mapping the tissue local red blood cell concentration and other tissue parameters. The Tissue Viability Imager TiVi700 2.0 can be operated both in camera-mode and video-mode. The inherent immunity to movement artefacts makes it suitable for investigation of the microcirculation also in moving objects. Powerful analysis software facilitates batch-mode analysis of erythema and blanching. All data generated exportable to spreadsheets for further processing. The complete Product Sheets and TiVi manuals as well as a TiVi Training course can be downloaded from or viewed at www.wheelsbridge.com.
We are open for discussions of new joint TiVi application projects and collaborations in the field of microvascular research and related areas.
Contact: Gert Nilsson
Advanced Tissue Simulating Optical Phantoms - a LiU Resource
This resource enables a fundamental shift in early medical device development that replaces animal use to evaluate instrument performance and accuracy with physical proxies that are constructed specifically to mimic human tissue over a range of pathological states while also covering normal biological variances (such as skin pigmentation, diet, age, etc.). Here, not only can these proxies, otherwise known as “tissue simulating phantoms,” remove the need for animal experiments and all of its associated costs and oversight, but it can also evaluate the optical device’s sensitivity to other known sources of biological variance and thereby provide constructive feedback on the device design and performance. Lastly, these proposed phantoms are inert, stable over time, and independently traceable. These can also provide a Gold Standard to evaluate the device performance not just in its developmental stage, but again when it is seeking clearance for medical use.
Contact: Rolf Saager
Our company specializes in developing sensor systems that use nanoplasmonic detection to enable real-time monitoring of biopharmaceutical processes. Our mission is to provide innovative solutions that enable our clients to obtain accurate and reliable data for their research and development needs in the biopharma industry.
At the exhibition hall, we will be showcasing our latest sensor system that can detect and analyze monoclonal antibodies and other relevant biopharmaceutical molecules. Our team of experts has extensive experience in this field and is committed to delivering high-quality products and services to our clients.
We believe that our sensor systems have the potential to transform the way biopharmaceutical processes are monitored, and we are excited to share our expertise with attendees at the event. We look forward to connecting with like-minded individuals who share our passion for scientific innovation and advancing research and development in the biopharma industry.
Contact: Motasam Majedy
SUND sound medical decisions - “Come and test your own digital twin”
Come and see how you can create your own digital twin. Our digital twins look like you on the outside (skin, face, body type, clothes, etc), and on the inside (inside the organs, and inside the cells). You can make your twin do things - move, exercise, eat, change its diet or take medications - and see what happens, inside the body; both acutely while it happens, and over weeks, months and years, if you would do those things every day. We have prototypes of apps for how to use these twins in patient-doctor communications, in education, and in entertainment. The digital twins are already used to support drug development within the pharma industry.
Aktiebolaget SUND sound medical decisions, Gunnar Cedersund’s research group at IMT, and the National Research Infrastructure InfraVis.
Kiwok Nordic AB
(Information in Swedish) Kiwok bjuder in forskare och kliniker till samverkan inom utveckling av avancerad distansmonitorering (RPM) för hållbar och preventiv hälsovård. Vi har idag fokus på kontinuerlig monitorering och tidig diagnos av hjärtat men vill bredda erbjudandet till att även mäta andra terapiområden. Vi vill skapa en individuell hälsoprofil för våra användare och visualisera analysen av flera mätvärden i en begriplig vy.
Contact: Anders Östlund
LinkoCare Life Sciences AB
LinkoCare Life Sciences AB is a knowledge-intensive bioengineering start up looking for a Production Engineer to join its dynamic team at the company’s facility at Linköping Science Park in Linköping, Sweden. LinkoCare is conducting innovative Research and Development and pilot manufacturing of bioengineered products close to commercialization stage. Our core value is to offer hope and make an impact by improving vision, patient care, and life quality for the estimated 23 million people worldwide suffering from corneal related disease. LinkoCare first goal is to provide the society with safe bioengineered corneal implants that meet the urgent demand of the world population suffering from corneal blindness and low vision.
Contact: Alin Balian
Contact: Ingemar Fredriksson