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Mass Spectrometry (Tokyo, Japan) 2022Dried blood spot (DBS) is the standard specimen for the newborn screening of inborn errors of metabolism (IEM) by tandem mass spectrometry. Availability of DBS for the...
Dried blood spot (DBS) is the standard specimen for the newborn screening of inborn errors of metabolism (IEM) by tandem mass spectrometry. Availability of DBS for the mass spectrometric analysis of the diagnostic marker proteins, transferrin (Tf) and apolipoprotein CIII (apoCIII), of congenital disorders of glycosylation (CDG) was examined. Recovery of Tf from DBS was only slightly reduced compared with fresh serum. Although oxidation of the core polypeptides was observed, glycans of Tf and apoCIII were unaffected by storage of DBS in the ambient environment for at least 1 month. The combination of DBS and the triple quadrupole mass spectrometer used for IEM screening was sufficient to characterize the aberrant glycoprofiles of Tf and apoCIII in CDG. DBS or dried serum spot on filter paper can reduce the cost of sample transportation and potentially promote mass spectrometric screening of CDG.
PubMed: 36713804
DOI: 10.5702/massspectrometry.A0113 -
Clinical Pharmacokinetics Nov 2014This article discusses dried blood spot (DBS) sampling in therapeutic drug monitoring (TDM). The most important advantages of DBS sampling in TDM are the minimally... (Review)
Review
This article discusses dried blood spot (DBS) sampling in therapeutic drug monitoring (TDM). The most important advantages of DBS sampling in TDM are the minimally invasive procedure of a finger prick (home sampling), the small volume (children), and the stability of the analyte. Many assays in DBS have been reported in the literature over the previous 5 years. These assays and their analytical techniques are reviewed here. Factors that may influence the accuracy and reproducibility of DBS methods are also discussed. Important issues are the correlation with plasma/serum concentrations and the influence of hematocrit on spot size and recovery. The different substrate materials are considered. DBS sampling can be a valid alternative to conventional venous sampling. However, patient correlation studies are indispensable to prove this. Promising developments are dried plasma spots using membrane and hematocrit correction using the potassium concentration.
Topics: Blood Specimen Collection; Dried Blood Spot Testing; Drug Monitoring; Hematocrit; Humans; Immunosuppressive Agents; Netherlands; Plasma; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 25204403
DOI: 10.1007/s40262-014-0177-7 -
Annals of Epidemiology Sep 2020The U.S. response to the SARS-CoV-2 epidemic has been hampered by early and ongoing delays in testing for infection; without data on where infections were occurring and...
PURPOSE
The U.S. response to the SARS-CoV-2 epidemic has been hampered by early and ongoing delays in testing for infection; without data on where infections were occurring and the magnitude of the epidemic, early public health responses were not data-driven. Understanding the prevalence of SARS-CoV-2 infections and immune response is critical to developing and implementing effective public health responses. Most serological surveys have been limited to localities that opted to conduct them and/or were based on convenience samples. Moreover, results of antibody testing might be subject to high false positive rates in the setting of low prevalence of immune response and imperfect test specificity.
METHODS
We will conduct a national serosurvey for SARS-CoV-2 PCR positivity and immune experience. A probability sample of U.S. addresses will be mailed invitations and kits for the self-collection of anterior nares swab and finger prick dried blood spot specimens. Within each sampled household, one adult 18 years or older will be randomly selected and asked to complete a questionnaire and to collect and return biological specimens to a central laboratory. Nasal swab specimens will be tested for SARS-CoV-2 RNA by RNA PCR; dried blood spot specimens will be tested for antibodies to SARS-CoV-2 (i.e., immune experience) by enzyme-linked immunoassays. Positive screening tests for antibodies will be confirmed by a second antibody test with different antigenic basis to improve predictive value of positive (PPV) antibody test results. All persons returning specimens in the baseline phase will be enrolled into a follow-up cohort and mailed additional specimen collection kits 3 months after baseline. A subset of 10% of selected households will be invited to participate in full household testing, with tests offered for all household members aged ≥3 years. The main study outcomes will be period prevalence of infection with SARS-CoV-2 and immune experience, and incidence of SARS-CoV-2 infection and antibody responses.
RESULTS
Power calculations indicate that a national sample of 4000 households will facilitate estimation of national SARS-CoV-2 infection and antibody prevalence with acceptably narrow 95% confidence intervals across several possible scenarios of prevalence levels. Oversampling in up to seven populous states will allow for prevalence estimation among subpopulations. Our 2-stage algorithm for antibody testing produces acceptable PPV at prevalence levels ≥1.0%. Including oversamples in states, we expect to receive data from as many as 9156 participants in 7495 U.S. households.
CONCLUSIONS
In addition to providing robust estimates of prevalence of SARS-CoV-2 infection and immune experience, we anticipate this study will establish a replicable methodology for home-based SARS-CoV-2 testing surveys, address concerns about selection bias, and improve positive predictive value of serology results. Prevalence estimates of SARS-CoV-2 infection and immune experience produced by this study will greatly improve our understanding of the spectrum of COVID-19 disease, its current penetration in various demographic, geographic, and occupational groups, and inform the range of symptoms associated with infection. These data will inform resource needs for control of the ongoing epidemic and facilitate data-driven decisions for epidemic mitigation strategies.
Topics: Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Clinical Trial Protocols as Topic; Coronavirus; Coronavirus Infections; Disease Outbreaks; Humans; Pandemics; Pneumonia, Viral; RNA, Viral; SARS-CoV-2
PubMed: 32791199
DOI: 10.1016/j.annepidem.2020.07.015 -
Mass Spectrometry Reviews Jul 2020Recent advancements in the sensitivity of chemical instrumentation have led to increased interest in the use of microsamples for translational and biomedical research.... (Review)
Review
Recent advancements in the sensitivity of chemical instrumentation have led to increased interest in the use of microsamples for translational and biomedical research. Paper substrates are by far the most widely used media for biofluid collection, and mass spectrometry is the preferred method of analysis of the resultant dried blood spot (DBS) samples. Although there have been a variety of review papers published on DBS, there has been no attempt to unify the century old DBS methodology with modern applications utilizing modified paper and paper-based microfluidics for sampling, storage, processing, and analysis. This critical review will discuss how mass spectrometry has expanded the utility of paper substrates from sample collection and storage, to direct complex mixture analysis to on-surface reaction monitoring.
Topics: Animals; Dried Blood Spot Testing; Equipment Design; Humans; Lab-On-A-Chip Devices; Mass Spectrometry; Specimen Handling
PubMed: 31491055
DOI: 10.1002/mas.21601 -
PloS One 2020Plasma is considered the gold standard for HIV viral load (VL) testing, however its use is challenging due to the need for phlebotomy and centrifugation services, as...
INTRODUCTION
Plasma is considered the gold standard for HIV viral load (VL) testing, however its use is challenging due to the need for phlebotomy and centrifugation services, as well as cold chain for transporting to laboratories for testing. The use of Dried Blood Spot (DBS) specimen has allowed a rapid expansion of antiretroviral therapy (ART) monitoring in remote areas in many African countries, however, the VL in DBS may overestimate the copies of viral RNA result at the clinically relevant range of 1000 copies/ml, due to proviral DNA and intracellular RNA. The characteristics of the cobas® Plasma Separation Card (PSC) specimen are similar to fresh plasma (gold standard), so a better performance of HIV VL is expetected in PSC specimen and can be an alternative to DBS. This study aims to evaluate the performance of cobas® PSC for VL testing at primary health care facilities in Mozambique.
METHODOLOGY
HIV-1 infected adults on ART were enrolled consecutively in two health facilities in Mozambique, between August 2018 and October 2018. Capillary and venous cobas® PSC, DBS and fresh plasma specimens were collected from each patient. All specimens were tested for VL using CAP/CTM v2.0. Sensitivity and specificity of viral load using DBS, capillary and venous PSC specimens were estimated. Viral load obtained in fresh plasma specimen was used as reference and a threshold of 1000 copies/ml was considered for the analyses.
RESULTS
From the total 613 patients included for the study, 2444 specimens including DBS (613), plasma (613), venous cobas® PSC (609) and capillary cobas® PSC (609) were collected and 2407 results were obtained. Sensitivity and specificity of the VL using venous cobas®PSC specimen at 1000 copies/ml threshold were 99.8% and 98.1% respectively, whereas for capillary cobas® PSC sensitivity was 99.6% and specificity was 97.2%. For DBS VL, sensitivity was 96.9% and specificity was 81.8%. Misclassification rate was more prominent in DBS specimens (5.9%), but lower in venous and capillary cobas®PSC with a rate of 0.3% and 0.7% respectively.
CONCLUSION
The cobas® PSC specimen has improved performance over DBS for more accurate VL testing aligned with plasma testing. The use of this specimen type can increase the rates of reliable VL results and this will improve the quality of VL monitoring of HIV-positive patients in low-income settings.
Topics: Adolescent; Adult; Blood Specimen Collection; Cross-Sectional Studies; Female; HIV-1; Humans; Male; Middle Aged; Primary Health Care; Viral Load; Young Adult
PubMed: 32374748
DOI: 10.1371/journal.pone.0232122 -
International Journal of Molecular... Dec 2022Miniaturisation and simplification are novel approaches in clinical bioanalysis, especially in therapeutic drug monitoring (TDM). These contemporary trends are related... (Review)
Review
Miniaturisation and simplification are novel approaches in clinical bioanalysis, especially in therapeutic drug monitoring (TDM). These contemporary trends are related to the sampling, pre-treatment, and analysis of biological fluids. Currently, dried blood spot (DBS), one of the most popular microsampling techniques, is feasible and inexpensive. However, obtaining reliable results with sample homogeneity and volume variability is difficult. Volumetric Absorptive Microsampling (VAMS) has recently enabled the accurate and precise collection of a fixed blood volume. It reduced the hematocrit effect, improved volumetric accuracy, and generated results correlating with the dose and drug exposure from wet blood. This review focuses on VAMS-Mitra™ devices, which have become increasingly important since 2014, mainly for TDM and toxicology studies. First, the current literature has been reviewed based on immunosuppressants and their determination in samples obtained using Mitra™. Second, the critical points, weaknesses, and strengths have been characterized in contrast to classic venipuncture and other microsampling methods. Finally, we indicate the points of attention according to the perspective of Mitra™ as well as its usefulness in clinical practice. VAMS is currently state-of-the-art in microsampling and seems to be a good instrument for improving adherence to immunosuppressive therapy, especially in the pediatric population.
Topics: Humans; Child; Blood Specimen Collection; Drug Monitoring; Dried Blood Spot Testing; Specimen Handling; Immunosuppressive Agents
PubMed: 36614123
DOI: 10.3390/ijms24010681 -
Journal of Acquired Immune Deficiency... Mar 2022Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood.
METHODS
Standard databases (PubMed and Medline), conferences, and gray literature were searched until January 2019. The quality of evidence was evaluated using the Standards for Reporting Studies of Diagnostic Accuracy and Quality Assessment of Diagnostic Accuracy Studies-2 criteria. We used univariate and bivariate random effects models to determine misclassification, sensitivity, and specificity across multiple thresholds, overall and for each viral load technology, and to account for between-study variation.
RESULTS
We identified 23 studies for inclusion in the systematic review that compared the diagnostic accuracy of dried plasma spots with that of plasma. Primary data from 16 of the 23 studies were shared and included in the meta-analysis, representing 18 countries, totaling 1847 paired dried plasma spot:plasma data points. The mean bias of dried plasma spot specimens compared with that of plasma was 0.28 log10 copies/mL, whereas the difference in median viral load was 2.25 log10 copies/mL. More dried plasma spot values were undetectable compared with plasma values (43.6% vs. 29.8%). Analyzing all technologies together, the sensitivity and specificity of dried plasma spot specimens were >92% across all treatment failure thresholds compared and total misclassification <5.4% across all treatment failure thresholds compared. Some technologies had lower sensitivity or specificity; however, the results were typically consistent across treatment failure thresholds.
DISCUSSION
Overall, dried plasma spot specimens performed relatively well compared with plasma with sensitivity and specificity values greater than 90% and misclassification rates less than 10% across all treatment failure thresholds reviewed.
Topics: Dried Blood Spot Testing; HIV Infections; HIV-1; Humans; RNA, Viral; Sensitivity and Specificity; Treatment Failure; Viral Load
PubMed: 34732684
DOI: 10.1097/QAI.0000000000002855 -
International Journal of Biomaterials 2021Amnion grafts can be preserved as freeze-dried amnion membrane (FD-AM) and amnion sponge. Preserved grafts require to be sterilized by gamma irradiation. However, each...
BACKGROUND
Amnion grafts can be preserved as freeze-dried amnion membrane (FD-AM) and amnion sponge. Preserved grafts require to be sterilized by gamma irradiation. However, each step of the process could affect its biological properties. Even so, there are only a few studies that report the influence of the preservation method and gamma irradiation on growth factor levels in preserved amniotic grafts.
METHODS
This was an experimental study with a pretest-posttest group design using a consecutive sampling technique in one batch of amnion donors at a particular time. The amnion was made into FD-AM and amnion sponge preparations, and they were sterilized with gamma irradiation (15 kGy and 25 kGy). Nonirradiated specimens served as controls, and 20 mg of each specimen was pulverized to evaluate the growth factors levels using ELISA.
RESULTS
There were significant decreases in amnion sponge compared to the FD-AM, both in transforming growth factor beta (TGF-) and basic fibroblast growth factor (bFGF) levels and in the preirradiated and 25 kGy postirradiated preparations ( ≤ 0.05). The growth factor levels in the preirradiated and postirradiated FD-AM (both 15 kGy and 25 kGy) showed significant differences ( ≤ 0.05). Likewise, the preirradiated amnion sponge group's growth factor levels compared with the postirradiated amnion sponge group also showed a significant decrease ( ≤ 0.05).
CONCLUSION
TGF- and bFGF levels were lower in amnion sponge than FD-AM. The FD-AM and amnion sponge preparations' growth factors levels were reduced following gamma irradiation sterilization. Although the decrease in growth factor levels is significant, the number of growth factor levels is still sufficient for tissue healing.
PubMed: 33927767
DOI: 10.1155/2021/6685225 -
Bioanalysis Sep 2018We tested a large set (n = 181) of wet urine and dried urine samples spotted on regular cosmetic cotton swabs for comparative UHPLC-MS/MS analysis of various...
AIM
We tested a large set (n = 181) of wet urine and dried urine samples spotted on regular cosmetic cotton swabs for comparative UHPLC-MS/MS analysis of various metabolites across a wide polarity and structural range. Results/methodology: The agreement of measurements between conventional 24 h urines and dried urine spots made from them in situ was evaluated by Passing-Bablok regression and Bland-Altman analysis after creatinine correction. There was full agreement in qualitative results but quantitative analysis revealed underestimation of dried urine spots in some cases. The dried urine samples contained analytes at measurable levels for at least 9 months.
CONCLUSION
Although this technique seems very promising more methodological studies have to be conducted in order to improve applicability of dried urine microvolume fluidic sampling for quantitative analysis.
Topics: Adult; Aged; Calibration; Chromatography, High Pressure Liquid; Creatinine; Female; Healthy Volunteers; Humans; Male; Metabolomics; Middle Aged; Specimen Handling; Tandem Mass Spectrometry; Time Factors; Urinalysis; Young Adult
PubMed: 30088416
DOI: 10.4155/bio-2018-0042 -
Advanced Science (Weinheim,... Sep 2021Blood cell analysis is a major pillar of biomedical research and healthcare. These analyses are performed in central laboratories. Rapid shipment from collection site to...
Blood cell analysis is a major pillar of biomedical research and healthcare. These analyses are performed in central laboratories. Rapid shipment from collection site to the central laboratories is currently needed because cells and biomarkers degrade rapidly. The dried blood spot from a fingerstick allows the preservation of cellular molecules for months but entire cells are never recovered. Here leucocyte elution is optimized from dried blood spots. Flow cytometry and mRNA expression profiling are used to analyze the recovered cells. 50-70% of the leucocytes that are dried on a polyester solid support via elution after shaking the support with buffer are recovered. While red blood cells lyse upon drying, it is found that the majority of leucocytes are preserved. Leucocytes have an altered structure that is improved by adding fixative in the elution buffer. Leucocytes are permeabilized, allowing an easy staining of all cellular compartments. Common immunophenotyping and mRNAs are preserved. The ability of a new biomarker (CD169) to discriminate between patients with and without Severe Acute Respiratory Syndrome induced by Coronavirus 2 (SARS-CoV-2) infections is also preserved. Leucocytes from blood can be dried, shipped, and/or stored for at least 1 month, then recovered for a wide variety of analyses, potentially facilitating biomedical applications worldwide.
Topics: Antibodies, Viral; Biomarkers; Blood Specimen Collection; COVID-19; Cell Separation; Communicable Diseases; Diagnostic Tests, Routine; Dried Blood Spot Testing; Erythrocytes; Flow Cytometry; Hematology; Humans; Immunophenotyping; Leukocytes; RNA, Messenger; SARS-CoV-2
PubMed: 34278739
DOI: 10.1002/advs.202100323