Participant’s abstracts

Scientific Poster session jury
Silvia Generelli (CSEM)
Bruno Schnyder (HES-SO Valais)
Jakob Weber (Bühlmann Laboratories AG)
Prof Dominik Meinel (FHNW)

#1

Applications of focal molography in diagnostics, bioprocessing and drug discovery

A.Frutiger(1), V.Gatterdam(1), A.M.Reichmuth(2), Y.Blickenstorfer(2), Christof Fattinger(3), Janos Vörös(2)

1) Lino Biotech AG, Gloriastrasse 35, 8092 Zürich, Switzerland
2) Laboratory of Biosensors and Bioelectronics, Institute of Biomedical Engineering, University and ETH Zürich, 8092 Zürich, Switzerland
3) Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.

Focal molography is a new label-free detection method, which allows the real-time investigation of complex molecular interactions in the presence of a complex biological environment without any stabilization or equilibration (1–3). Thereby, opening up new perspectives and possibilities in drug discovery, bioprocessing or diagnostics and related disciplines. In particular, we have shown an interesting approach to diagnostics based on real-time immunosignaturing(4). This approach utilizes an array of molographic sensors to discriminate between different health conditions in a real-time direct binding assay format. We demonstrated the proof of principle with plasma profiling of different hemagglutinin-like peptides to discriminate different blood donors. In addition, we demonstrate other non-diagnostic applications of focal molography including the determination of binding parameters in complex samples(3), the characterization of membrane proteins in living cells5 as well as the real-time observation of cytosolic proteins in living cells(6). As the figure summarizes the features of focal molography make it an ideal technology for future miniaturized point of care devices.

  1. Frutiger, A. et al. Principles for Sensitive and Robust Biomolecular Interaction Analysis: The Limits of Detection and Resolution of Diffraction-Limited Focal Molography. Phys. Rev. Applied 11, 014056 (2019).
  2. Fattinger, C. Focal Molography: Coherent Microscopic Detection of Biomolecular Interaction. Phys. Rev. X 4, 031024 (2014).
  3. Gatterdam, V. et al. Focal molography is a new method for the in situ analysis of molecular interactions in biological samples. Nat. Nanotechnol. 12, 1089–1095 (2017).
  4. Reichmuth, A. M. et al. Investigating Complex Samples with Molograms of Low-Affinity Binders. ACS Sens (2021) doi:10.1021/acssensors.0c02346.
  5. Reichmuth, A. M. et al. Quantification of Molecular Interactions in Living Cells in Real Time using a Membrane Protein Nanopattern. Anal. Chem. 92, 8983–8991 (2020).
  6. Incaviglia, I. et al. An Approach for the Real-Time Quantification of Cytosolic Protein-Protein Interactions in Living Cells. ACS Sens 6, 1572–1582 (2021).

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#2

Assay conditions improvement for electrochemical lateral flow assay for CRP quantification

Petruzzi Loric(1), Maier Thomas(1), Hainberger Rainer(1)

1) AIT Austrian Institute of Technology GmbH, Vienna, Austria

Lateral flow devices (LFD) are part of the diagnostic toolset that enables point-of-care (POC) testing and aims at allowing any individual to perform an affordable medical test in a short amount of time and without specialized equipment. Most LFDs are based on nanoparticle labels and are primarily used for qualitative tests via visual inspection (e.g. pregnancy tests). By taking advantage of technological advances in sensing technology, some progress has been made to apply LFDs also for quantitative results.

Our approach for a quantitative LFD is based on electrochemistry, where a measurable current is generated by using an enzyme-labelled conjugate followed by a locally electrically induced oxidation. In this context, we have studied some of the most crucial points included in the effort-, time-, and cost-intensive development of a quantitative POC LFD.

Some of these points involve an optimal composition and preparation of the conjugate, a well thought geometry and disposition of the LFD elements, and the setup of a proper and accurate sensing interface. Improving these parameters directly impacts the assay performance and, thus, all represents paramount steps during the realization of high quality quantitative LFDs.

In the end, the results gave a better insight into the mechanisms governing our electrochemical LFD approach and provided improvements regarding the concentration dependence of the signal for a quantitative C-reactive protein (CRP) LFD.

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#3

NIIDS—Digital Urine Analysis with Printed Electrochemical Sensors

N. Glaser(1), D. Migliorelli(1), M. Zinggeler(1), L. Burr(1), K. Petropoulos(1), H. Gao(1), L. Mühlebach(1), R. Junuzovic(1), N. Schmid(1), F. Geister(1), S. Fricke(1), S. Paoletti(1), C. Abongomera(2), D. Paris(2), S. Generelli(1)

1) CSEM Centre Suisse d’Electronique et de Microtechnique SA, Bahnhofstrasse 1, CH-7302 Landquart, Switzerland
2) Swiss Tropical and Public Health institute (TPH), Socinstrasse 57, 4051 Basel, Switzerland

There is a need for developing new solutions that enable rapid diagnostic tests in low resource settings. CSEM is working on the development of a handheld fluidic cartridge, containing an array of printed electrochemical sensors for the digital recording of urinary glucose and pH. The system is being developed for the Swiss Tropical and Public Health Institute (Swiss TPH) to assist clinical decision making in low-resource settings such as refugee camps.

Clinical decision making in low-resource settings is often based on limited diagnostic information. Inaccurate treatment of febrile illnesses (e.g. by broadband antibiotics) is often the consequence. The Swiss TPH aims to develop a diagnostic tool for the most common pathogens and febrile illnesses, to fight migrant diseases. Nowadays, basic urinalysis is done with urine paper dipsticks with colour indicators.

We have developed a digital sensing device to detect important ions and metabolites in urine. Among these are pH, sodium and glucose. Sensors for glucose and pH have been realized on the device and showed good results in first urine tests. Our printed pH sensors show excellent agreement with the reference system and very good sensor reproducibility. Glucose can be measured with higher sensitivity compared to urine dipsticks, which may allow to detect diabetes at an early stage. Later, sensors for additional analytes, such as sodium and lactate, will be added to the device array.

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#4

Single-walled carbon nanotube-based optical hydrogel films for glucose monitoring in cell cultures

Vitalijs Zubkovs, Emilie Vuille-dit-Bille, Hui Chai-Gao, Miha Markocic, Stefano Cattaneo

Swiss Center for Electronics and Microtechnology (CSEM), Center Landquart, Landquart, Switzerland

During cell culturing bio-analytes, such as glucose, are monitored to maintain optimal cell culture growth conditions. It is vital for cell health that glucose levels are maintained during cell growth. Therefore, glucose is typically manually monitored in most of the small and medium scale bio-reactors and cell culture flasks. Autonomous glucose monitoring provides continuous control of the analyte during the culturing process, reduces the time of cell culture surveillance by technical personnel, and reduces the risk of contamination.

We develop an optical sensor for continuous glucose monitoring in cell cultures. The sensor is based on a nanocomposite comprising semiconductive single-walled carbon nanotube (SWCNT) and bio-engineered glucose oxidase (GOx). To create a functional sensing layer, the SWCNT/GOx composites are immobilized in a hydrogel matrix. The hydrogel is optically transparent to the fluorescence emission of SWCNTs, permeable to glucose molecules, bio-compatible, and non-degradable.

In this study, we immobilized the optical hydrogel/SWCNT/GOx sensor material onto poly(methyl methacrylate) substrates which are inserted into a fluidic device. The sensing layer is illuminated with laser light at 660 nm and the fluorescence signal from SWCNTs is monitored in the near-infrared region between 1000 and 1200 nm. The cell culture media with and without added glucose are circulated through the fluidic device. The fluorescence intensity is recovered to its initial levels once the sensor is in contact with a cell culture medium without supplemented glucose. The hydrogel-based immobilization allows the integration of the sensing material inside cell culture flasks creating glucose-responsive layers, which can be monitored using an external optical reader.

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#5

peakPCR: PCR Diagnostics within minutes

Philippe Bechtold(1,2), Dr. Michele Gregorini(1,2), Prof. Wendelin Stark(1)

1) Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering, ETH Zurich
2) Diaxxo AG, Zurich

The functional materials laboratory has developed an affordable and accurate “Rapid PCR test” with the goal of making advanced DNA analysis available in Point-of-Care and Resource-Limited settings. We routinely deliver full PCR results within 30 minutes and have shown the tests to work within 10 minutes. Our technology allows even inexperienced users to rapidly go from “swab-to-results” and it relies on room-temperature, non-toxic chemicals that can be stored and handled even at tropical conditions. In the past year we have developed test cartridges for Covid-19, Sexually-Transmitted-Infections, Dengue, Malaria and other tropical diseases, thanks also to our strong collaboration with the Swiss Tropical and Public Health Institute (Swiss TPH). Recently our technology has been implemented for a large-scale Schistosomiasis testing campaign in Zanzibar, where our devices and test cartridges are used for the screening of 10’000 children in mobile laboratories arranged in schools across the island. Moreover, in the context of the BRCCH-EDCTP Collaboration Initiative 2020, devices and test cartridges for more than 2’000 patients have been recently delivered to seven different laboratories in Africa for the detection of Covid-19.

In the poster I will show details about the technology of rapid PCR and highlight its uses in a case study.

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#6

Prediction of SARS-CoV-2 infection status and COVID-19 disease severity based on clinical data with Machine Learning

Zhakparov D(1,2,3), Schmid M(4), Styrzynski F(5), Roelke H(4), Solek J(5), Krzystof J(5), Lukasik Z(5), Roqueiro D(6), Makowska J(5), Sokolowska M(1,2) and Baerenfaller K(1,2,3).

1) Swiss Institute of Allergy and Asthma Research, 7065 Davos Wolfgang, Switzerland
2) University of Zurich, 8006 Zurich, Switzerland
3) Swiss Institute of Bioinformatics, Lausanne, Switzerland
4) University of Applied Sciences of Grisons, SII, 7000 Chur, Switzerland
5) Department of Rheumatology, Medical University of Lodz, Lodz, Poland
6) Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland

In the current COVID-19 pandemics, it is of critical importance that SARS-CoV-2 positive patients can be reliably identified already at hospital admission. Moreover, it is important that disease progression of COVID-19 patients is monitored to allow for appropriate and timely treatments.
The aim of our study is to build a decision tree based on clinical data using Machine Learning to find predictors of a possible SARS-CoV-2 infection upon hospital admission. Additionally, we want to see the progression of features that lead to severe illness and a negative outcome.

We trained several models based on different estimators on a dataset containing patient information on comorbidities, pre-medication and on symptoms and laboratory parameters at hospital admission and over the course of the disease for 201 SARS-CoV-2 positive and 314 negative subjects with a COVID-19-like clinical picture at hospital admission. The longitudinal clinical laboratory data was parametrized to observe how these patterns are associated with disease severity and outcome.

We have identified a set of important features that are able to differentiate between SARS-CoV-2 positive and negative patients, and between COVID-19 patients who survived or deceased. Our study therefore managed to provide clinicians with valuable information on a patient’s possible status, based on which the treatment can be planned.

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#7

Towards quantitative and rapid testing of salivary cortisol for stress management

E. Garofano, D. Prim, M. Fraigedo, M. Zollinger and J.-M. Segura

Institute of Life Technologies – School of Engineering; HES-SO // University of Applied Sciences Western Switzerland; Sion; Switzerland

Chronic stress is an increasing burden in our society with major health and economic impact. The percentage of the population reporting insufficient resources to face their sources of stress is continuously growing: 25.4 % in 2016, 27.1 % in 2018 and 29.6 % in 2020. Chronic stress has a considerable impact on health by increasing the risk of developing pathologies such as diabetes, heart illnesses, cancers and burn-out. In Switzerland it is estimated that the healthcare costs caused by chronic stress amount to 30 billion CHF per year. Chronic stress also has an economic impact: Induced losses for Swiss companies are estimated to be 7.6 billion in 2020. Easy-to-use tools to monitor chronic stress would be very helpful to support individual and collective stress management programs. However, while nowadays numerous solutions for the monitoring of instantaneous stress exist such as health watches, analysis of chronic stress is still assessed via the cumbersome quantification of salivary cortisol in central laboratories.

We have initiated a project aiming at providing an easy-to-use instrument for the individual assessment of chronic stress levels using a quantitative lateral flow immunoassay (LFA) for salivary cortisol. Stringent requirements in terms of sensitivity and reproducibility are planned to be met by using fluorescence detection, by a systematic analysis and reduction of the manufacturing variability and by the development of normalization and analysis tools. A compact and easy-to-use fluorescence reader for quantitative analysis of LFA is also under development. We will present our most recent results in the development of this novel LFA.

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#8

Portable tool for analyzing male fertility based on the measurement of sperm concentration and motility

Loris Gomez Baisac(1), Laetitia Nikles(1), Elena Najdenovska(2), Fabien Dutoit(2), Yulia Karlova(3), Alexandre Karlov(3), Olivier Cuisenaire(2), Laura Elena Raileanu(2), Adrien Roux(1)

1) Haute école du paysage, d’ingénierie et d’architecture (HEPIA HES-SO), Geneva, CH
2) Haute école d’ingénierie et de gestion du canton de Vaud (HEIG-VD HES-SO), Yverdon-les-Bains, CH
3) Akymed Ltd., Cheseaux-sur-Lausanne, CH

We have designed a low-cost portable device to carry out essential measurements of semen quality, such as concentration and motility of spermatozoa, outside laboratory conditions. The technology developed guarantees a standardized, reliable, and rapid analysis that meets the medical and veterinary quality.

To ensure minimum cost and maximum accessibility of the device, we have only include the necessary optical, mechanical, and electronic parts. Preprocessing and analysis of the images is carried out on a companion mobile application.

We offer the following characteristics: (i) Compatibility with different microscopy disposable counting chamber slides. (ii) Integration of an easy-to-use mechanical system to focus on cells. (iii) LED-based illumination, which allows sufficient contrast for cell detection. (iv) User-friendly interface to guide the acquisition and analysis processes. (v) Integration of image processing techniques tailored to the quality of the acquired images. (vi) Accurate analysis of relevant parameters for concentration and motility based on the processed images.

The proposed solution differs from similar existing devices on the market by offering to analyze not only the concentration but also the motility of spermatozoa. We have tested with success its use for veterinary diagnostic such as pig and fish.

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#9

Mass spectrometry-based identification of allergen proteins involved in seafood-related allergic reactions

Elena Barletta (1,2), Klemens Fröhlich (5,6), Patrick Westermann (1), Marie-Charlotte Brüggen (3,4), Peter Schmid-Grendelmeier (3,4) and Katja Baerenfaller (1,2)

1) Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland,
2) Swiss Institute for Bioinformatics (SIB), Davos, Switzerland,
3) Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland,
4) Department of Dermatology, University Hospital, Zurich, Switzerland,
5) Institute of Surgical Pathology, Medical Center, University of Freiburg, Freiburg, Germany,
6) Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Shellfish are one of the most common causes of food allergies and a major cause of food-induced anaphylaxis. The prevalence of seafood allergy is higher in populations residing in coastal geographic areas where seafood is an integral part of their diet. Sensitization and subsequent reactions occur most frequently upon ingestion. However, they can also occur because of skin contact. Shrimps are, among all, the most consumed type of seafood worldwide and for that it is important to identify and characterize all possible allergens. A bottom-up proteomics approach, LC-MS/MS coupled with Parallel Reaction Monitoring (PRM) technique, is used to acquire high-resolution full MS/MS spectra for each target allergen peptide. Total protein extracts from shrimp (Penaeus monodon and Penaeus vannamei) were isolated and processed through in-gel tryptic digestion of SDS-PAGE gel fractions or using PreOmics columns with or without fractionation. Resulting peptides were then collected and purified prior to LC-MS/MS analysis and the MS raw files were processed by the SEQUEST algorithm within the protein database for decapods (TaxID = 6683). In all shrimp samples it was possible to accurately identify our proteins of interest. Tropomyosin proteins specific for shrimp, prawns, lobster and crab were identified in our discovery workflow sharing a sequence identity between 89% and 100%. To support our findings, a PRM analysis was then performed looking for all shrimp unique tropomyosin peptides. A transition list for each peptide, from in silico digestion, is generated and analyzed within the Skyline open source software. It was possible to confirm the presence of the tropomyosin allergen and the results obtained suggest the reproducibility of this proteomics workflow, so as to be used not only in the identification of other important allergens in seafood-related allergic reactions but also of allergens involved in other types of allergic diseases.

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#10

Towards an electronic smart patch for glucose and lactate monitoring

S. Kurzhals(1), E. Melnik(1), P. Plata(1), E. Cihan(1), C. Derntl(1), A. Felice(2), P. Herzog(2), A. Bocchino(3), C. O’Mahony(3), G.C. Mutinati(1), R. Hainberger(1)

1) AIT Austrian Institute of Technology GmbH, Center for Health and Bioresources, Molecular Diagnostics, Giefinggasse 4, 1210 Vienna, Austria
2) DirectSens GmbH, Am Rosenbühel 38, 3400 Klosterneuburg, Austria
3) Tyndall National Institute, University College Cork, Lee Maltings, Dyke Parade, Cork T12 R5CP, Ireland

There is an increasing demand among professional and hobby athletes for wearable devices that allow the monitoring of fitness relevant biomarkers. The aim of the H2020-project ELSAH is to develop an electronic smart patch system for wireless monitoring of glucose and lactate in dermal interstitial fluid based on a biofunctionalized microneedle sensor. The metallized microneedles are modified by drop casting novel PEDOT:PSS polymer inks containing direct electron transfer (DET) enzymes and a topping hydrogel layer for mechanical protection and biocompatibility. We investigated the influence of different electrode materials (graphite, gold, platinum) on the enzyme kinetics. For all electrode materials similar values of the Michaelis-Menten constant (Km) were determined with ~25mM for DETGlucose and ~2mM for DETLactate. The PEDOT:PSS/DET inks were optimized with regard to polymer content and enzyme concentration. Higher current differences (for 80mM glucose, [DETGlucose]: 7.2mg/mL) were measured on gold (200nA/mm2) in comparison to platinum (90nA/mm2). Platinum was chosen over gold for the microneedle metallization because of its better processability and lower environmental impact. With the optimized enzyme inks, glucose and lactate could be measured at an interference-free potential of 0V in the physiologically relevant range of 0.1-30mM. Current work focusses on dispensing the conductive enzyme inks with high throughput inkjet printing and other dispensing techniques.

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#11

Bidirectional flow filter: high-purity filtration of biomolecules in low-sample volumes using electrically driven microfluidics

Vesna Bacheva(1,2), Federico Paratore(1,3), Maya B. Dolev(2), Baruch Rofman(2),
Moran Bercovici(2), Govind V. Kaigala(1)

1) IBM Research Europe – Zurich, Switzerland
2) Technion – Israel Institute of Technology, Israel
3) ETH Zürich, Switzerland

BÜHLMANN Laboratories AG developed a unique serological rapid test to assess neutralizing antibodies directed against the novel beta coronavirus SARS-CoV-2. The BÜHLMANN Quantum Blue® SARS-CoV-2 RBD+ Lateral-Flow assay is a qualitative test with high specificity and sensitivity due to the simultaneous detection of antibodies of various isotypes (IgM, IgA, IgG) directed against the SARS-CoV-2 Spike RBD domain. The RBD+ antigen is a highly thermostable, extended RBD that, unlike canonical RBD constructs, does not form disulfide-bridged dimer artefacts in solution.

Therefore, this antigen can be used as capture molecule on the test line (T-line) as well as conjugate on nanoparticles in parallel. In this set-up, bi- or multivalent antibodies that are specific to the SARS-CoV-2 RBD efficiently bridge the antigen on the T-line with antigen conjugated nanoparticles irrespective of their isotype. The antibodies that are recognized by the Quantum Blue® SARS-CoV-2 RBD+ rapid test generally interfere with ACE2 binding of the Spike protein and thus with cell entry of the virus. This rapid test highly correlates with the heterogeneous neutralizing antibody titers of former Covid-19 patients and vaccinated persons and can serve as diagnostic tool to predict their current immune status and susceptibility to infection. The antigen on the control line (C-line) is a synthetic binder pair based on the nanobody scaffold that specifically recognizes the SARS-CoV-2 Spike RBD.  

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#12

A unique rapid test to determine neutralizing antibodies directed against SARS-CoV-2 

Larissa Brosi(1), Benjamin Ricken(1), Lorin Dirscherl(1), Michael Gerspach(1), Cedric Giegelmann(1), Daniele Dolce, Anna Melone(1), Marie-Eve Überschlag(1), Thomas Schuster(1), Frank Bantleon(1) and Christian-B. Gerhold(1)

1) BÜHLMANN Laboratories AG, Baselstr. 55, CH-4124 SchönenbuchSwitzerland 

The analysis of small samples volumes is boosting the field of life and medical science, from basic research on single-cell systems, through point-of-care diagnostics, to forensic analysis. Despite great advances made on analytical techniques such as digital immunoassay, nanopore detection and next-generation sequencing, little progress has been made on low-volume sample preparation technologies, which are key for the success of such analytical techniques.

Recently we developed a low-volume separation method, termed bidirectional flow filter (BFF), which utilizes microscale bidirectional flow, i.e. adjacent streams with velocities in opposite directions, to separate species based on their diffusivities. High diffusivity species introduced into the inlet of a bidirectional flow device experience a net zero velocity and therefore penetrate into the channel only by molecular diffusion, while low diffusivity species are advected downstream by the outgoing flow (Fig. 1a). The BFF can be used as sample-preparation step to selectively separate a mixture of species based on their diffusivity. As proof of concept, we used the BFF to purify genomic DNA from short DNA strands (Fig. 1b-c) and we analyzed the retrieved solution using loop-mediated isothermal amplification (LAMP), to show the presence of the long DNA and the absence of the short DNA.

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#13

Development of electrochemical nitric oxide microsensors for the study of inflammation

Paolo Antonacci, Daniele Zuncheddu, Gaia Rocchitta, Pier Andrea Serra, Mauro Alini, Sibylle Grad and Valentina Basoli.

1) AO Research Institute Davos
2) Department of Biomedical sciences, University of Sassari 

Introduction: During inflammation cells release nitric oxide (NO), a metabolite that can be used as biomarker. Common methods imply the use of sampling and secondary analysis by Griess that assesses the nitrites or by paramagnetic electron resonance (EPR) for direct NO measurement in a solution. However, all these methods cannot provide real time monitoring, limiting the clinical translation. Aim: Investigate the feasibility of using an NO electrochemical sensor optimized for biological inflamed fluids. Material and methods: Platinum wires were modified or not with poly-o-phenylenediamine (p-OPD) applying +700 mV vs an Ag/AgCl reference electrode. This permselective layer prevents interference by factors such as ascorbic (AA) acid and L-Glutamine (Glu), two major oxidants present in biological fluids. The sensors were calibrated with known SNAP concentrations (0 to 100 µM) using a potential at +865 mV, then tested on ex vivo osteochondral plug under inflammatory condition (1 ng/ml IL1b).  

Results: Sensors modified with p-OPD showed lower background noise for AA and none for Glu, that allowed the real time measurement of NO in cells inflamed for 48 hours. P-OPD increased the performance and the reproducibility and real time monitoring in inflamed biological system (Fig.1).  

Discussion and conclusion: The application of NO biological sensors for monitoring in vitro and eventually in vivo inflammation could help to determine the progression/status of widespread pathologies or infections from pathogens in fluids.

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#14

Smart magnetic bead-based immunosensors for SARS-CoV-2 measurement in saliva

Laura Fabiani(1), Vincenzo Mazzaracchio(1), Danila Moscone(1), Silvia Fillo(2), Riccardo De Santis(2), Anella Monte(2), Donatella Amatore(2), Florigio Lista(2), Fabiana Arduini(1),(3*)

 

1) University of Rome “Tor Vergata”, Department of Chemical Science and Technologies, Via della Ricerca Scientifica, 00133 Rome, Italy 

2) Scientific Department, Army Medical Center, 00184 Rome, Italy 

3) SENSE4MED, Via Renato Rascel 30, 00128, Rome, Italy 

Coronavirus disease 2019 (COVID-19) has been recognized as a global pandemic outbreak, opening the most serious socio-economic crisis since Second World War. Different scientific activities have been emerged in this global scenario, including the development of innovative analytical tools to measure nucleic acid, antibodies, and antigens for prompt identification of COVID-19 patients and to evaluate the immune response to the vaccine. The detection of SARS-CoV-2 in saliva remains a challenge for the lack of sufficient sensitivity. To address this issue, we developed the first immunosensor for SARS-CoV-2 detection in saliva (Fabiani, L., et. al. Biosens. Bioelectron., 171, 112686). The electrochemical immunosensor was conceived for Spike (S) protein or N protein detection using magnetic beads as support of immunological chain and secondary antibody with alkaline phosphatase as immunological label (Figure 1). The analytical features of this immunoassay were evaluated in untreated saliva with a detection limit equal to 19 and 8 ng/mL, respectively for S and N protein. Its effectiveness was determined using cultured virus in biosafety level 3 and in saliva clinical samples comparing the data using the nasopharyngeal swab specimens tested with RT-PCR.

To further improve the sustainability of the detection of SARS-CoV-2, herein we present a novel colorimetric immunosensor by combining magnetic beads, wax-printed paper-based 96 well plate and a smartphone-assisted colorimetric detection. 

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#15

Improving the probability of successful in-vitro fertilisation through vaginal microbiome screening using Advanced Technique for Genetic Composition.

Virginia Franco(1), Paulo Refinetti(2),David Baud(3), Milos Stojanov(3), Stephan Morgenthaler(2)

1) YONI Solutions SA, Monthey, Switzerland
2) REM Analytics SA, Monthey, Switzerland
3) Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland 

The relationship between the vaginal microbiome and the probability of a successful in-vitro fertilisation (IVF) have been well documented in the past few years. We propose to use Advanced Testing for Genetic Composition (ATGC) to measure the vaginal microbiome in routine IVF. The goal of our analysis is to develop a diagnostic that could establish a link between vaginal microbiome and the success rates of IVF. ATGC consists in cycling temperature capillary electrophoresis (CTCE) combined with bioinformatics and statistical modelling used to separate DNA molecules based on their physical properties. This technology linked to a specific target will allow us to save time, money and reducing the risks associated with the biopsy currently used. We present the results of a benchmarking analysis against 16S. ATGC shows better results in the latest studies in vaginal infections and with high level of accuracy to screen samples and predict reproductive outcomes. Because of those characteristics already demonstrated, those results are often associated with qualitative and quantitative measurements that allow us to better understand not only the presence of some microbes but also the relation between those based on the level of each one in that specific sample. The model and latest results with ATGC analysis has demonstrated that it is possible to produce effective treatments for Reproductive Medicine. 

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#16

Towards the development of basic technological bricks for a Traumatic Brain Injury diagnostic cartridge

Spyridon Schoinas, Estelle Mairiaux, Ahmad Saidy, Philippe Passeraub

Institute of Industrial Sciences and Technologies, University of Applied Sciences and Arts Western Switzerland (HEPIA/HES-SO Geneva), CH-1202 Geneva, Switzerland

This study focuses on the development of the necessary building blocks for the creation of a Point-Of-Care (POC) diagnostic for the detection of Traumatic Brain Injury (TBI). The development of such a POC diagnostic strives to replace complex, expensive and time-consuming clinical processes for the detection of body fluid biomarkers in the laboratory. This POC diagnostic is based on the combination of reader and consumable (cartridge) concept. Blood separation, plasma transportation on the electrodes and detection of the biomarkers are the most important functions that the technological bricks should enable. Both, Lateral Flow Assay (LFA) and vertical Flow Assay (VFA) concepts provide promising platforms for the accomplishment of these functions. The blood separation is achieved by the integration of a polysulfone filter at the inlet of the cartridge. The plasma transportation function is satisfied by exploiting the inherent capillarity effect of each assay concept. Two detection techniques are explored during this study, namely the electro-impedance spectroscopy (EIS) and the electrochemiluminescence (ECL). Progress in the development of these technological bricks shows promising results. Possible advantages of such a TBI POC diagnostic are early diagnosis, low-cost fabrication, high availability, inherent liquid flow characteristics, compatibility with low volume samples, biocompatibility, biodegradability, direct digitalization of data and decentralized testing.

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#17

Fast, accurate and quantitative screening of antibiotic resistant S. Aureus using Advanced Testing for Genetic Composition (ATGC)

Mariya Skvorstova(1), Patricia Refintti(2), Stephan Morgenthaler(1), Shawna McCallin(3), Paulo Refinetti(1)

1) REM Analytics SA, Rte. De l’Ile-au-Bois 1a, Monthey, Switzerland
2) University College of London Hospital,
3) Universitätsklinik Balgrist Forchstrasse 340,  Zürich, Switzerland 

Several infections can contain more strains of micro-organisms. State of the art is bacterial culture, and quantifying the amount of antibiotic resistant and susceptible bacteria requires a double culture process. These processes are slow, expensive, and often result in a therapy being prescribed BEFORE the results are available.  

Advanced Testing for Genetic Composition (ATGC) is a technology that incorporates bio-informatics, with Cycling temperature capillary electrophoresis (CTCE). Specialized assays can be designed for a variety of pathogenic groups, and results can be produced within 2hATGC is here benchmarked against culture methods.  

Methods: 2 strains of Staphylococcus aureus have been selected: mu50 which is Vancomycin resistant, and Newman, which is not. Mixed cultures of Newman and mu50 were produced and grown in different vancomycin concentrations and repeatedly sampled. 

 Samples were then split into 2 agar plate, one with a high concentration of Vancomycin, and one without. The relative abundance of mu50 in each sample could be inferred from the relative CFU count.  

Using ATGC, an assay was designed to differentiate mu50 from Newman. The same samples were processed by ATGC: a combination of PCR, CTCE, and bio-informatics.  

Results: There was a strong correlation between the CFU count and ATGC results. Variability between technical replicates of ATGC was less than 5%, and 10% for CFU countThese results support the further development of ATGC for point-of-care diagnostics.   

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#18

Tools Enabling EEG Signals Analysis and Extraction of Depth of Anesthesia Index in Veterinary Practice

Yoann Flck(1), Alena Simalatsar(1), Alessandro Mirra(2), Darren Hight(3), Olivier Levionnois(2)

1) Industrial Systems, HES-SO Valais-Wallis, Sion, Switzerland
2) Vetsuisse Faculty, University of Bern, Switzerland
3) Inselspital, Bern, Switzerland 

The provision of correct depth of anaesthesia (DoA) is mandatory not only to veterinary patients (e.g., dogs, cats, horses etc.) but also for pigs undergoing experimental procedures, in order to ensure both their welfare and the repeatability of the results obtained. Inhalant anaesthesia is often avoided in veterinary practice due to the imposed technical constrains, while injectable drugs (e.g., propofol, an anaesthetic widely used also for humans) are preferred instead. However, there is a lack of technologies to guide injectable anaesthetic administration in animals. Therefore, injectable drugs are provided without other means for individualized titration than subjective clinical observation or human-based depth of anaesthesia monitoring strategies 

Anaesthesia individualization can be performed based on objective point-of-care (POC) measures of DoA like electroencephalogram (EEG)-based bispectral index (BIS) and Patient State Index (PSI). However, the algorithms computing these DoA indices are proprietary and developed for humans, and thus, cannot be applied or adapted to veterinary practice. Therefore, there is a need to develop novel EEG based DoA index for pigs. 

We have developed Matlab tools enabling EEG signal analysis collected from pigs undergoing general anaesthesia with propofol. In particular, we have: 1) developed signal processing algorithms to extract features suitable for construction of induced DoA indexe.g.such as burst-suppression ratio’s (BSR), spectral edge frequency (SEF), power spectrum for various frequency bands, etc.; 2) developed graphical user interface facilitating comprehensive analysis of extracted features; 3) constructed first generation DoA index for pigs. 

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#19

CVD graphene synthesis,fabrication& characterization for applications

Dr. Kishan Thodkar

Micro& Nanosystems, Dept. of Mechanical & Process engineering, ETH Zurich,Tannenstrasse 3, Zurich 8057, Switzerland
Email: kishant@ethz.ch

Single layer graphene(SLG)films offerseveral featuressuch asi) a wide range of noncovalent molecular functionalization[1], ii) high field effect mobility& current density(~6x103cm2/Vs, 300 K)[2, 3], iii) transparency (~97% to visible light), iv) flexibility & high mechanical strength (~1 TPa).Using chemical vapor deposition(CVD), massproduction of graphene films for industrial applications is achievable today. Current progress in standardizationof graphene & 2D material quality is encouraging towards industrial applications using graphene filmssuch as lowcost diagnostic kits.[4]In this poster, we present the progress in CVD graphene synthesis and film quality characterization(see: figure 1)using Raman spectroscopy. Second, functionalization of the graphene surfaceusing two types of molecular linkersis performedto assess potential applications of graphene films. Third,a novel approach forCVD heterostructure formation using CVD graphene & CVD hexagonal Boron Nitride (hBN) is presented. Such heterostructure are explored for the development ofhigh performance graphene device applications[5].

References
[1] K. Thodkar, P.-A. Cazade, F. Bergmann, E. Lopez-Calle, D. Thompson, D. Heindl, ACS Applied Materials & Interfaces. 202113, 9134, DOI: 10.1021/acsami.0c18485.

[2] K. Thodkar, E. M. Abbassi, F. Lüönd, F. Overney, C. Schönenberger, B. Jeanneret, M. Calame, physica status solidi (RRL) –Rapid Research Letters. 201610, 807, DOI: 10.1002/pssr.201600211.

[3]K. Thodkar, D. Thompson, F. Lüönd, L. Moser, F. Overney, L. Marot, C. Schönenberger, B. Jeanneret, M. Calame, ACS Applied Materials & Interfaces. 20179, 25014, DOI: 10.1021/acsami.7b05143.

[4]ISO, ISO/TS 21356-1:2021, https://www.iso.org/standard/70757.html.

[5]Novel, high-throughput compatible dry transfer approach to enable high performance, suspended CVD 2D material heterostructure electronic devices and their applications, dryhetero, 101025295, Horizon 2020, MSCA-Individual Fellowship 2020.

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#20

Near-infrared photoluminescent biosensors based on single-walled carbon nanotubes

Sayyed Hashem Sajjadi, Alice J. Gillen, Shang-Jung Wu, Melania Reggente, Alessandra Antonucci,  Niloufar Sharif, Daniel Morales, Ardemis A. Boghossian

École Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland 

Single-walled carbon nanotubes (SWCNTs) emit near-infrared (NIR) fluorescence that is ideal for continuous and long-term in vivo optical monitoring. Spanning the tissue transparency window, the NIR SWCNT fluorescence can optically penetrate biological tissue for deep-tissue imaging and optical sensingSWCNTs are often functionalized with single stranded DNA (ssDNA) to yield sensors that are biocompatible, responsive, and selectiveOne such ssDNA-SWCNT sensor has been developed to detect dopamine, a neurotransmitter that is linked to the pathology of neurological diseases like Alzheimer’s and Parkinson’s disease. However, the competitive responsivity of this ssDNA-SWCNT dopamine sensor to cations such as Ca2+ has limited their use for in vitro and in vivo measurements that require differentiation in signaling responses between the dopamine and fluctuating cation concentrations. Furthermore, the low brightness of these ssDNA-wrapped sensors restricts the depth at which such sensors can be implanted in the tissue. 

In this work, we bioengineer the DNA wrapping by incorporating locked nucleic acid (LNA) bases that show a selective turn-on fluorescence response to dopamine in the presence of varying cation concentrations (Fig 1a-b). Furthermore, we demonstrate the fluorescence enhancement of ssDNA-wrapped SWCNTs through the incorporation of biocompatible graphene quantum dots (GQDs). The GQDs were shown to significantly increase the fluorescence efficiency of ssDNA-SWCNTs (Fig 1 c)even enabling the single-molecule imaging of individual SWCNTs using NIR confocal microscopy (Fig 1d). These advancements provide a promising basis for engineering not only the selectivity but also the brightness of NIR sensors for biomedical applications.

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#21

Sound-induced cell assembly to engineer vascularised tissues – towards patient specific drug evaluation 

Anne Géraldine Guex(1), Mauro Alini(1), Tiziano Serra(1) 

1) AO Research Institute Davos, Switzerland 

Prior to point of care diagnostics and concomitant treatments, efforts in basic research focusing on drug development are urgently needed. In the scope of personalised medicine, in vitro models with patient-specific cells are particularly interesting to evaluate new treatment-options. As a first step towards this, we develop vascular structures within hydrogels which will ultimately permit to engineer vascularised tissues to assess local or systemic drug administration.  

Our approach uses acoustic waves that create standing Faraday waves at the hydrogel-air interface, thereby projecting cells into defined patterns by hydrodynamic forces. Specific in this setting is the use of low frequency (< 100 Hz) sound waves, enabling cell manipulation within mili or centimetre-scaled labware. A cell suspension of human mesenchymal stem cells and endothelial cells within a hydrogel was patterned into concentric rings. Over time, endothelial cells assembled into vascular structures. Lumen formation and sprouting is currently evaluated based on immunofluorescent imaging. In future studies, pro- and anti- angiogenic drugs will be assessed and the model will be complemented with tissue-specific cells. In summary, tight control over pattern formation, combined with a large portfolio of application-tailored hydrogels render sound-induced cell assembly an extremely versatile method to generate in vitro models of high precision for pharmaceutical evaluation.     

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#22

Point-of-Care Tests for Preeclampsia

Mathias Wipf(1), Christopher S. Wood(2), Mark Fretz(3), Daniel Gygax(2)

1) MOMM Diagnostics GmbH, Hochbergerstrasse 60C, 4057 Basel, Switzerland
2) FHNW School of Life Sciences, Hofackerstr. 30, 4132 Muttenz, Switzerland
3) CSEM Center Alpnach, Untere Gründlistrasse 1, 6055 Alpnach Dorf, Switzerland 

MOMM Diagnostics is developing a fast and precise point of care test for preeclampsia – a dangerous pregnancy condition. Our technology will assist doctors on-site to save the lives of mothers and babies. MOMM Diagnostics’ novel pointofcare technology allows the simultaneous quantification of two low-abundant biomarkers from a single drop of the mother’s blood. MOMM’s rapid preeclampsia test aims at reliable and early-stage molecular diagnosis of PE during doctors’ visits, using low-cost single-use cartridges and a hand-held reader. 

Our technology is based on enzyme-linked lateral flow immunoassays (ELLFIA), for signal amplification, in combination with a quantitative electrochemical readout, by integration of low-cost ion-sensitive electrodes in single-use test cartridges. The approach enables rapid biomarker quantification down to sub-picomolar concentrations and opens previously laboratory-based diagnostic tests to point- of- need and self-testing. 

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TERMS AND CONDITIONS OF POSTER SESSION FOR THE SWISS SYMPOSIUM IN POINT-OF-CARE DIAGNOSTICS 2021:

Successfully submitted abstract will be acknowledged via an e-mail with a poster number, which should be quoted in all correspondence. Allow at least 48 hours for your receipt to be returned to you.
Once the abstracts is accepted, at least one of the authors must register for and present at the symposium. Abstracts of all accepted contributions will be included within the abstract book, which will be distributed to all registered conference participants.