Search

Competing Interests: Supported by grants from the Swedish Research Council; the 10.13039/501100004359Swedish Research Council for 10.13039/100018696Health, Working Life, and Welfare; Formas; the Swedish Asthma and Allergy Research Foundation; the Swedish Heart-Lung Foundation; and Region Stockholm (the ALF project, and for cohort and database maintenance). Disclosure of potential conflict of interest: E. Melén reports personal fees from 10.13039/100004325AstraZeneca, Chiesi, Sanofi, and Novartis outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.

Background: Self-sampling of dried blood spots (DBS) offers new routes to gather valuable health-related information from the general population. Yet, the utility of using deep proteome profiling from home-sampled DBS to obtain clinically relevant insights about SARS-CoV-2 infections remains largely unexplored., Methods: Our study involved 228 individuals from the general Swedish population who used a volumetric DBS sampling device and completed questionnaires at home during spring 2020 and summer 2021. Using multi-analyte COVID-19 serology, we stratified the donors by their response phenotypes, divided them into three study sets, and analyzed 276 proteins by proximity extension assays (PEA). After normalizing the data to account for variances in layman-collected samples, we investigated the association of DBS proteomes with serology and self-reported information., Results: Our three studies display highly consistent variance of protein levels and share associations of proteins with sex (e.g., MMP3) and age (e.g., GDF-15). Studying seropositive (IgG + ) and seronegative (IgG - ) donors from the first pandemic wave reveals a network of proteins reflecting immunity, inflammation, coagulation, and stress response. A comparison of the early-infection phase (IgM + IgG - ) with the post-infection phase (IgM - IgG + ) indicates several proteins from the respiratory system. In DBS from the later pandemic wave, we find that levels of a virus receptor on B-cells differ between seropositive (IgG + ) and seronegative (IgG - ) donors., Conclusions: Proteome analysis of volumetric self-sampled DBS facilitates precise analysis of clinically relevant proteins, including those secreted into the circulation or found on blood cells, augmenting previous COVID-19 reports with clinical blood collections. Our population surveys support the usefulness of DBS, underscoring the role of timing the sample collection to complement clinical and precision health monitoring initiatives., (© 2024. The Author(s).)

Background: Asthma was initially described as a risk factor for severe coronavirus disease 2019 (COVID-19), but the uptake of COVID-19 vaccine among young adults with asthma is not well studied., Objective: The aims were to assess COVID-19 vaccine uptake among young adults in general and to explore potential determinants including sociodemographic factors and asthma., Methods: Participants from the population-based birth cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) were included: 4,064 in the study population, 3,064 in a follow-up at age 24 years, and 2,049 in a COVID-19 follow-up (mean age, 26.5 years). Asthma and asthma-associated characteristics were assessed through questionnaires and clinical data. Data on all COVID-19 vaccines registered between January 1, 2021, and February 15, 2023, were extracted from the National Vaccination Register., Results: In the study population (n = 4,064), 53.9% had ≥3 COVID-19 vaccine doses registered. In the 24-year follow-up population (n = 3,064), vaccine uptake differed in relation to education ( P  < .001). Among the participants with university/college education, 65.7% had an uptake of ≥3 doses of vaccine, compared to 54.1% among the participants with elementary school/high school education. Participants with asthma had decreased odds of receiving ≥3 doses (adjusted odds ratio = 0.62; 95% confidence interval, 0.41-0.92) and ≥2 compared to peers without asthma. Those with uncontrolled disease also had decreased odds of receiving ≥3 doses (adjusted odds ratio = 0.30; 95% confidence interval, 0.13-0.66) and ≥2 compared to participants with controlled asthma., Conclusions: COVID-19 vaccine uptake among young adults is lower in individuals from households with lower socioeconomic status and among those with asthma, including uncontrolled asthma., Competing Interests: Supported by grants from the 10.13039/501100004359Swedish Research Council, the 10.13039/501100006636Swedish Research Council for Health, Working Life and Welfare, 10.13039/501100001862Formas, Swedish Asthma and Allergy Research Foundation, the Swedish Heart–Lung Foundation, and Region Stockholm (ALF project, and for cohort and database maintenance). Disclosure of potential conflict of interest: E. Melén reports personal fees from AstraZeneca, Chiesi, Sanofi, and Novartis outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest., (© 2024 The Authors.)

Cytobrushes are used for low-invasive sample collection and screening in multiple diseases, with a significant impact on early detection, prevention, and diagnosis. This study focuses on improving the safety of cell brushing in hard-to-reach locations by exploring brush construction from absorbable materials. We investigated the efficacy of loop brushes made of absorbable suture wires of Chirlac, Chirasorb, Monocryl, PDS II, Vicryl Rapid, Glycolon, and Catgut during their operation in conjunction with fine-needle aspiration in an artificial cyst model. PDS II brushes demonstrated the highest efficiency, while Monocryl and Catgut also provided a significant brushing effect. Efficient brushes portrayed higher flexural rigidity than their counterparts, and their efficiency was inversely proportional to their plastic deformation by the needle. Our results open avenues for safer cell biopsies in hard-to-reach locations by utilizing brushes composed of absorbable materials., (© 2023. The Author(s).)

Blood sampling is a common practice to monitor health, but it entails a series of drawbacks for patients including pain and discomfort. Thus, there is a demand for more convenient ways to obtain samples. Modern analytical techniques enable monitoring of multiple bioanalytes in smaller samples, opening possibilities for new matrices, and microsampling technologies to be adopted. Interstitial fluid (ISF) is an attractive alternative matrix that shows good correlation with plasma concentration dynamics for several analytes and can be sampled in a minimally invasive and painless manner from the skin at the point-of-care. However, there is currently a lack of sampling devices compatible with clinical translation. Here, to tackle state-of-the-art limitations, a cost-effective and compact single-microneedle-based device designed to painlessly collect precisely 1.1 µL of dermal ISF within minutes is presented. The fluid is volume-metered, dried, and stably stored into analytical-grade paper within the microfluidic device. The obtained sample can be mailed to a laboratory, quantitatively analyzed, and provide molecular insights comparable to blood testing. In a human study, the possibility to monitor various classes of molecular analytes is demonstrated in ISF microsamples, including caffeine, hundreds of proteins, and SARS-CoV-2 antibodies, some being detected in ISF for the first time., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Background: Lithium is a cornerstone in the treatment of bipolar disorder and is considered one of the most effective treatments in psychiatry at large. Lithium treatment requires individual dosing with frequent serum concentration measurements due to the narrow therapeutic window and risk of toxicity. There is need for patient-centric methods for lithium monitoring and the use of dried blood spots has recently been proposed for determination of lithium concentration. The purpose of the current study was to assess feasibility of this method by introducing a volumetric technique developed for home-sampling., Materials and Methods: Laboratory: Capillary blood was sampled by finger-prick using a volumetric device that collects 10 µL volumes as a dried blood spot. Lithium was measured in the dried blood spots using a validated atomic absorption spectroscopy method., Clinical: Thirty-nine lithium-treated patients were recruited, and dried blood spots and venous blood samples were collected. Routine serum analysis was performed for comparison., Results: The range of serum lithium concentrations was 0.41-1.22 mmol/L, and the dried blood spot/serum ratio was 0.78. A strong linear correlation between the two specimens was shown with Pearson's R = 0.95 (r 2 = 0.90). Adding hematocrit as a variable only minimally improved prediction., Conclusion: Volumetric dried blood spots is a promising technique for measurement of lithium concentrations. This will enable home-sampling and could potentially save resources, improve compliance, and make treatment safer. This may facilitate the use of lithium treatment in regions where monitoring via venous blood sampling remains difficult. However, the usability of dried blood spots for monitoring lithium treatment longitudinally remains to be examined., Competing Interests: Declaration of Competing Interest NR and OB are co-founders of Capitainer AB, a company commercializing Capitainer qDBS microsampling cards. All other authors declare no conflicts of interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Patient-centric sampling strategies, where the patient performs self-sampling and ships the sample to a centralized laboratory for readout, are on the verge of widespread adaptation. However, the key to a successful patient-centric workflow is user-friendliness, with few noncritical user interactions, and simple, ideally biohazard-free shipment. Here, we present a capillary-driven microfluidic device designed to perform the critical biomarker capturing step of a multiplexed immunoassay at the time of sample collection. On-chip sample drying enables biohazard-free shipment and allows us to make use of advanced analytics of specialized laboratories that offer the needed analytical sensitivity, reliability, and affordability. Using C-Reactive Protein, MCP1, S100B, IGFBP1, and IL6 as model blood biomarkers, we demonstrate the multiplexing capability and applicability of the device to a patient-centric workflow. The presented quantification of a biomarker panel opens up new possibilities for e-doctor and e-health applications.

Rapid on-site evaluation (ROSE) increases the diagnostic accuracy of fine-needle aspiration (FNA) samples from cysts, a sack-like fluid-containing tissue that sometimes can be precancerous, but is highly dependent on the skills and availability of cytopathologists. We present a semiautomated sample preparation device for ROSE. The device consists of a smearing tool and a capillary-driven chamber that allow smearing and staining of an FNA sample in a single platform. Here, we show the capability of the device to prepare samples for ROSE, using a human pancreatic cancer cell line (PANC-1) and liver, lymph node, and thyroid FNA model samples. Using microfluidics, the device reduces the equipment needed in an operating room for FNA sample preparation, which may lead to a wider implementation of ROSE in healthcare centers., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Pulmonary drug delivery by portable inhalers is the gold standard in lung disease therapy. An increasing focus on environmentally friendly inhalation currently spurs the development of propellant-free devices. However, the absence of propellants in the drug creates a need for suitable sealing systems that can ensure the pathogenic safety of devices. Traditionally, liquid drug inhalers incorporate a spray nozzle and a separate check valve. Here we show a fully integrated MEMS-based spray system for aqueous drug solutions and demonstrate its bacterial safety. The device comprises a thin silicon membrane with spray orifices, which self-seal against a compliant parylene valve seat underneath. This sealing system prevents bacterial ingrowth in its default closed state, while actuation lifts the membrane from the valve seat upon pressurization and sprays an inhalable aerosol from the nozzles. To seal against bacterial contamination effectively, we found that a contact force between the valve seat and the membrane (featuring the spray nozzles) is needed. In our testing, both self-sealing and an otherwise identical unvalved version of the spray chip can be bacterially safe in continued use when thoroughly cleaned of excess fluids and subjected to low bacterial loads for brief periods. However, when directly exposed to [Formula: see text] CFU/ml of our test organism Citrobacter rodentium for 24 h, unvalved systems become contaminated in nearly 90% of cases. In contrast, self-sealing spray chips reduced contamination probability by 70%. This development may enable preservative-free drug formulations in portable inhalers that use propellant-free aqueous drug solutions., (© 2022. The Author(s).)