This is the time when innovation is crucial Time setter Janice Odijk is scientist workforce development such a wide variety of research is conducted Janice is a scientist in workforce development at TNO She works on innovations for organisations in the security domain ‘I work on knowledge development and learning technology to support security professionals and organisations with complex staffing issues such as sustainable employability and the development of unique skills I do this in a multidisciplinary team with educational experts data scientists and even colleagues with a background in construction engineering I myself am an organisational psychologist It is wonderful that everyone approaches challenges from a different perspective Janice came into contact with TNO through her previous job I was tasked with researching an innovation for objective recruitment and selection I conducted an experiment to test whether it truly promotes equal opportunities in job applications This impactful innovation led me to work at TNO.’ 'It is wonderful that everyone approaches challenges from a different perspective Making the application process more objective is a subject Janice focuses on extensively and provides training in ‘It is about looking at what really matters on the job – not gender ethnicity or hobbies – but what someone can do and how to optimally match person and position This ensures people end up in positions where they can use their strengths and are less likely to leave the organisation.’ She emphasises the importance of diverse perspectives within an organisation they quickly think of demographic checkboxes: gender but that is just one side of the story,’ says Janice ‘Backgrounds and experiences provide valuable perspectives on the work My Cape Verdean background and experiences as a woman and researcher mean I look at issues slightly differently than colleagues These differences in perspective are valuable especially for organisations seeking to innovate.’ Janice believes diversity begins with inclusive leadership ‘You cannot utilise diversity if you are not open to different ways of thinking and doing,’ she explains Everyone must have a fair chance to be seen and heard at work.’ 'You cannot utilise diversity if you are not open to different ways of thinking and doing.' it was important for me to be supported by women in positions I aspired to It gave me the feeling: 'I can do that too' That has made the difference for me.’ Janice emphasises the importance of self-confidence and discovering your strengths and surround yourself with people who stimulate that in you,’ she says And it is incredibly important to have positive role models in your life TNO believes in the power of women and that everyone should have the same opportunities to participate and grow We are proud to showcase some of our talented women in technology and leadership on International Women's Day To show girls and women that they are welcome in these roles This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page Metrics details Quantification of diamine oxidase (DAO) concentrations in serum has been proposed as an adjunctive diagnostic modality for the evaluation of histamine intolerance (HIT) Limited empirical data exist concerning the influence of dietary patterns on DAO levels In the context of a prospective study employing a crossover design 18 individuals diagnosed with HIT were randomized to initiate either a low histamine diet (LHD) or a conventional mixed diet (MXD) Serum DAO concentrations were measured at the commencement of the study and following each dietary phase A control group underwent analogous DAO assessments without imposition of dietary constraints During the time when a diet restricted in histamine was implemented noticeable differences in changes in DAO levels did not become apparent when compared to the changes observed during the mixed (MXD) phase 10 of the 18 patients exhibited elevated DAO values subsequent to the LHD regimen while the remaining eight displayed either reduced or unchanging DAO levels The prevalence of elevated DAO levels in the LHD group did not differ significantly from that observed in the control group during the MXD phase patients reported a significant reduction in gastrointestinal and cutaneous symptoms This prospective investigation underscores the enduring utility of a histamine-restricted diet coupled with structured dietary reintroduction as an efficacious diagnostic approach for individuals presenting with suspected food-related histamine hypersensitivity the measurement of DAO levels appears to furnish only a limited capacity to discern dietary-induced fluctuations the dynamics of DAO alteration do not appear to exhibit a discernible association with specific dietary patterns a finding consistent across both patient and control groups More data is needed to understand how DAO activity levels are affected by an ordinary mixed diet and a diet with low histamine content The aim of this study was to assess DAO activity measured in serum in relation to diet (mixed compared to a low histamine diet) and to evaluate self-assessed food-related symptoms associated with histamine hypersensitivity during the dietary intervention period The exclusion criteria for study invitation included adherence to a vegan or incompatible diet with the study protocol and diagnosed inflammatory or systemic rheumatologic disease Patients were randomly assigned to undergo two different 3-week dietary interventions: a low histamine diet (LHD) and a regular mixed diet (MXD) Blood samples were collected at three specific time points for measuring the levels of diamine oxidase (DAO) in both groups The first sampling (DAO 1) occurred before the dietary interventions started the second after three weeks of adhering to the mixed diet (DAO 2) and the third after three weeks of switching between the low histamine and mixed diets (DAO 3) Throughout the entire six-week dietary intervention patients diligently recorded their symptoms in designated diaries The control group did not undergo any dietary interventions but blood samples for DAO quantification were collected at the same three-time points as in the patient group with 0 indicating no symptoms and 3 indicating severe symptoms The recorded symptom categories included mainly gastrointestinal pain (as well as altered stool consistency such as loose stool or diarrhoea sporadically in a few individuals) Participants were allowed to manually add any additional symptoms not covered by the symptom diary in open questions consisting of 9 subjects without any reported histamine-related food hypersensitivity underwent the same procedure with analysis of the DAO levels simultaneously as the patient group during the same 3-weeks intervals during the dietary interventions and were asked to complete the same questionnaires No dietary restrictions were imposed on the control group and they were instructed to maintain their regular diet during the entire study period The measurement of DAO levels in the samples was performed using a commercially available kit (DAO-REA Sciotec, HS 421-37; Tulln an der Donau, Austria) according to the manufacturer’s instructions [28] According to levels defined by the assay manufacturer values < 3 U/mL were considered to be distinctively decreased levels of DAO 3–10 U/mL were considered to be slightly decreased and ≥10 U/mL was considered as normal levels Statistical analyses were conducted using SAS 9.4 from SAS Institute Inc. median and minimum-maximum values are presented DAO values were log-transformed to reduce skewness Categorical variables are expressed as numbers Differences between groups were assessed using Friedman’s test and GLM/Mixed models Symptom analysis and corresponding box plots were generated using R Studio Version 1.3.959 The analysis was based on aggregated symptom data where daily values for each symptom (stomach pain headache) were summed for each diet (low histamine diet and mixed diet) to yield a single value per diet per individual Daily data values for the outcome “stools” were similarly summed for each symptom and diet and comparisons were made using a paired t-test Statistical significance was set at p < 0.05 for all comparisons The study was approved by the Regional Ethics Board in Gothenburg During the observational period spanning from 2018 to 2022 a total of 27 patients met the eligibility criteria for participation 20 patients consented to participate in the study two patients withdrew from the study for distinct reasons: one due to intolerable adverse reactions encountered during the mixed diet (MXD) phase and another due to unrelated issues a subgroup of 12 out of 18 individuals presented with atopic conditions encompassing six cases of allergic rhinoconjunctivitis three cases featured optimally managed asthma while the remaining six patients exhibited no concurrent atopic conditions none of the recruited patients had pre-existing gastrointestinal ailments or systemic conditions including mast cell disorders or rheumatic disorders none of the female patients in the study were pregnant Analysis of the diamine oxidase (DAO) values in patients during three phases of a crossover dietary intervention - baseline Control group: Analysis of the DAO values in a control group without dietary restrictions No significant fluctuations or differences in DAO levels were observed either between patients and the control group or among the different dietary phases within the patient group (p > 0.05) This assessment was performed using the non-parametric Friedman’s ANOVA test Symptoms from the gastrointestinal tract (mpain) and skin (mskin) were found significant higher (p < 0.05) during the MXD compared to LHD Aggregated symptom scores are defined whereas daily symptom values for an individual are added for a particular symptom (gastrointestinal pain headache) and a diet (LHD respectively MXD) to provide one single aggregate value for that symptom per individual and per diet no significant difference in DAO activity was observed based on the type of diet Baseline DAO values exhibited a wide distribution with approximately half of the participants having values below the suggested cut-off of 10 U/ml Baseline DAO values in the control group did not differ significantly from those in the patient group indicating that DAO cannot be utilized as a diagnostic tool no increase in the occurrence of headaches or other neurological symptoms was observed when shifting from LHD to MXD with the content of foods rich in histamine It is important to note that the current commercial technique for analyzing Diamine Oxidase (DAO) from Sciotec (DAO-REA 3H) employs putrescine as a substrate whether putrescine or the native substrate histamine the Sciotec method is the only available approach for determining DAO levels it may pose a challenge to ascertain whether the determination of DAO levels would exhibit variations when utilizing a method that exclusively employs the original histamine substrate This study stands out as one of the few prospective studies utilizing a crossover design with continuous diet monitoring conducted by a dietitian to ensure adherence and collect reliable data The study’s limitations include small sample size and challenges in participant recruitment particularly exacerbated during the COVID-19 pandemic when adhering to a crossover diet proved demanding a few participants withdrew due to their reluctance to revert to the standard mixed diet after experiencing significant symptom alleviation through the histamine-reduced diet it is important to highlight that these patients maintained close contact with the study coordinator throughout various diet periods ensuring meticulous adherence to the diverse diets tested during the study duration it is desirable to subject the control group to the same dietary intervention as the patient group participants without any food-related issues showed limited motivation this cross-sectional study demonstrates that the histamine-reduced diet remains the only reliable and eligible diagnostic tool for patients with suspected non-IgE mediated food-related histamine intolerance while the analysis of the DAO levels showed to be inconclusive as a diagnostic tool Changes in DAO did not seem to be related to the type of diet in patients No variation in the DAO levels could be demonstrated in the control group despite a constant diet larger prospective studies with more motivated participants are necessary to further explore the potential utility of measuring DAO levels in this specific patient population The data that supports the findings of this study are available upon reasonable request from the corresponding author (JvO) The data are not publicly available due to local legislation related to data derived from patients´ medical records Scientific Opinion on risk based control of biogenic amine formation in fermented foods Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization Histamine food poisonings: A systematic review and meta-analysis Tuck CJ, Biesiekierski JR, Schmid-Grendelmeier P, Pohl D. Food Intolerances. Nutrients 2019; 11. https://doi.org/10.3390/nu11071684 Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Histamine Intolerance: The Current State of the Art. Biomolecules 2020; 10. https://doi.org/10.3390/biom10081181 Scientific opinion on risk based control of biogenic amine formation in fermented foods. The rate of histamine degradation by diamine oxidase is compromised by other biogenic amines German guideline for the management of adverse reactions to ingested histamine: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) the German Society for Pediatric Allergology and Environmental Medicine (GPA) the German Association of Allergologists (AeDA) and the Swiss Society for Allergology and Immunology (SGAI) Guideline on management of suspected adverse reactions to ingested histamine: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) the Society for Pediatric Allergology and Environmental Medicine (GPA) the Medical Association of German Allergologists (AeDA) as well as the Swiss Society for Allergology and Immunology (SGAI) and the Austrian Society for Allergology and Immunology (ÖGAI) Serum diamine oxidase activity as a diagnostic test for histamine intolerance Cucca V, Ramirez GA, Pignatti P, Asperti C, Russo M, Della-Torre E, et al. Basal Serum Diamine Oxidase levels as a biomarker of histamine intolerance: A retrospective cohort study. Nutrients 2022; 14. https://doi.org/10.3390/nu14071513 Serum diamine oxidase activity in patients with histamine intolerance Arih K, Đorđević N, Košnik M, Rijavec M. Evaluation of Serum Diamine Oxidase as a diagnostic test for histamine intolerance. Nutrients 2023; 15. https://doi.org/10.3390/nu15194246 Histamine intolerance in patients with chronic spontaneous urticaria Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema Vassilopoulou E, Konstantinou GN, Dimitriou A, Manios Y, Koumbi L, Papadopoulos NG. The impact of food histamine intake on asthma activity: a pilot study. Nutrients 2020; 12. https://doi.org/10.1038/sj.ejcn.1600911 A popular myth - low-histamine diet improves chronic spontaneous urticaria - fact or fiction Histamine plasma levels and elimination diet in chronic idiopathic urticaria van Odijk J, Rentzos G. Is DAO in serum affected by food challenge with a histamine-rich meal? J Allergy Clin Immunol: Glob. 2023; 2. https://doi.org/10.1016/j.jacig.2023.100097 Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance Intestinal allergic inflammation in birch pollen allergic patients in relation to pollen season IgE sensitization profile and gastrointestinal symptoms Measurements of eosinophil activation before and after food challenges in adults with food hypersensitivity Daily variations of serum diamine oxidase and the influence of H1 and H2 blockers: a critical approach to routine diamine oxidase assessment Inhibition of human and canine diamine oxidase by drugs used in an intensive care unit: relevance for clinical side effects van Odijk J, Weisheit A, Arvidsson M, Miron N, Nwaru B, Ekerljung L. The use of DAO as a marker for histamine intolerance: measurements and determinants in a large random population-based survey. Nutrients 2023; 15. https://doi.org/10.3390/nu15132887 Histamine intolerance-like symptoms in healthy volunteers after oral provocation with liquid histamine Treatment of Atopic Dermatitis with a low-Histamine diet A Histamine-free diet is helpful for treatment of adult patients with chronic spontaneous Urticaria Concomitant prevalence of low serum diamine oxidase activity and carbohydrate malabsorption Histamine intolerance and dietary management: A complete review Download references We are grateful to the persons who participated in this study This work was funded by The Health care committee Region Västra Götaland (reference number: 853201) Open access funding provided by University of Gothenburg Department of Internal Medicine and Clinical Nutrition Department of Respiratory Medicine and Allergology and Linda Ekerljung (LE) designed the study JvO and Adina Weisheit (AW) collected the data JVO and GR analyzed the data and wrote the paper All authors have read and agreed to the published version of the paper The authors declared no competing interests The study was approved by the regional ethics board in Gothenburg Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41430-024-01448-2 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Collaboration will be much in evidence at Nor-Shipping 2023 with Ocean Hyway Cluster and Maritime Cleantech jointly presenting a maritime hydrogen conference The second Nor-Shipping Hydrogen Conference will take place in Hall 2A – Studio N from 12:00-16:00 and will feature an introduction by Ocean Hyway Cluster communications advisor Siri Odijk Solbakken and Maritime CleanTech project co-ordinator Tonje Hovland “We will get the audience up to date on new developments EU regulations and the progress that is being made to scale up the (ammonia and hydrogen) projects,” said Ms Hovland adding the debates will be “short and sharp” with a process to allow the audience to “ask their toughest questions.” The conference will be divided into two parts: the global perspective and scaling up maritime market demand The first element covering market mechanisms and regulations is titled ‘Carrot and Stick’ and features participation from principals in the Norwegian hydrogen and ammonia sectors including Yara Clean Ammonia president Magnus Krogh Ankarstrand and Norwegian Hydrogen chief executive Jens Berge The second section involves presentations from the maritime sector including Amon Maritime founder and chief executive André Risholm and Flagships/Sogestran project engineer Mathieu Longueville The presentations will be followed by a debate moderated by Riviera Maritime Media executive editor and head of business relations Edwin Lampert The event is topped off by a roof-top event at a nearby venue, but hurry, there are a limited amount of tickets available Sign up for Riviera’s series of technical and operational webinars and conferences in 2023: The dates displayed for an article provide information on when various publication milestones were reached at the journal that has published the article activities on preceding journals at which the article was previously under consideration are not shown (for instance submission All content on this site: Copyright © 2025 Elsevier B.V. the participation of females in clinical trials has been underrepresented1 in the period of 1977-1993 most woman of “childbearing potential” where banned from participating in clinical studies2 This underrepresentation causes large gaps in knowledge about gender specific medication LiGalli is a company that is: on a mission to revolutionize women’s health care LiGalli is trying to develop a smart vaginal ring for intra-vaginal sensing and is collaborating with BIOS on this subject The day-by-day research for the LiGalli project at the UTwente is run by two post-doctoral researchers Sevil Sahin is responsible for the sensing Jasper Lozeman is responsible for the sampling and microfabrication The project is further managed by two PI’s namely professor Loes Segerink and professor Mathieu Odijk This specific master assignment will be under the supervision of Jasper Lozeman and will focus on the microfluidics involved in the chip The projects consist of several components such as a sampling chamber and liquid storage The microfluidics will need to connect all the different components together The footprint of the microfluidics needs to be small enough to fit in the LiGalli ring a commercially viable device needs to be fabricated This brings with it an additional challenge; the design should be relatively easy to be fabricated and mass produce This means minimal use of cleanroom technology or any exotic materials For this assignment we look for a student that is interested in microfabrication and microfluidics Since the project is in collaboration with several companies the student should be willing to work on projects with a commercial application in mind Are you interested and do you want to know more Dr. Jasper Lozeman j.j.a.lozeman@utwente.nl Prof. dr. ir. Mathieu Odijkm.odijk@utwente.nl Enrollment of female participants in United States drug and device phase 1–3 clinical trials between 2016 and 2019 Inclusion of Women in Clinical Trials: A Historical Overview of Scientific Ethical and Legal Issues Metrics details Microfluidic systems enable automated and highly parallelized cell culture with low volumes and defined liquid dosing systems typically integrate all functions into a single monolithic device as a “one size fits all” solution this approach limits the end users’ (re)design flexibility and complicates the addition of new functions to the system we propose and demonstrate a modular and standardized plug-and-play fluidic circuit board (FCB) for operating microfluidic building blocks (MFBBs) whereby both the FCB and the MFBBs contain integrated valves A single FCB can parallelize up to three MFBBs of the same design or operate MFBBs with entirely different architectures The operation of the MFBBs through the FCB is fully automated and does not incur the cost of an extra external footprint We use this modular platform to control three microfluidic large-scale integration (mLSI) MFBBs each of which features 64 microchambers suitable for cell culturing with high spatiotemporal control We show as a proof of principle that we can culture human umbilical vein endothelial cells (HUVECs) for multiple days in the chambers of this MFBB we also use the same FCB to control an MFBB for liquid dosing with a high dynamic range Our results demonstrate that MFBBs with different designs can be controlled and combined on a single FCB Our novel modular approach to operating an automated microfluidic system for parallelized cell culture will enable greater experimental flexibility and facilitate the cooperation of different chips from different labs an essential factor to take into account when designing massively parallelized microfluidic cell culture systems such highly integrated chips are challenging to develop and set up custom software for chip-specific operation and a highly optimized operating protocol flexible alterations to the design of these monolithic chips are not easily realizable when required by the experimental question To address this challenge in maintaining design flexibility while setting up a highly parallel mLSI cell culture system we propose a modular approach to create a versatile system based on a library of standardized components we extend our FCB MFBB technology by developing the first FCB that contains an active function: an MFBB enabler We use this FCB to operate mLSI MFBBs both in parallel and selectively and hereby present the first modular plug-and-play system for mLSI chips we demonstrate the versatility of the FCB by using the same FCB to control two MFBBs which have entirely different architectures we show that the FCB MFBB enabler can “save” the states of the valves in the mLSI MFBB This feature allows us to combine both the dosing and the mLSI MFBB into a single system while operating both MFBBs using a shared set of control lines via the FCB we show as a proof of principle that we can culture human umbilical vein endothelial cells (HUVECs) in the chambers of an unmounted mLSI MFBB as a first step toward applying this modular technology to create automated and highly parallelized yet versatile cell culture systems The channels in the flow layer are shown in blue while the channels in the control layer are shown in green c Schematic side view of a valve in normally open “push-up” configuration d Brightfield micrograph illustrating the multiplexing principle for the first four chambers e The brightfield micrograph on the left shows the bypass channel blocked by valves whereby the flow is directed into the chambers The right micrograph shows the chambers blocked by valves purging the channels without mixing with the chamber content The reason for the minor adjustments was to improve the MFBB for cell culture This MFBB applies the concept of PWM to accomplish microfluidic dosing so that concentration profiles with a wide range of mixing ratios (i.e. high dynamic range over 1–2 orders of magnitude) within a short time period (tens of seconds) can be generated a Schematic diagram of the MFBB working principle b Schematic side view of the integrated valves c Realistic side view of the MFBB showing all four layers the hydraulic resistors (layer ①) and the top part of the valves (layer ②) containing the control channels (layer ③) and the bottom part of the valves (layer ④) and R (Pa s m−3) is the hydraulic resistance and R3 allow for a high dynamic range in the dosed volume per time unit a high dynamic range in concentration is achieved when the dosed volume from inlet 1 is combined with fluid from inlet 2 (or vice versa) different concentration profiles can be generated by combining flow from the two fluids that are routed through two different hydraulic resistors the number of concentration profiles is limited by the number of resistor combinations the valves are opened with defined pulse widths to modulate the fluid volume from each inlet thereby generating many different concentration profiles the mixture is then directed to one of the outlets and homogenized by Taylor dispersion in the connected tubing One dosing MFBB can output fluid mixtures to up to three subsequent MFBBs (one per outlet) which then receive the fluid mixture as an input the purge inlet serves to clear the channels (and optionally the tubing) with a neutral fluid a Schematic side view of the FCB and three MFBBs The MFBB control channels (green) are operated via the FCB The FCB control channels (orange) can block pressure transmission to an MFBB If the FCB valve of an MFBB is closed (open) the MFBB is disabled (enabled) or OFF (ON) Each of the 13 MFBB control channels branches off from a common inlet to 3 MFBB ports Each set of channels is controlled by a set of FCB valves (purple) a Fabricated parts for the platform assembly (ii) clamp (3 cm × 3 cm) for the dosing MFBB (iv) clamp (3 cm × 6 cm) for the mLSI MFBB b Fully assembled platform with three mLSI MFBBs filled with food coloring gradients The assembly of the MFBBs on the FCB is simple and depends on screwing nuts and bolts into the clamps that hold the MFBBs in place thus creating leak-proof interfaces between the inlets of the MFBBs and the outlets of the FCB via O-rings the O-ring pockets are marginally too deep to reliably give sufficient O-ring compression at all interconnects every time an MFBB is mounted Due to the minimal compression and close proximity of the O-rings even slight variations in O-ring thickness can lead to a thinner O-ring not sealing sufficiently when it is placed next to thicker O-rings the water in the MFBB control channel leaks out at the O-ring and the valves in the MFBB do not close fully we succeeded in mounting three mLSI MFBBs leak-free by rearranging the O-rings based on their thickness and carefully tightening the clamp We expect that the reliability of O-ring seals can be greatly improved in the next FCB generation by designing for at least 15% compression instead of 10% which will also shorten the time required for platform assembly a A flow channel in an MFBB was opened and the flow through the channel was measured the flow was stopped by pressurizing the control channel in the MFBB through the FCB and the pressure to the FCB for the MFBB control channels was released b Schematic representation of enabling (ON) and disabling (OFF) the MFBB c Video frames of sequential MFBB operation Although the total number of independently addressable chambers is not as high as in monolithic systems previously presented in the literature the modular approach gives the user more freedom in tailoring the system to experimental requirements if the aim is to perform preliminary testing to identify a promising concentration range for the desired efficacy of a new compound a system with hundreds of chambers is unnecessary the user can choose between using only one or all three of the mLSI MFBBs to suit their aim In an analogy to standard cell culture in microtiter plates this system can be considered as offering the ability to switch between microtiter plates with a Dynamic range characterization of the dosing MFBB in terms of flow rate through the three hydraulic resistors at a pump pressure of 300 mbar b Schematic of the dosing MFBB and the mLSI MFBB operated via the FCB the dosing MFBB can be used to fill the chambers of the mLSI MFBB c Video frames showing the two MFBBs on the FCB and connected to each other with tubing d Chambers of the mLSI MFBB filled with red or blue food coloring (which were selected in the dosing MFBB) or gradients generated by a long pulse of one food coloring followed by a long pulse of the other food coloring (chambers 33–64) The close-up view of chambers 33–64 consists of stitched brightfield micrographs Chambers 33–61 are filled with a food coloring gradient generated by a long red pulse following a long blue pulse (the chambers were filled in reverse order) Fully purging the tubing between the two MFBBs of its content (approximately 8 µL) took approximately 7.5 min The comparatively large dead volume of the tubing is a drawback of the current FCB we will connect the MFBBs via channels in the FCB which will allow us to reduce the dead volume to approximately 1.5 µL (80% reduction) This connection will decrease the total filling time and save reagents The mLSI MFBB is designed to be suitable for multiplexed cell culture HUVECs were cultured in the chambers of an unmounted mLSI MFBB the glass slide of the MFBB did not have through-holes; instead the control channel inlets were punched through the PDMS from the top The MFBB was prepared for cell seeding by coating the flow channels with PLL-PEG (100 µg/mL in phosphate-buffered saline (PBS)) to reduce cell adhesion and coating the chambers with collagen I (0.1 mg/mL in PBS) to promote cell adhesion After the cells were seeded in the chambers a program was set to exchange the cell medium chamber by chamber every 3 h a Live-cell fluorescence images (one image per four chambers) showing an overview of all the chambers after 3 days of culturing GFP-expressing HUVECs b Live-cell fluorescence image of GFP-expressing HUVECs in chambers 6 and 7 c Fluorescence image of fixed HUVECs with the cell F-actin and nuclei stained with ActinRed and NucBlue d HUVECs after seeding and subsequent monolayer formation The cells were seeded at a high cell density (i) and confluent on day 1 (ii) The monolayer was still intact on day 3 (iii) but began to deteriorate on day 4 (iv) the medium in the supply vial was replaced The cells showed signs of recovery on day 5 (v) as the monolayer started to reform The red dots in (iv) and (v) mark the cells counted in the region of interest e Cells in ten chambers were counted in regions where the monolayer had deteriorated on day 4 (98 h) and after 16 h of recovery (114 h) The black dots represent the mean cell count and the error bars represent the standard deviation The cell number increased by an average of 33% in these areas the monolayer became disrupted with the formation of large gaps It was hypothesized that the cell stress was due to degradation of the medium in the vial connected to the MFBB inlet the vial was replaced with one containing fresh medium the cells showed signs of recovery as they reformed the monolayer whereby the black dots and error bars represent the means and standard deviations the cell population in these areas increased by 33 ± 17% within 16 h The described platform consisting of the FCB and MFBBs is By integrating an MFBB enabler into the FCB we can operate up to three of the same MFBBs in parallel or operate and combine different MFBBs with different operation protocols The standardized interface with clamps and O-ring connections allows for different MFBBs fabricated by different methods to be combined in a single system as demonstrated with our micro-milled dosing MFBB and soft lithography-based mLSI MFBB Our modular approach toward creating automated highly parallelized cell culturing systems will give the end-users more flexibility in several aspects this system provides flexibility in redesigning the microfluidic chips since only the layers in the MFBB are affected As long as the new MFBB retains the same interface and a standardized format it can be operated via the same reusable FCB it becomes possible to run different experiments on different chips (e.g. with design criteria tailored to different cell types or cell constructs) simultaneously without having to use multiple pneumatic control setups for the mLSI chips it is possible to exchange MFBBs on the FCB to adjust the system to a new application we demonstrated the technical functionality of our system we are working on the development of further MFBBs and on using the mLSI MFBB for stem cell differentiation we plan to improve our platform by making it more broadly compatible with automated imaging systems special microscope objectives with long working distances are needed to image through the FCB We plan to solve this problem by removing parts of the FCB underneath the MFBB regions of interest and by reducing the overall FCB layer thickness our technology provides a powerful yet versatile toolset for microfluidic cell culture applications The mLSI MFBB was designed in CleWin Layout Editor (version 4.3.6.0) The 64 chambers each measured 1.85 mm × 0.35 mm in length by width and had rounded corners The design for the flow layer was scaled by a factor of 1.01 to compensate for PDMS shrinkage the valve and bridge designs included tolerances of a few tens of micrometers to facilitate later alignment of the flow and control layers For each mLSI MFBB type (see Fig. S2) one for the control layer and one for the flow layer were prepared by standard photolithography USA) was used to create 20-µm-high channels USA) was first used to create rectangular channels approximately 48 µm high in the places where there are no valves in the design Germany) was used to create channels with a rounded profile Channel heights were measured with a Dektak® stylus profiler (Veeco all structures were created using AZ40XT photoresist Both types of mLSI MFBBs were fabricated by multilayer soft lithography17 The Netherlands) offset ratio was used to bond the flow (1:7 w/w curing agent to base polymer) and control (1:20 w/w curing agent to base polymer) layers together degassed and poured over the respective wafer the PDMS was spin-coated to achieve a layer thickness of approximately 30 µm Both wafers were cured at 60 °C for 45 min and the in- and outlets were punched using a 1-mm hole puncher (Ted Pella The flow layer was aligned on top of the control layer using an Olympus stereomicroscope The layers were cured together at 60 °C overnight the chip was plasma-bonded using a plasma cleaner (model CUTE South Korea) to a glass slide 3 cm × 6 cm × 1 mm in size with 1-mm-diameter powder-blasted holes in the locations of the control channel inlets For the unmounted chip used in the cell experiments the inlets for the control channels were punched using a 0.75-mm hole puncher (Harris Uni-core) before plasma-bonding the chip to a 1-mm-thick glass microscope slide 80% of all the mLSI MFBBs that were fabricated had at least 60 out of 64 (93–100%) fully independently operable chambers The reason why in some cases not all 64 chambers were independently operable is that the valve membrane was not even in thickness over the entire chip This resulted in areas where the pressure in the control channels was insufficient to close the valve fully flow and control channel crossings that were supposed to remain open started to close off chips that were cut from the center of the control layer wafer did not suffer from this issue indicating that the main underlying cause is the photoresist being slightly thicker at the edges Each side of the layers intended to form a bonded interface was exposed to chloroform (Sigma-Aldrich) vapor for 4 min followed by being aligned and pressed together in a custom holder using a heated hydraulic press the temperature was reduced to room temperature over 10 min by water cooling The bonded chips were then left overnight before being used Inlet and outlet tubing was connected using an NOA 81 optical adhesive FCB fabrication was outsourced to Micronit Microtechnologies (The Netherlands) The five layers were made from thermoplastic polystyrene and the flexible membrane from elastomeric SEBS All channels in the layers were micromilled Holes in the membrane for interlayer channel connections were created using a drag knife on a CNC machine The layers were bonded together by thermal compression bonding the first one used for experimental testing was fully functional and therefore was used for all experiments presented in this article The same FCB and auxiliary parts remained fully functional throughout the series of experiments for platform testing All of the valves in the MFBBs and the FCB were driven by pneumatic actuation which were hooked up to a pressurized airline via a pressure regulator (Festo were used to switch between pressurized air (approximately 1.5 bar relative pressure) and atmospheric pressure (0 bar relative pressure) The solenoid valves were controlled through a custom LabView (2017 The flow through the MFBBs was controlled using a pressure pump (Fluigent Germany) and set using the aforementioned LabView program The custom LabView program contained functions for automated coating and filling of the channels and chambers in the mLSI MFBB scripts to control different MFBBs on a single FCB (e.g. the mLSI and dosing MFBBs) could be loaded and run the platform still requires an experienced user for robust leak-free assembly due to the variable O-ring compression described in the fabrication results section and it can even be left unattended while a function or script is running For experiments not presented in this article four persons with no previous experience in microfluidics were able to successfully operate unmounted mLSI MFBBs similar to the one presented here after having had one introductory training session and a few independent tries on their own Nine 1-mm-diameter stainless steel pins (ERIKS BV The Netherlands) were inserted into the nine corresponding holes in the FCB for MFBB alignment The Netherlands) with an outer diameter of 2.3 mm were inserted into the EIB on one end and hooked up to the solenoid valves on the other end the MFBBs were aligned on the FCB and then clamped into place FKM O-rings with an inner diameter of 0.74 mm (ERIKS BV The clamp was fastened using M2 hex bolts (DIN 934) inserted from the bottom of the FCB and tightened at the top with M2 nuts (RVS Paleis BV The pressure in the tubing for the MFBB control channels was increased to 1.6 bar by switching the solenoid valves that pushed the water through the FCB Water-filled control channels prevented air bubbles from forming at the valves in the mLSI MFBB flow layer during operation The flow rates for FCB valve characterization and the mLSI MFBB pressure retention experiment were measured using an L and an S flow sensor (Fluigent Switzerland) or GFP-expressing HUVECs (Angio-Proteomie USA) were cultured in collagen I-coated T75 flasks (CELLCOAT® Greiner Bio-One) until reaching approximately 80% confluency and resuspended in endothelial growth medium (EGM) (Cell Applications USA) containing 25 mM hydroxyethyl piperazine-ethanesulfonic acid (HEPES) The cell suspension was filtered through a 40-µm pore-size filter (BD Falcon™) and then seeded in the previously prepared mLSI MFBB the mLSI MFBB was prepared by selectively coating the flow channel walls to reduce cell adhesion and protein absorption and by coating the chamber walls to promote cell adhesion The MFBB was exposed to oxygen plasma using a plasma cleaner (model CUTE South Korea) to functionalize the surface with silanol groups all control channels and all flow channels were filled with sterile 100 µg/mL PLL-g-PEG (poly(l-lysine) poly(ethylene glycol)) (SuSoS Switzerland) in PBS (Sigma-Aldrich) was flushed through all the channels and kept at room temperature for half an hour 0.1 mg/mL rat tail collagen I (Corning Life Sciences) in PBS was used to purge the PLL-g-PEG solution and then fill the chambers The collagen solution has flowed through the chambers for 3 min and the chip was then incubated for 1 h at 37 °C in the on-stage microscope incubator all of the chambers and flow channels were filled with EGM (Cell Applications Top view of the environmental box mounted on an inverted microscope Switzerland) were fixed with 4% paraformaldehyde (Sigma-Aldrich) in PBS and subsequently permeabilized with 0.3% Triton-X (Sigma-Aldrich) in PBS 15 µL/mL of both ActinRed (Thermo Fisher Scientific) and NucBlue (Thermo Fisher Scientific) was added to the Triton-X solution to visualize the F-actin filaments and nuclei Images were captured using a Leica DMI 6000 m microscope (Leica Microsystems Germany) with a pE300ultra LED illumination system (CoolLED Live-cell images of the GFP-expressing HUVECs (Angio-Proteomie USA) were taken with an EVOS FL cell imaging system using the GFP filter cube The brightness and contrast of all images were adjusted using ImageJ Microfluidic cell culture systems for drug research Cell-based high content screening using an integrated microfluidic device Qualitative and quantitative analysis of tumor cell metabolism via stable isotope labeling assisted microfluidic chip electrospray ionization mass spectrometry Mesenchymal-mode migration assay and antimetastatic drug screening with high-throughput microfluidic channel networks A high-throughput microfluidic platform for mammalian cell transfection and culturing Proximity ligation assay for high-content profiling of cell signaling pathways on a microfluidic chip Functional differentiation of human pluripotent stem cells on a chip In situ characterization of the mTORC1 during adipogenesis of human adult stem cells on chip Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics Droplet microfluidic technology for single-cell high-throughput screening Microfluidic high-throughput culturing of single cells for selection based on extracellular metabolite production or consumption Microfluidic screening reveals heparan sulfate enhances human mesenchymal stem cell growth by modulating fibroblast growth factor-2 transport Microfluidic technology enhances the potential of human pluripotent stem cells Monolithic microfabricated valves and pumps by multilayer soft lithography Ultra-multiplexed analysis of single-cell dynamics reveals logic rules in differentiation Standardized and modular microfluidic platform for fast Lab on Chip system development From chip-in-a-lab to lab-on-a-chip: a portable Coulter counter using a modular platform Self-aligning Tetris-Like (TILE) modular microfluidic platform for mimicking multi-organ interactions μorgano: a Lego®-like plug & play system for modular multi-organ-chips A truly Lego®-like modular microfluidics platform A modular microfluidic architecture for integrated biochemical analysis Heeren, H. Van, et al. Design guideline for microfluidic device and component interfaces. Mfm https://doi.org/10.13140/RG.2.1.3318.9364 (2015) A versatile microreactor platform featuring a chemical-resistant microvalve array for addressable multiplex syntheses and assays Systematic investigation of protein phase behavior with a microfluidic formulator An EWOD-based micro diluter with high flexibility on dilution ratio Reconfigurable microfluidic dilution for high-throughput quantitative assays A microfluidic diluter based on pulse width flow modulation Microfluidic module for real-time generation of complex multimolecule temporal concentration profiles Developing Microfluidic Tooling for 3D Cell-Culture Development and multiplexed control of latching pneumatic valves using microfluidic logical structures PDMS absorption of small molecules and consequences in microfluidic applications Organs-on-chips: breaking the in vitro impasse Reduction of surface roughness for optical quality microfluidic devices in PMMA and COC Download references This work was supported by the VESCEL ERC Advanced Grant to A 669768) and the MFManufacturing ESCEL Joint Undertaking (grant No Nieuwkasteele and Hans de Boer for their help in setting up the environmental box on the microscope The authors also thank Johan Bomer for his help with taking the SEM images Institute for Technology-Inspired Regenerative Medicine was involved in all of the experiments and wrote the article and tested the dosing MFBB and wrote part of the article provided input on the FCB design and assisted with the FCB testing experiments assisted in designing the FCB/MFBB interface helped design the setup and mLSI MFBB fabrication fabricated the FCB and provided input on the FCB valves was involved in many standardization (ISO) discussions and provided modularity concepts provided ideas for the system design and revised the article are employed by the Micronit Microtechnologies and this work may lead to the development of products (MFBBs and FCBs) Note that modularity and platform compatibility are ensured and covered by the ISO standard (Workshop Agreement 23:2013) The remaining authors declare that they have no conflicts of interest Download citation DOI: https://doi.org/10.1038/s41378-020-00216-z Researchers in the Netherlands have developed a fluidic circuit board (FCB) platform which can be used to operate several microfluidic building blocks (MFBB) Highly integrated microfluidic chips are challenging to design and are customized for specific applications A team led by Mathieu Odijk of the University of Twente sought to make flexible design alterations of microfluidic circuits possible they developed a modular FCB platform incorporating an MFBB enabler The enabler can operate the MFBBs in parallel or selectively and can also “save” the state of an MFBB the team used their platform to combine a dosing unit and a module with 64 parallelized culture chambers These new tools offer researchers the flexibility to combine different microfluidic chips and easily create parallelized versatile culturing systems Researchers at the University of Twente have designed a tiny needle in which micro-channels can be used for extracting small liquid samples from a local area of the brain The needle is about as thick as a human hair neuroscientists are now able to monitor dynamic processes more quickly (within a few seconds) and accurately (micrometre precision) The research is to be published in the renowned scientific journal as a result of which neuroscientists have struggled to answer such questions as ‘Why does one person get a migraine attack Doctor Mathieu Odijk of the BIOS lab-on-a-chip group explains it is important to be able to study in detail how the brain works A key role in the working of the brain is played by the chemicals - the neurotransmitters - that carry information most existing methods for monitoring neurotransmitters in the brain are not able to do so sufficiently quickly or with such localized precision.” The small needle that has been designed by Dr Odijk and his colleagues has micro-channels through which tiny samples of liquid from a localized part of the brain can be extracted These samples are stored in minute water droplets of around 10 picolitre (one millionth of a raindrop) in oil It means the information about neurotransmitters is stored in a kind of chemical memory after which it can be processed and from which readings can be taken at a later time This invention allows neuroscientists to monitor dynamic processes in the brain within a few seconds and to micrometre precision Metrics details Electrochemistry on graphene is of particular interest due to graphene’s high surface area high electrical conductivity and low interfacial capacitance Because the graphene Fermi level can be probed by its strong Raman signal information on the graphene doping can be obtained which in turn can provide information on adsorbed atoms or molecules the adsorption analysis was successfully performed using three electroactive substances with different electrode interaction mechanisms: hexaammineruthenium(III) chloride (RuHex) ferrocenemethanol (FcMeOH) and potassium ferricyanide/potassium ferrocyanide (Fe(CN)6) The adsorption state was probed by analysing the G-peak position in the measured in-situ Raman spectrum during electrochemical experiments We conclude that electrochemical Raman spectroscopy on graphene is a valuable tool to obtain in-situ information on adsorbed species on graphene isolated from the rest of the electrochemical behaviour Our working hypothesis in this investigation is that adsorption of redox-active species on graphene can be measured by Raman spectroscopy From this hypothesis follows our research question: can we find evidence for the adsorption state during redox reactions at graphene in the Raman spectrum we measured the Raman spectra of graphene during electrochemical measurements of three electroactive substances the adsorption during electrochemical reactions differs The results are obtained using chemical vapour deposited (CVD) graphene The measured Raman spectrum Sm will then be a superposition of two spectra: the graphene with adsorbed molecules Sad and the bare graphene Sgr For the ratio between both we define an occupation factor β as follows when this factor is low β ≈ 0 solely the bare graphene spectrum is measured indicating no interaction between the graphene and the molecules in solution For a large factor β ≈ 1 the graphene is entirely occupied by adsorbed molecules which interact with the graphene and therefore change the Raman spectrum In the Raman spectroelectrochemistry experiments both peak positions are changing when electrode voltages are applied the G-peak position is displayed next to the recorded cyclic voltammograms The black line represents the graphene basal plane (the smooth homogeneous graphene crystals) and the *-symbol a grain boundary edge or other site which has a higher reactive capability The electron exchange rate is much lower at the basal plane than at the reactive sites however the vast majority of the graphene surface consists out of graphene basal In each of the two pathways a series of steps are drawn adsorption of a molecule at a reactive graphene site (b) electron exchange and adsorption for a certain average time (c) and desorption from the graphene surface (d) adsorption of a molecule to the graphene basal plane (less reactive) (f) electron exchange for some of the adsorption species and adsorption for a certain average time (g) and desorption from the graphene surface (h) the adsorption of the three redox active species during electrochemical experiments using in-situ Raman spectroscopy was studied by measuring on two graphene electrode devices After measuring the baseline in background electrolyte RuHex and FcMeOH were measured with the first graphene device Fe(CN)6 was measured using the second graphene device The voltammogram (a) shows two performed RuHex measurements and the control curve of the background electrolyte (black) The G-peak position extracted from the in-situ recorded Raman spectrum vs the applied potential (b) shows curves very similar to the control (black) The voltammogram (a) shows three performed FcMeOH measurements and the control curve of the background electrolyte (black) The G-peak position extracted from the in-situ recorded Raman spectrum vs the applied potential (b) shows curves different from the control (black) Raman spectroelectrochemistry of Fe(CN)6 at graphene electrode device 2 (measurement series 1 a,b) and subsequent Raman spectroelectrochemistry of background electrolyte (with absorbed Fe(CN)6) graphene electrode device 2 (measurement series 2 The voltammograms (a,c) show the results of a sequence of respectively five and three Fe(CN)6 measurements and the control baseline curve measured in the background electrolyte (black) The G-peak position extracted from the in-situ recorded Raman spectrum vs the applied potential (b,d) show curves different from the control (black) that respectively indicate adsorption and gradual recovery to the control curve (black) In Fig. 6b the G-peak position curve is shown During the first cycle a large horizontal shift is observed but unexpectedly red-shifted (higher G-peak position) that a shift to a more positive voltage is accompanied by a red shift For the following measurements (2–5) the pattern is slightly different the G-peak position valley is lower than in the first measurement and is slightly moving to the right with each measurement Both observations can be explained by Fe(CN)6 adsorption whereby the difference between the first and the subsequent measurements suggest that two adsorption states exist The observations are as expected for the inner-sphere redox couple Fe(CN)6 In the subsequent measurements of the G-peak position curve a clear recovery towards the control state can be seen The voltammogram however does not entirely recover to the situation of the control experiment The residual current could be caused by a fraction of defect-adsorbed Fe(CN)6 that is hard to desorb it could be caused by a further decreased graphene charge carrier concentration In Section S2.3 the results of the graphene device 1 tested with Fe(CN)6 can be found showing to what extent the device history influences its behaviour and the amount of reacting species were directly coupled as for such substances redox activity is independent of adsorption whereby it could not be established whether this adsorption contributes to the redox activity The results for Fe(CN)6 were also in line with expectations as we observed both adsorption and electroactivity for this inner sphere redox couple We however observed in the Fe(CN)6 desorption experiments that two type of reactions occur The latter one has a major contribution to the current The former one is persistent and remains when the solution is flushed For larger currents (I > ~ 1 μA) a lower conductivity affects the voltammogram by increasing the required overpotential (shifting the peaks to more extreme voltages) and lowering the current peak heights Evidence for the adsorption state during redox reactions at graphene in the Raman spectrum was found Prior to every experiment a G-peak position curve was recorded for the bare graphene serving as a baseline for subsequent measurements For RuHex no change in the G-peak position curve was found during the electrochemical experiment compared to the baseline in solely background electrolyte In case of FcMeOH a clear stable negative shift in the G-peak position curve was observed indicating a strong adsorption state to the graphene potentially caused by π-interactions or electrostatic interactions For Fe(CN)6 a clear positive shift in the G-peak position curve could be seen however for this species the measurement required some time to settle towards a constant voltammogram and G-peak position curve This is suggesting that FcMeOH and Fe(CN)6 interact differently with the graphene when measuring Fe(CN)6 on the graphene electrode after FcMeOH we found no clear difference in the voltammogram compared to Fe(CN)6 while the G-peak position curve indicated that both species were adsorbed Based on these findings we conclude that Raman spectroelectrochemistry on graphene is a powerful tool to obtain in-situ information on adsorbed species on graphene independent of the cyclic voltammograms measured This makes graphene an even more interesting electrode material for electrochemical sensing as it allows a fundamental investigation of detailed adsorption mechanisms by Raman spectrometry We found indications that the adsorption of species for the larger part takes place on the less reactive basal plane while local reactive sites mainly determine the electrochemical behaviour We also observed additional effects of the adsorbed species to the graphene surface where a slight change in the electrochemical behaviour is most probably caused by changes in graphene charge carrier density and passivation of the surface The diffusion coefficient of the electrolyte is set to 7 × 10−10 m2/s Current is calculated by integrating the normal flux at the electrode boundary over its area and multiplying by F On t = 0 is the concentration of the reduced species 1 mM and the oxidized species are absent The transient behaviour is simulated by scanning the overpotential between −1 V and 1 V with 25 mV/s The schematic of the fabrication and measurement setup of the graphene devices are shown in Fig. S2 Chemical vapour deposited (CVD) graphene synthesized on copper foil (Alfa Aesar no 13382) is transferred to a silicon dioxide substrate using a traditional wet transfer procedure using poly(methyl methacrylate) (PMMA) as a supporting polymer Two gold electrical contacts are deposited on this graphene layer using a steel shadow mask and subsequently wire bonded to a printed circuit board (PCB) The resistance between the contact pads was measured to be 1.6 which is indicating a good contact to the graphene the gold pads and the wire bonds were covered by epoxy (hysol) leaving a graphene area for contacting the solution open of approximately 30 mm2 for both devices The setup used in this experiment as shown schematically in Fig. S2f and in Fig. S3 It allows for simultaneous recording of the Raman spectrum while performing electrochemical experiments Electrical potentials and currents are applied and measured using a Biologic SP300 potentiostat always at a scan rate of 25 mV/s with a low-pass filter (fcutoff = 5 Hz) FcMeOH and Fe(CN)6) were added in a concentration of 1 mM 100 μL of solution was applied to the graphene device All potentials were measured against an Ag/AgCl reference electrode (WPI Dri-Ref-450) The spectra are recorded using a WITec alpha 300 system with a 532 nm laser at 1 mW with an immersion objective for measuring in liquid (Nikon Fluor 40x 0.8 W DIC) Analysis of the recorded Raman spectra is performed using a MATLAB script which accounts for an offset in the spectrometer by fitting the Rayleigh peak Next Lorentzian curves are fitted to the graphene peaks to obtain their positions and intensities The voltammetric measurement protocol was as follows In each measurement three scans were performed in series (whereby the results of the last two scans are displayed) Measurements in a series were performed with a time spacing of approximately 1 minute In-situ Raman spectroscopy to elucidate the influence of adsorption in graphene electrochemistry Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Room-temperature quantum hall effect in graphene Impermeable atomic membranes from graphene sheets Recent progress in the growth and applications of graphene as a smart material: A review Graphene based electrochemical sensors and biosensors: a review Interfacial capacitance of graphene: Correlated differential capacitance and in situ electrochemical raman spectroscopy study Graphene-based materials in electrochemistry Electrochemistry of individual monolayer graphene sheets The edge-and basal-plane-specific electrochemistry of a single-layer graphene sheet Electrochemical properties of cvd grown pristine graphene: monolayer-vs Graphene electrochemistry: an overview of potential applications Label-free detection of dna hybridization using transistors based on cvd grown graphene Electrical detection of dna hybridization with single-base specificity using transistors based on cvd-grown graphene sheets Raman fingerprint of doping due to metal adsorbates on graphene Changes in the electronic structure and properties of graphene induced by molecular charge-transfer Electric field effect tuning of electron-phonon coupling in graphene Monitoring dopants by raman scattering in an electrochemically top-gated graphene transistor Raman spectroscopy and in situ raman spectroelectrochemistry of bilayer 12c/13c graphene Raman spectroscopy as a tool to address individual graphene layers in few-layer graphene The influence of strong electron and hole doping on the raman intensity of chemical vapor-deposition graphene In situ raman spectroelectrochemistry of graphene oxide Raman spectroscopy and in situ raman spectroelectrochemistry of isotopically engineered graphene systems Ultrafast dynamics of plasmon-exciton interaction of ag nanowire-graphene hybrids for surface catalytic reactions Au-ag-cu nano-alloys: tailoring of permittivity Recent progress in the applications of graphene in surface-enhanced raman scattering and plasmon-induced catalytic reactions Response time of nanofluidic electrochemical sensors Electrochemical methods: fundamentals and applications Understanding the difference between inner-and outer-sphere mechanisms: An electrochemical experiment Electrochemical correlation spectroscopy in nanofluidic cavities defects and electronic structure: general discussion Detection of individual gas molecules adsorbed on graphene Quantitative correlation between defect density and heterogeneous electron transfer rate of single layer graphene Journal of the American Chemical Society 136 Electrochemistry at carbon nanotubes: perspective and issues Instrumental methods in electrochemistry (Elsevier Electronic properties of grains and grain boundaries in graphene grown by chemical vapor deposition Origin of the relatively low transport mobility of graphene grown through chemical vapor deposition Healing defective cvd-graphene through vapor phase treatment Simulation of redox-cycling phenomena at interdigitated array (IDA) electrodes: Amplification and selectivity Download references Financial support from Spinoza Grant of Albert van den Berg is acknowledged MESA+ Institute for Nanotechnology and MIRA Institute for Biomedical Engineering and Technical Medicine The manuscript was written through contributions of all authors All authors have given approval to the final version of the manuscript Graphene synthesis experiments were performed by R.H.J.V conceived and analysed the electrochemical Raman spectroscopy on graphene experiments and simulations assisted with experiments analysis and manuscript writing The authors declare no competing financial interests Download citation Sign up for the Nature Briefing newsletter — what matters in science who is in the penultimate semester of the dietician program in Gothenburg was one of 38 students who completed the mapping She visited patients in the surgery department of Kungälv Hospital For her it was a very positive and educational experience: “There can be many different reasons to malnutrition It became clear to me during the day at the hospital that you really have to work in a person-centered way because not everyone has the same requirements others need more general tips and tricks,” says Wilma A person who suffers from malnutrition loses weight is deficient in nutrients and has problems with muscle breakdown They may also become more susceptible to infection and will require more care which can lead to longer hospital stays and higher mortality rates According to a recent review article in the New England Journal of Medicine up to half of all patients admitted to hospitals and other healthcare facilities are malnourished which can have many causes and different solutions In healthcare it can also be difficult to make the right risk assessment It felt good to contribute with a baseline that gives the department the opportunity to evaluate its work with malnutrition,” says Wilma Ebenholm Pettersson the students were asked to interview patients in a healthcare department how much food the patient had eaten for lunch that day The departments had prepared and selected patients who were able to be visited by the students “In addition to giving students practice in their encounters with patients the course provides lessons for healthcare,” says Senior Lecturer Jenny van Odijk: “The responses collected by the students will now be compiled anonymously and the departments can then use the results to suggest improvements to reduce the problem in the departments concerned So the collaboration gives students an insight into clinical practice and dietitians and health departments a tool to evaluate and potentially improve malnutrition in healthcare.” This interactive element is planned to be a recurring collaboration between the dietitian program and the healthcare services.  This year Alingsås Hospital and Sahlgrenska University Hospital (Östra Hospital and Sahlgrenska) participated Find organisation Despite the large number of scientific publications in the microfluidic field in the current market there is a large gap between the lab and fab environment The project tries to close this gap by organizing the industrial partners in the project into a distributed pilot line A second point the project tries to improve is the standardization in the microfluidic field This standardization should make it possible to buy COTS (Commercial Of The Self) microfluidic components and interconnect them to form a microfluidic product This prohibits the need for companies to do the whole research manufacturing and product testing in-house Standardization will focus on elementary devices chip-to-world interconnection and an interposer (like a printed circuit board (PCB) in the electronics world) Our role: Within this large European project MESA+ will focus mainly on the development of (1) microfluidic elementary devices using standardized interconnects and (2) the development of a microfluidic circuit board (MCB) as the fluidic equivalent to a PCB Project Website: Home - Microfluidics Assciation (microfluidics-association.org)/ Electrochemical Reactions on-chip - Combinations with Mass Spectrometry for Drug Screening and Proteomics The PhD defence of Pascal Führer will take place (partly) online The PhD defence can be followed by a live stream Pascal Führer is a PhD student in the research group Biomedical and Environmental Sensorsystems (BIOS) Odijk from the Faculty of Electrical Engineering In the pursuit of developing new tools for drug development and analytical proteomics this thesis deals with research questions regarding fast drug metabolism mimicry and streamlined proteomic workflows Both of these questions are present in current life science applications where a lot of time and effort are spent that can be significantly reduced through modern integrated and electrochemical on‑chip solutions This thesis presents the potential of electrochemistry hyphenated to spectroscopic and spectrometric methods by means of a critical literature review namely chip electrochemistry hyphenated to trapped ion mobility spectrometry followed by a time‑of‑flight separation in a high‑resolution mass spectrometer (chipEC‑TIMS‑ToF‑HRMS) at the example of phase I and II mimicry of ethoxyquin and paracetamol The electrode material boron‑doped diamond (BDD) has shown good qualities for metabolism mimicry and oxidative peptide cleavage in recent years and was further investigated for biofouling occurring in a simple chip The chips were fabricated with an adhesive tape as fluidic patterning and bonding agent exploring new fabrication techniques for a more streamlined chip development a new complex chip design incorporating three subsystems for a completely integrated proteomics workflow was created This design was partially realized in a set of chips with which preliminary data for the electrochemical cleavage reactions was generated this thesis combines different approaches to furthering microfluidic approaches to modern life science problems ranging from complex method hyphenations and chip designs to new fabrication methods Analysis of Transient Electrochemical Processes by Mass Spectrometry - Ethanol Oxidation and Nitrate Reduction Ainoa Paradelo Rodríguez is a PhD student in the department Photocatalytic Synthesis Mei from the faculty of Science & Technology and prof.dr.ir Odijk from the faculty of Electrical Engineering This PhD thesis goes from the fundamentals of electrochemical reactions to the application we evaluate the Electrochemistry - Mass Spectrometry (EC-MS) setup for the fundamental mechanistic study of electrochemical reactions over metal surfaces the electro-oxidation mechanism of ethanol over a platinum surface and the electrochemical reduction of nitrate to ammonia over Ti Ag and bimetallic TiAg electrodes have been investigated there have been collaborations using the EC-MS for other reactions that confirmed the sensitivity and versatility of this instrument in several applications we focus on the application of the acquired mechanistic knowledge in the nitrate electrochemical reduction over TiAg for more practical purposes using Ti hollow fiber electrodes The ethanol electrochemical oxidation reaction on Pt in acidic media has been investigated in Chapter 2 ethylene was revealed as an intermediate product the hydrogenation of ethylic fragments was proven by performing experiments with H2 pulses Chapter 3 presents a summary of the different studies in which the use of EC-MS facilitated the investigation of electrochemical reaction mechanisms Some of the reactions investigated are the (non)-Kolbe reaction and nitrate reduction on Ti the high sensitivity of the setup allowed us to detect small amounts of NO produced by a chemical donor the possibility of using a gaseous reactant as a gas carrier allowed the detection of intermedia products in NO reduction and CO2 reduction with nitrate in the electrolyte on Cu The nitrate reduction mechanism of bimetallic TiAg electrodes was investigated in Chapter 4 chronoamperometry measurements showed a lower overpotential at enhancement in Faradaic efficiency of the TiAg electrodes in comparison to the pure metals (Ti the synergy between the metals was revealed by the pronounced enhancement of NO evolution detected by the EC-MS Ti tubular porous electrodes were modified with Ag particles to evaluate the catalytic performance of the bimetallic material and to understand the influence of mass transport in Chapter 5 A  significant dependence of the performance of the electrode on mass transport was discovered Microdevices for High-Throughput Screening of Single Catalyst Particles Alessia Broccoli is a PhD student in the department Biomedical and Environmental Sensorsystems van den Berg from the faculty of Electrical Engineering Mul from the faculty of Science & Technology and dr Meirer from the Department of Chemistry at Utrecht University Heterogeneous catalysis is a dynamic field with a continuous focus on improving and developing more efficient Solid catalysts can exhibit different sizes They are often porous particles with structural features that cover length scales from nanometers to centimeters as they include sub-nanometer active catalytic sites nanometer-scale metal clusters or nanoparticles This range of structural features highlights the complexity of solid catalysts with each component and hierarchical arrangement playing a significant role in their catalytic functions understanding and characterizing these materials is crucial for elucidating structure-activity relationships and developing catalysts with improved performance Traditionally characterization of catalyst particles is done in bulk providing individual features of catalysts such as concentration of active sites or accessibility as an ensemble average over millions or billions of catalyst particles Using that information for interpreting performance as well as enhancing the design of the catalyst requires the underlying assumption of uniformity in the properties across the individual particles in a catalyst batch may not always hold true given the variability that can exist at multiple scales (intra- and inter-particle heterogeneity) microfluidic devices have emerged as powerful tools for accelerating catalyst development and characterization at the single-particle level They allow for isolating and examining individual particles under controlled experimental conditions and hold a unique advantage in their capability for high-throughput analysis This thesis presents microdevices that enable the characterization of individual catalytic particles in terms of accessibility and activity We explored high-throughput strategies based on the use of multiplexed devices with parallel chambers containing different particles or the analysis of spatially resolved particles with a continuous flow system The high-throughput screening approach allows for rapid testing of multiple particles or conditions while also resolving particle heterogeneities Microreactors for In Situ Single Catalyst Particle Characterization Using Advanced Imaging Techniques Luca Carnevale is a PhD student in the department Biomedical and Environmental Sensorsystems Olthuis from the faculty of Electrical Engineering Mathematics and Computer Science and prof.dr.ir Heterogeneous catalysts are characterized by a multi-length scale structure with a complex pore network that exhibits specific tortuosity and pore connectivity This structure plays a crucial role in catalytic processes defining the activity and selectivity towards specific reaction products A spatial and time-resolved structure-activity relationship is fundamental to enhance and improve catalyst performance Traditional characterization methods for solid catalysts typically provide averaged information across the analyzed batch of particles overlooking the intra and interparticle heterogeneities inherent in these materials Exploring solid catalysts at varying depths and during operations (in situ or operando) allows us to obtain complementary information which is crucial for obtaining a comprehensive understanding of the underlying mechanisms governing catalytic reactions This thesis contributes to the advancement of innovative microfluidic devices for investigating heterogeneous catalysts at the single particle level in real reaction conditions The microfluidic devices presented in the thesis allow for in situ imaging of compositional and structural changes of individual catalyst particles using 3D high-resolution X-ray microscopy and studying the influence of the particle porosity (pore size surface area) on mass transport at the single particle level The Asian hornet is advancing in the northern part of the Netherlands, according to Stop Invasieve Exoten, a platform tracking the presence of invasive species in the country. The Asian hornet is harmful to honey bees, wild bees and other insects. The organization deduced the hornet is advancing in a northerly direction from reports submitted via Waarneming.nl Groningen and Friesland are now the only remaining provinces where it has not knowingly been seen and one had already been seen in Lunteren on May 4 A sighting of a queen was received from Odijk Reports have also been submitted from other provinces the hornet has been seen for a longer time There have been 15 confirmed reports of queens this year from people based in Limburg About forty finds of queens have been reported in Noord-Brabant this year The first discovery of the Asian hornet in the Netherlands was made in 2017 in Dreischor "To prevent this harmful invasive exotic species from spreading even further in the Netherlands as much as possible it is important that the nests are quickly traced and destroyed because without observations the provinces do not take action," says Wilfred Reinhold The large, dark Asian hornet workers are more common this time of year, and can be identified by an abdomen that is almost entirely black, a small, yellow-orange spot at the tip, and yellow-tipped legs. Anyone who spots one should either try to take a photo of it or catch it, and file a report on Waarneming.nl they can be fitted with a transmitter that can help researchers locate the nest the platform asked people not to kill the hornets when they are observed The hornets are not to be confused with the Asian giant hornets sometimes referred to as “murder hornets.” They are predatory and also very large with stingers long enough to penetrate protective clothing Independent journalism at the University of Twente dozens of UT professors call for participation in the March 25 relay strike in Enschede and for the future of the University of Twente.' At the University of Twente we will be on strike on March 25th This strike is directed against the education budget cuts planned by the current government We are striking in protest against a government that wants to push through unprecedented budget cuts that are unnecessary other universities across the Netherlands will also strike Following the example of our colleagues in Utrecht and Nijmegen we hereby make the same appeal: strike with us Healthy universities are crucial for a flourishing democracy which are essential for an engaged society The planned cuts threaten academic freedom A weakened university system means a weakened democracy The University of Twente distinguishes itself through its unique combination of technical and social sciences with focus and potential for inter- and transdisciplinary research aimed at the impact domains of health This education and research profile is crucial for the major societal transitions that lie ahead The planned cuts threaten this unique profile and thus our capacity to provide innovative solutions for the complex societal challenges we are therefore laying down our work and organizing alternative actions We find this difficult because we are passionate about research and education circumstances call for unprecedented action so that the government and opposition realize that the budget cuts will cut very deeply into the system They must also realize that the consequences for workload and economic impact will be very significant We are already seeing this negative impact around us as universities are forced to take an advance on the cuts but it is precisely by going on strike that you stand up for scientific research and education So join the strike - stand up for knowledge and for the future of the University of Twente Lars van de Zandschulp (25) is masterstudent technische bedrijfskunde en is routinier in het Enschedese studentenleven Hij schrijft om de week een column voor U-Today over wat hem opvalt in de stad en op de campus Vandaag: over kanalen en een vuurwapengevaarlijke cantus Jenna Zaagsma (22) is masterstudent educatie in de bètawetenschappen en biomedische technologie Drie dagen in de week staat ze voor de klas als leraar natuurkunde in haar vrije tijd is ze te vinden bij studentenscouting Radix en vechtsportvereniging Arashi Ze schrijft over haar belevenissen en wat haar bezighoudt op en rondom de campus De beleidsregel die universiteiten dwingt om afscheid te nemen van betaalbare sport en cultuur is in potentie de doodsteek voor de campusgedachte maar ook het DNA van de UT staat op het spel Vandaag: over pretvakken en vendetta’s met professoren With the magazine ROOTS we want to connect students and companies We do this by bringing stories of starters on the labor market They talk about living and working in the region companies come into the spotlight of students and students get an idea of the life that awaits them and what opportunities there are in the region.