{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:42:20Z","timestamp":1787614940178,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indonesian Endowment Fund for Education (LPDP) of the Ministry of Higher Education, Science, and Technology","award":["4303\/B3\/DT.03.08\/2025"],"award-info":[{"award-number":["4303\/B3\/DT.03.08\/2025"]}]},{"name":"Indonesian Endowment Fund for Education (LPDP) of the Ministry of Higher Education, Science, and Technology","award":["3927\/UN6.RKT\/HK.07.00\/2025"],"award-info":[{"award-number":["3927\/UN6.RKT\/HK.07.00\/2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Accurate malaria diagnosis is essential for effective case management and transmission control; however, the sensitivity, operational requirements, and field applicability of current conventional methods are limited. Hemozoin, an optically and magnetically active crystalline biomarker produced by Plasmodium species, offers a reagent-free target for next-generation diagnostics. This scoping review, following PRISMA-ScR and Joanna Briggs Institute guidance, synthesizes recent advances in hemozoin-based detection technologies and maps the current landscape. Twenty-four studies were reviewed, spanning eight major technology classes: magneto-optical platforms, magnetophoretic microdevices, photoacoustic detection, Raman\/SERS spectroscopy, optical and hyperspectral imaging, NMR relaxometry, smartphone-based microscopy, and flow cytometry. Magneto-optical systems\u2014including Hz-MOD, Gazelle\u2122, and RMOD\u2014demonstrated the highest operational readiness, with robust specificity but reduced sensitivity at low parasitemia. Photoacoustic Cytophone studies demonstrated promising sensitivity and noninvasive in vivo detection. Raman\/SERS platforms achieved sub-100 infected cell\/mL analytical sensitivity but remain laboratory-bound. Microfluidic and smartphone-based tools offer emerging, potentially low-cost alternatives. Across modalities, performance varied by parasite stage, with reduced detection of early ring forms. In conclusion, hemozoin-targeted diagnostics represent a rapidly evolving field with multiple viable translational pathways. While magneto-optical devices are closest to field deployment, further clinical validation, improved low-density detection, and standardized comparison across platforms are needed to support future adoption in malaria-endemic settings.<\/jats:p>","DOI":"10.3390\/bios16010048","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T11:46:43Z","timestamp":1767786403000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hemozoin as a Diagnostic Biomarker: A Scoping Review of Next-Generation Malaria Detection Technologies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8809-0810","authenticated-orcid":false,"given":"Afiat","family":"Berbudi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Parasitology Division, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia"},{"name":"Research Center for Care and Control of Infectious Diseases (RC3ID), Universitas Padjadjaran, Bandung 40161, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-1388","authenticated-orcid":false,"given":"Shafia","family":"Khairani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cell Biology Division, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia"},{"name":"Veterinary Medicine Program, Faculty of Medicine, Universitas Padjadjaran, Sumedang 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0893-2908","authenticated-orcid":false,"given":"Alexander","family":"Kwarteng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5837-3967","authenticated-orcid":false,"given":"Ngozi Mirabel","family":"Otuonye","sequence":"additional","affiliation":[{"name":"Central Research Laboratory, Nigerian Institute of Medical Research, Yaba, Lagos P.O. Box P.M.B. 2013, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Orb\u00e1n, \u00c1., Butykai, \u00c1., Moln\u00e1r, A., Pr\u00f6hle, Z., F\u00fcl\u00f6p, G., Zelles, T., Forsyth, W., Hill, D., M\u00fcller, I., and Schofield, L. (2014). Evaluation of a Novel Magneto-Optical Method for the Detection of Malaria Parasites. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096981"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41427-023-00516-6","article-title":"Hemozoin in malaria eradication\u2014From material science, technology to field test","volume":"15","author":"Rathi","year":"2023","journal-title":"NPG Asia Mater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/1475-2875-13-147","article-title":"Limitations of haemozoin-based diagnosis of Plasmodium falciparum using dark-field microscopy","volume":"13","author":"Delahunt","year":"2014","journal-title":"Malar. J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Baptista, V., Peng, W.K., Minas, G., Veiga, M.I., and Catarino, S.O. (2022). Review of microdevices for hemozoin-based malaria detection. Biosensors, 12.","DOI":"10.3390\/bios12020110"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e29930","DOI":"10.1016\/j.heliyon.2024.e29930","article-title":"Adaptation of the Technology Readiness Levels for impact assessment in implementation sciences: The TRL-IS checklist","volume":"10","author":"Woods","year":"2024","journal-title":"Heliyon"},{"key":"ref_6","first-page":"1997","article-title":"Adopting Technologies in Medical and Healthcare Systems","volume":"13","author":"Mahendrakar","year":"2025","journal-title":"Int. J. Sci. Technol. Eng."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12936-021-03688-0","article-title":"Performance of a sensitive haemozoin-based malaria diagnostic test validated for vivax malaria diagnosis in Brazilian Amazon","volume":"20","author":"Melo","year":"2021","journal-title":"Malar. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s12936-022-04283-7","article-title":"Evaluation of a haemozoin-based rapid diagnostic test for diagnosis of imported malaria during the phase of prevention of reestablishment in Sri Lanka","volume":"21","author":"Fernando","year":"2022","journal-title":"Malar. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4760","DOI":"10.1038\/s41598-023-31839-7","article-title":"Evaluation of a point-of-care haemozoin assay (Gazelle device) for rapid detection of Plasmodium knowlesi malaria","volume":"13","author":"Tan","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/20477724.2025.2551508","article-title":"Diagnostic performance of hemozoin-based magneto-optical detection assay and RDT: A prospective observational study","volume":"119","author":"Nallapati","year":"2025","journal-title":"Pathog. Glob. Health"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fontecha, G., Escobar, D., Ortiz, B., Pinto, A., Serrano, D., and Valdivia, H.O. (2022). Field Evaluation of a Hemozoin-Based Malaria Diagnostic Device in Puerto Lempira, Honduras. Diagnostics, 12.","DOI":"10.3390\/diagnostics12051206"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18547","DOI":"10.1038\/s41598-021-97532-9","article-title":"Sensitive detection of Plasmodium vivax malaria by the rotating-crystal magneto-optical method in Thailand","volume":"11","author":"Longley","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/s41467-021-21110-w","article-title":"Magneto-optical diagnosis of symptomatic malaria in Papua New Guinea","volume":"12","author":"Arndt","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_14","first-page":"60988","article-title":"Magneto-optical assessment of Plasmodium parasite growth via hemozoin crystal size","volume":"14","author":"Zelles","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2004101","DOI":"10.1002\/advs.202004101","article-title":"A Lab-On-chip Tool for Rapid, Quantitative, and Stage-selective Diagnosis of Malaria","volume":"8","author":"Giacometti","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8671","DOI":"10.1038\/s41598-022-11452-w","article-title":"Towards rainbow portable Cytophone with laser diodes for global disease diagnostics","volume":"12","author":"Jawad","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9228","DOI":"10.1038\/s41467-024-53243-z","article-title":"Noninvasive in vivo photoacoustic detection of malaria with Cytophone in Cameroon","volume":"15","author":"Yadem","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1021\/acs.jpclett.1c03873","article-title":"Selenium Vacancies and Synergistic Effect of Near- and Far-Field-Enabled Ultrasensitive Surface-Enhanced Raman-Scattering-Active Substrates for Malaria Detection","volume":"13","author":"Xu","year":"2022","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"464318","DOI":"10.1016\/j.chroma.2023.464318","article-title":"A magnetic field augmented ultra-thin layer chromatography coupled surface enhanced Raman spectroscopy separation of hemozoin from bacterial mixture","volume":"1708","author":"Yadav","year":"2023","journal-title":"J. Chromatogr. A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4972","DOI":"10.1039\/D5AN00272A","article-title":"Two-dimensional correlation spectroscopy (2D-COS) in the analysis of parasitemia in Raman spectra of red blood cells of patients diagnosed with malaria","volume":"150","author":"Migdalski","year":"2025","journal-title":"Analyst"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/acsinfecdis.2c00484","article-title":"Optical Spectrophotometry as a Promising Method for Quantification and Stage Differentiation of Plasmodium falciparum Parasites","volume":"9","author":"Baptista","year":"2023","journal-title":"ACS Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"023516","DOI":"10.1117\/1.JBO.30.2.023516","article-title":"Hyperspectral analysis to assess gametocytogenesis stage progression in malaria-infected human erythrocytes","volume":"30","author":"Kwon","year":"2025","journal-title":"J. Biomed. Opt."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5200211","DOI":"10.1109\/TMAG.2021.3096046","article-title":"An ON-OFF Magneto-Optical Probe of Anisotropic Biofluid Crystals: A \u03b2-Hematin Case Study","volume":"57","author":"Kara","year":"2021","journal-title":"IEEE Trans. Magn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3366","DOI":"10.1002\/mrm.28387","article-title":"Relaxometric studies of erythrocyte suspensions infected by Plasmodium falciparum: A tool for staging infection and testing anti-malarial drugs","volume":"84","author":"Ferrauto","year":"2020","journal-title":"Magn. Reson. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e202200290","DOI":"10.1002\/jbio.202200290","article-title":"A high-performance cell-phone based polarized microscope for malaria diagnosis","volume":"16","author":"Yu","year":"2023","journal-title":"J. Biophotonics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1111\/ijlh.13522","article-title":"A false-negative rapid diagnostic malaria test and white blood cell inclusions in a patient with severe Plasmodium falciparum infection","volume":"43","author":"Eeckhout","year":"2021","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6882","DOI":"10.1038\/s41467-022-34678-8","article-title":"The Prognostic and Diagnostic Value of Intraleukocytic Malaria Pigment in Patients with Severe Falciparum Malaria: An Individual Patient Data Meta-Analysis","volume":"13","author":"Srinamon","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Pance, A., Ng, B.L., Mwikali, K., Koutsourakis, M., Agu, C., Rouhani, F.J., Montandon, R., Law, F., Ponstingl, H., and Rayner, J.C. (2023). Novel stem cell technologies are powerful tools to understand the impact of human factors on Plasmodium falciparum malaria. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1287355"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7741","DOI":"10.1039\/D0AN00976H","article-title":"Rapid quantification of the malaria biomarker hemozoin by improved biocatalytically initiated precipitation atom transfer radical polymerizations","volume":"145","author":"Raccio","year":"2020","journal-title":"Analyst"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"123902","DOI":"10.1016\/j.saa.2024.123902","article-title":"Hematin anhydride (\u03b2-hematin): An analogue to malaria pigment hemozoin possesses nonlinearity","volume":"310","author":"Sahoo","year":"2024","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1186\/1475-2875-10-321","article-title":"Systematic review and meta-analysis: Rapid diagnostic tests versus placental histology, microscopy and PCR for malaria in pregnant women","volume":"10","author":"Kattenberg","year":"2011","journal-title":"Malar. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12936-023-04506-5","article-title":"Accuracy of diagnosis among clinical malaria patients: Comparing microscopy, RDT and a highly sensitive quantitative PCR looking at the implications for submicroscopic infections","volume":"22","author":"Addison","year":"2023","journal-title":"Malar. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1529\/biophysj.107.128140","article-title":"A magneto-optic route toward the in vivo diagnosis of malaria: Preliminary results and preclinical trial data","volume":"95","author":"Newman","year":"2008","journal-title":"Biophys. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5800","DOI":"10.1364\/BOE.401771","article-title":"Quantitative diffuse optical spectroscopy for noninvasive measurements of the malaria pigment hemozoin","volume":"11","author":"Campbell","year":"2020","journal-title":"Biomed. Opt. Express"},{"key":"ref_35","first-page":"1045304","article-title":"Spectrophotometric characterization of hemozoin as a malaria biomarker","volume":"10453","author":"Catarino","year":"2017","journal-title":"Proc. SPIE"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1039\/b822603b","article-title":"Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics","volume":"134","author":"Wood","year":"2009","journal-title":"Analyst"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"572","DOI":"10.4269\/ajtmh.18-0773","article-title":"Plasmodium falciparum Gametocyte Enrichment in Peripheral Blood Samples by Magnetic Fractionation: Gametocyte Yields and Possibilities to Reuse Columns","volume":"100","author":"Graumans","year":"2019","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_38","first-page":"118","article-title":"Hemozoin detection in malaria-infected erythrocytes and leukocytes by flow cytometry","volume":"69","author":"Moore","year":"2006","journal-title":"Cytom. Part A"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Saha, R.K., Karmakar, S., and Roy, M. (2012, January 7\u201310). A Monte Carlo study on intraerythrocytic staging of malaria parasite using photoacoustics. Proceedings of the IEEE International Ultrasonics Symposium, Dresden, German.","DOI":"10.1109\/ULTSYM.2012.0582"},{"key":"ref_40","first-page":"332","article-title":"Photoacoustic detection of hemozoin in human mononuclear cells as an early indicator of malaria infection","volume":"7564","author":"Custer","year":"2010","journal-title":"Bios"},{"key":"ref_41","first-page":"967","article-title":"Analysis of malaria diagnosis discrepancies between RDTs and microscopy by nested PCR","volume":"2013","author":"Mbouoronde","year":"2013","journal-title":"J. Biomed. Sci. Eng."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/s12936-016-1393-4","article-title":"Common asymptomatic and submicroscopic malaria infections in Western Thailand revealed in longitudinal molecular and serological studies: A challenge to malaria elimination","volume":"15","author":"Baum","year":"2016","journal-title":"Malar. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/0035-9203(95)90496-4","article-title":"Intraleucocytic Malaria Pigment and Prognosis in Severe Malaria","volume":"89","author":"Nguyen","year":"1995","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Milesi, F., Giacometti, M., Coppadoro, L.P., Ferrari, G., Fiore, G.B., and Bertacco, R. (2020). On-Chip Selective Capture and Detection of Magnetic Fingerprints of Malaria. Sensors, 20.","DOI":"10.3390\/s20174972"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1364\/BOE.6.003462","article-title":"In vivo microscopy of hemozoin: Towards a needle free diagnostic for malaria","volume":"6","author":"Burnett","year":"2015","journal-title":"Biomed. Opt. Express"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3347\/kjp.2016.54.4.393","article-title":"Hemozoin Pigment: An Important Tool for Low Parasitemic Malarial Diagnosis","volume":"54","author":"Mohapatra","year":"2016","journal-title":"Korean J. Parasitol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1186\/s12936-017-2096-1","article-title":"Towards a needle-free diagnosis of malaria: In vivo identification and classification of red and white blood cells containing haemozoin","volume":"16","author":"Burnett","year":"2017","journal-title":"Malar. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e0099424","DOI":"10.1128\/spectrum.00994-24","article-title":"Slow clearance of histidine-rich protein-2 in Gabonese with uncomplicated malaria","volume":"12","author":"Schaumburg","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"43663","DOI":"10.1038\/s41598-025-97259-x","article-title":"Performance and Challenges of Malaria Rapid Diagnostic Tests in Endemic Regions of Africa","volume":"15","author":"Ojeniyi","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1186\/1475-2875-8-255","article-title":"Is flow cytometry better in counting malaria pigment-containing leukocytes compared to microscopy?","volume":"8","author":"Frita","year":"2009","journal-title":"Malar. J."}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/16\/1\/48\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T12:02:03Z","timestamp":1767787323000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/16\/1\/48"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["bios16010048"],"URL":"https:\/\/doi.org\/10.3390\/bios16010048","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]}}}