| 1. |
- Beck, Olof, et al.
(författare)
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Volumetric dried blood spots for determination of phosphatidylethanol: Validation of a liquid chromatography tandem masspectrometry method and clinical application
- 2024
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Ingår i: DRUG TESTING AND ANALYSIS. - 1942-7603 .- 1942-7611.
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Tidskriftsartikel (refereegranskat)abstract
- Phosphatidylethanol (PEth) measurement in whole blood samples is established as a specific alcohol biomarker with clinical and forensic applications. Establishment of dried blood spots (DBSs) as a specimen for PEth determination offers several advantages and was the focus of this work. A liquid chromatography tandem mass spectrometry method using a 96-well format for sample preparation was developed and validated. PEth was extracted from DBSs by using isopropanol containing PEth-d5 as internal standard. The blood sampling used a commercial volumetric DBS device having a phosholipase D inhibitor incorporated to stop continuous PEth formation. The method quantified PEth in the range of 0.05-10 mu mol/L, with a bias and imprecision of less than 15%. In a clinical study (n = 25) using fingerprick blood, the volumetric device offered more precise quantifications (CV 4.6%) compared with the Whatman 903 Protein Saver card device (CV 16.6%). In another clinical study (n = 48), the use of dried venous and capillary blood, and liquid venous blood was compared under real-life conditions with samples sent by postal service. The capillary and venous DBS samples gave identical results while the liquid blood gave slightly higher values. Calculation of elimination half-life (PEth 16:0/18:1) in 31 cases based on two consecutive samples with 2-9 days in between gave results (mean 6.2 days) that agree with literature but several cases with values over 10 days. In conclusion, this study demonstrates that volumetric DBS is a valid specimen for determination of PEth blood concentrations, offering several advantages. Phosphatidylethanol, a specific alcohol biomarker, measured in dried blood spots was the focus of this work. A liquid chromatography tandem mass spectrometry method was developed, validated, and applied. The blood sampling used a volumetric DBS device. The volumetric device gave accurate and precise quantifications and the dried capillary blood gave the same results as that of venous blood. image
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| 2. |
- Fredolini, Claudia, et al.
(författare)
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Proteome profiling of home-sampled dried blood spots reveals proteins of SARS-CoV-2 infections
- 2024
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Ingår i: Communications Medicine. - : Springer Nature. - 2730-664X. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- 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. The COVID-19 pandemic has posed multiple challenges to healthcare systems. A significant gap that remains is a lack of understanding of the impact of SARS-CoV-2 on individuals who did not seek or require hospitalization. To address this, we distribute self-sampling devices to random citizens, aiming to analyze how blood protein levels are affected in people who have had COVID-19 but had no or mild symptoms. Conducting multiple molecular measurements in dried blood, our study confirms clinically known markers and their relationship to infection stages, even if the donors themselves collect the sample. Our work highlights the potential of combining self-sampling with laboratory methods to provide useful information on human health. This convenient patient-centric sampling approach may potentially be useful when studying other diseases. Fredolini et al. present a proteomics analysis of home-sampled dried blood spots taken from the general population in Stockholm during the COVID-19 pandemic. The study provides insights into the molecular effects of SARS-CoV-2 infection in non-hospitalized individuals and demonstrates the compatibility of self-sampled blood spots with proteomics.
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| 3. |
- Hauser, Janosch, et al.
(författare)
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Microfluidic Device for Patient-Centric Multiplexed Assays with Readout in Centralized Laboratories
- 2023
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 95:2, s. 1350-1358
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Ribet, Federico, et al.
(författare)
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Microneedle Patch for Painless Intradermal Collection of Interstitial Fluid Enabling Multianalyte Measurement of Small Molecules, SARS‐CoV‐2 Antibodies, and Protein Profiling
- 2023
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Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 12:13
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Wikström, Fredrik, et al.
(författare)
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Determination of lithium concentration in capillary blood using volumetric dried blood spots
- 2023
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 227, s. 115269-
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Tidskriftsartikel (refereegranskat)abstract
- 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 mu L 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 (r2 = 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.
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| 6. |
- Dobielewski, Mikolaj, et al.
(författare)
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Blood Cell Quantification on Dry Blood Samples - Towards Patient-CentricComplete Blood Counts (CBC)
- 2022
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Ingår i: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Performing complete blood counts (CBC) from patients´ homes could have atransformative impact on e-based healthcare. Blood microsampling and sample drying are enablingelements for patient-centric healthcare. The aim of this study is to investigate the potential of dry bloodsamples for image-based cell quantification of red and white blood cells. Methods: A manual samplepreparation method is developed and tested for image-based red and white blood cell counting. Resultsand Conclusion: Dry blood samples enable image-based cell counting of red and white blood cells with agood correlation to gold standard hematology analyzer data (avg. CV < 6.5%, R2 > 0.8), and resolve thebasic morphology of white blood cell nuclei. The presented proof-of-principle study is a first step towardpatient-centric CBCs.
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| 7. |
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| 8. |
- Viklund, Emilia, et al.
(författare)
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Severe acute respiratory syndrome coronavirus 2 can be detected in exhaled aerosol sampled during a few minutes of breathing or coughing
- 2022
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Ingår i: Influenza and other Respiratory Viruses. - : Wiley. - 1750-2640 .- 1750-2659. ; 16:3, s. 402-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The knowledge on the concentration of viral particles in exhaled breath is limited. The aim of this study was to explore if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in aerosol from subjects with the coronavirus disease 2019 (COVID-19) during various types of breathing and coughing and how infection with SARS-CoV-2 may influence the number and size of exhaled aerosol particles. Methods: We counted and collected endogenous particles in exhaled breath in subjects with COVID-19 disease by two different impaction-based methods, during 20 normal breaths, 10 airway opening breaths, and three coughs, respectively. Breath samples were analyzed with reverse transcription real-time polymerase chain reaction (RT-PCR). Results: Detection of RNA in aerosol was possible in 10 out of 25 subjects. Presence of virus RNA in aerosol was mainly found in cough samples (n = 8), but also in airway opening breaths (n = 3) and in normal breaths (n = 4), with no overlap between the methods. No association between viral load in aerosol and number exhaled particles <5μm was found. Subjects with COVID-19 exhaled less particles than healthy controls during normal breathing and airway opening breaths (all P < 0.05), but not during cough. Conclusion: SARS-CoV-2 RNA can be detected in exhaled aerosol, sampled during a limited number of breathing and coughing procedures. Detection in aerosol seemed independent of viral load in the upper airway swab as well as of the exhaled number of particles. The infectious potential of the amount of virus detected in aerosol needs to be further explored.
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| 9. |
- Roxhed, Niclas, et al.
(författare)
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Multianalyte serology in home-sampled blood enables an unbiased assessment of the immune response against SARS-CoV-2
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Serological testing is essential to curb the consequences of the COVID-19 pandemic. However, most assays are still limited to single analytes and samples collected within healthcare. Thus, we establish a multianalyte and multiplexed approach to reliably profile IgG and IgM levels against several versions of SARS-CoV-2 proteins (S, RBD, N) in home-sampled dried blood spots (DBS). We analyse DBS collected during spring of 2020 from 878 random and undiagnosed individuals from the population in Stockholm, Sweden, and use classification approaches to estimate an accumulated seroprevalence of 12.5% (95% CI: 10.3%-14.7%). This includes 5.4% of the samples being IgG(+)IgM(+) against several SARS-CoV-2 proteins, as well as 2.1% being IgG(-)IgM(+) and 5.0% being IgG(+)IgM(-) for the virus' S protein. Subjects classified as IgG(+) for several SARS-CoV-2 proteins report influenza-like symptoms more frequently than those being IgG(+) for only the S protein (OR=6.1; p<0.001). Among all seropositive cases, 30% are asymptomatic. Our strategy enables an accurate individual-level and multiplexed assessment of antibodies in home-sampled blood, assisting our understanding about the undiagnosed seroprevalence and diversity of the immune response against the coronavirus. Here, Roxhed et al. develop a multiplexed approach to screen IgG and IgM levels against several SARS-CoV-2 proteins in home-sampled dried blood spots and estimate seroprevalence of 12.5% in Stockholm in spring of 2020.
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| 10. |
- Beck, Olof, et al.
(författare)
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First evaluation of the possibility of testing for drugged driving using exhaled breath sampling
- 2019
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Ingår i: Traffic Injury Prevention. - : TAYLOR & FRANCIS INC. - 1538-9588 .- 1538-957X. ; 20:3, s. 238-243
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Driving under the influence of psychoactive drugs causes an increased risk for accidents. In combating this, sobriety tests at the roadside are common practice in most countries. Sampling of blood and urine for forensic investigation cannot be done at the roadside and poses practical problems associated with costs and time. An alternative specimen for roadside testing is therefore warranted and the aerosol particles in exhaled breath are one such alternative.Methods: The present study investigated how the exhaled breath sample compared with the routine legal investigations of blood and urine collected from suspects of drugged driving at 2 locations in Sweden. Exhaled breath was collected using a simple filter collection device and analyzed with state-of-the-art mass spectrometry technique.Results: The total number of cases used for this investigation was 67. In 54 of these cases (81%) the results regarding a positive or negative drug test result agreed and in 13 they disagreed. Out of these, the report from the forensic investigation of blood/urine was negative in 21 cases. In 6 of these, analytical findings were made in exhaled breath and these cases were dominated by the detection of amphetamine. In 7 cases a positive drug test from the forensic investigation was not observed in the breath sample and these cases were dominated by detection of tetrahydrocannabinol in blood. In total, 45 samples were positive with breath testing and the number of positives with established forensic methods was 46.Conclusion: The promising results from this study provide support to exhaled breath as a viable specimen for testing of drugged driving. The rapid, easy, and convenient sampling procedure offers the possibility to collect a drug test specimen at the roadside. The analytical investigation must be done in a laboratory at present because of the need for a highly sensitive instrument, which is already in use in forensic laboratories. The analytical work is not more challenging than for blood or oral fluid and should not cause an increase in cost. However, more studies need to be done before exhaled breath drug testing can be applied routinely for drugged driving investigation.
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