{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:07:07Z","timestamp":1785143227333,"version":"3.55.0"},"reference-count":23,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Capillary blood sampling may improve access to multi-cancer early detection (MCED) by enabling less invasive and more decentralized specimen collection. However, its paired-specimen measurement agreement with conventional venous blood for protein biomarker-based MCED testing requires validation. Objective: The objective of this study was to evaluate agreement between capillary and venous blood specimens for OneTest protein biomarkers and to assess the exact risk category agreement of the OneTest Premium algorithm outputs generated from both specimen types. Methods: This two-stage study compared paired venous and capillary blood specimens. Study 1 enrolled 143 Taiwanese adults undergoing clinically indicated biomarker testing to evaluate paired-specimen measurement agreement. Study 2 involved an exploratory paired-specimen evaluation in 13 asymptomatic U.S. volunteers using an upper arm capillary blood collection device. Biomarker concentrations were compared using paired statistical testing, correlation analysis, and Bland\u2013Altman analysis. OneTest Premium risk categories and cancer type prediction outputs were compared between specimen types. Results: In Study 1, no statistically significant differences were observed between capillary and venous specimens for any evaluated biomarker. Descriptive scatterplots showed strong linear associations between paired capillary and venous biomarker measurements across the observed concentration ranges. Bland\u2013Altman analysis showed mean biases close to zero for most biomarkers, with biomarker-specific limits of agreement. In Study 2, all 12 biomarkers were successfully measured in all 13 participants. OneTest Premium risk categorization was concordant in 11 of 13 participants; discordant cases involved adjacent low-risk and mild-risk categories, with no major or very major classification errors. Given the small sample size, these findings are descriptive and preliminary. Conclusions: Capillary blood specimens showed paired measurement agreement with venous specimens in Study 1. The exploratory findings from Study 2 suggest that capillary-derived measurements may support the generation of OneTest Premium outputs.<\/jats:p>","DOI":"10.3390\/diagnostics16152324","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:53:26Z","timestamp":1784901206000},"page":"2324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paired Capillary and Venous Serum Specimen Agreement for Protein Biomarker Measurements and Risk Category Outputs in a Multi-Cancer Early Detection Tool"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5581-6793","authenticated-orcid":false,"given":"Hsin-Yao","family":"Wang","sequence":"first","affiliation":[{"name":"20\/20 Biolabs, Inc., Gaithersburg, MD 20877, USA"},{"name":"Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan"},{"name":"School of Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"20\/20 Biolabs, Inc., Gaithersburg, MD 20877, USA"},{"name":"Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan"},{"name":"Department of Medicine, University at Buffalo-Catholic Health System, Buffalo, NY 14068, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenfei","family":"Zhou","sequence":"additional","affiliation":[{"name":"20\/20 Biolabs, Inc., Gaithersburg, MD 20877, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer Q. L.","family":"Xu","sequence":"additional","affiliation":[{"name":"20\/20 Biolabs, Inc., Gaithersburg, MD 20877, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zayd","family":"Anwar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Vassar Brothers Medical Center, Poughkeepsie, NY 12601, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3260-4269","authenticated-orcid":false,"given":"Jia-Ruei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Lebowitz","sequence":"additional","affiliation":[{"name":"20\/20 Biolabs, Inc., Gaithersburg, MD 20877, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70075","DOI":"10.1002\/cncr.70075","article-title":"The impact of multicancer early detection tests on cancer stage shift: A 10-year microsimulation model","volume":"131","author":"Chhatwal","year":"2025","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e086648","DOI":"10.1136\/bmjopen-2024-086648","article-title":"Assessment of the impact of multi-cancer early detection test screening intervals on late-stage cancer at diagnosis and mortality using a state-transition model","volume":"15","author":"Rous","year":"2025","journal-title":"BMJ Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41416-023-02243-9","article-title":"Modelled mortality benefits of multi-cancer early detection screening in England","volume":"129","author":"Sasieni","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2449556","DOI":"10.1001\/jamanetworkopen.2024.49556","article-title":"Social Risks and Nonadherence to Recommended Cancer Screening Among US Adults","volume":"8","author":"Sedani","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e200618","DOI":"10.1001\/jamanetworkopen.2020.0618","article-title":"Association of Neighborhood Measures of Social Determinants of Health with Breast, Cervical, and Colorectal Cancer Screening Rates in the US Midwest","volume":"3","author":"Kurani","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e2537905","DOI":"10.1001\/jamanetworkopen.2025.37905","article-title":"Geographic and Temporal Patterns of Screening for Breast, Cervical, and Colorectal Cancer in the US, 1997\u20132019","volume":"8","author":"Pradhan","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, H.Y., Hsieh, C.H., Wen, C.N., Wen, Y.H., Chen, C.H., and Lu, J.J. (2016). Cancers Screening in an Asymptomatic Population by Using Multiple Tumour Markers. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158285"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, H.Y., Chen, C.H., Shi, S., Chung, C.R., Wen, Y.H., Wu, M.H., Lebowitz, M.S., Zhou, J., and Lu, J.J. (2020). Improving Multi-Tumor Biomarker Health Check-Up Tests with Machine Learning Algorithms. Cancers, 12.","DOI":"10.3390\/cancers12061442"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105362","DOI":"10.1016\/j.compbiomed.2022.105362","article-title":"Long short-term memory model\u2014A deep learning approach for medical data with irregularity in cancer predication with tumor markers","volume":"144","author":"Wu","year":"2022","journal-title":"Comput. Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, H.Y., Lin, W.Y., Zhou, C., Yang, Z.A., Kalpana, S., and Lebowitz, M.S. (2024). Integrating Artificial Intelligence for Advancing Multiple-Cancer Early Detection via Serum Biomarkers: A Narrative Review. Cancers, 16.","DOI":"10.20944\/preprints202401.0082.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102041","DOI":"10.1016\/j.eclinm.2023.102041","article-title":"A panel of seven protein tumour markers for effective and affordable multi-cancer early detection by artificial intelligence: A large-scale and multicentre case-control study","volume":"61","author":"Luan","year":"2023","journal-title":"eClinicalMedicine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1126\/science.aar3247","article-title":"Detection and localization of surgically resectable cancers with a multi-analyte blood test","volume":"359","author":"Cohen","year":"2018","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.annonc.2020.02.011","article-title":"Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA","volume":"31","author":"Liu","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/S0140-6736(23)01700-2","article-title":"Blood-based tests for multicancer early detection (PATHFINDER): A prospective cohort study","volume":"402","author":"Schrag","year":"2023","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.ijnurstu.2009.10.001","article-title":"Statistical methods for assessing agreement between two methods of clinical measurement","volume":"47","author":"Bland","year":"2010","journal-title":"Int. J. Nurs. Stud."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1093\/jalm\/jfaf005","article-title":"Evaluation of a Novel Capillary Blood Collection System for Blood Sampling in Nontraditional Settings as Compared with Currently Marketed Capillary and Venous Blood Collection Systems for Selected General Chemistry Analytes","volume":"10","author":"Parikh","year":"2025","journal-title":"J. Appl. Lab. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"eabb9601","DOI":"10.1126\/science.abb9601","article-title":"Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention","volume":"369","author":"Lennon","year":"2020","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2300607","DOI":"10.1002\/pmic.202300607","article-title":"Capillary blood self-collection for high-throughput proteomics","volume":"24","author":"Huang","year":"2024","journal-title":"Proteomics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1515\/cclm-2013-0228","article-title":"Current and future use of \u2018dried blood spot\u2019 analyses in clinical chemistry","volume":"51","author":"Lehmann","year":"2013","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"256","DOI":"10.4269\/ajtmh.17-0889","article-title":"Dried Blood Spots for Global Health Diagnostics and Surveillance: Opportunities and Challenges","volume":"99","author":"Lim","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1309\/AJCP1L7DKMPCHPEH","article-title":"Drop-to-drop variation in the cellular components of fingerprick blood: Implications for point-of-care diagnostic development","volume":"144","author":"Bond","year":"2015","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e000073","DOI":"10.1136\/bmjonc-2023-000073","article-title":"Novel proteomics-based plasma test for early detection of multiple cancers in the general population","volume":"3","author":"Budnik","year":"2024","journal-title":"BMJ Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41698-025-01105-2","article-title":"A large-scale, multi-centre validation study of an AI-empowered blood-based test for multi-cancer early detection","volume":"9","author":"Shen","year":"2025","journal-title":"NPJ Precis. Oncol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/15\/2324\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:25:13Z","timestamp":1785140713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/15\/2324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":23,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["diagnostics16152324"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16152324","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}