Paper-based microchip electrophoresis for point-of-care hemoglobin testing

Hasan, Mahmud; Fraiwan, Arwa; An, Ran; Alapan, Yunus; Ung, Ryan; Akkus, Asya; Xu, Julia; Rezac, Amy J.; Kocmich, Nicholas; Creary, Melissa S.; Oginni, Tolulope; Olanipekun, Grace; Hassan-Hanga, Fatimah; Jibir, Binta W.; Gambo, Safiya; Verma, Anil; Bharti, Praveen K.; Riolueang, Suchada; Ngimhung, Takdanai; Suksangpleng, Thidarat; Thota, Priyaleela; Werner, Greg; Shanmugam, Rajasubramaniam; Das, Ashim; Viprakasit, Vip; Piccone, Connie M.; Little, Jane A.; Obaro, Stephen K.; Gürkan, Umut A.

doi:10.1039/c9an02250c

Cited by 51 publications

(65 citation statements)

References 98 publications

(153 reference statements)

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“…A microchip electrophoresis paper-based has been developed to identify and quantify hemoglobin types, including HbA, A2, F, S, and C [ 90 ]. This microchip is named HemeChip platform, and it consists of a cartridge where the hemoglobin variants are isolated, pictured, and tracked during electrophoresis.…”

Section: Innovative Techniques For the Diagnosis And Monitoring Of Scdmentioning

confidence: 99%

“…This microchip is named HemeChip platform, and it consists of a cartridge where the hemoglobin variants are isolated, pictured, and tracked during electrophoresis. HemeChip is based on separating the hemoglobin using cellulose acetate electrophoresis [ 18 , 90 ]. The HemeChip test is performed by mixing the blood sample with deionized water, and then the microchip is placed inside the HemeChip reader and an electrical field is applied, which results in separating the Hb.…”

Section: Innovative Techniques For the Diagnosis And Monitoring Of Scdmentioning

confidence: 99%

“…As a result, each Hb moves a unique distance across the paper strip. Real-time images are taken during the test and analyzed automatically using custom built-in software [ 90 ]. This test has a number of advantages such as low-cost, disposable, portable, high accuracy, easy to perform, and can be completed in less than 10 min [ 18 ].…”

Section: Innovative Techniques For the Diagnosis And Monitoring Of Scdmentioning

confidence: 99%

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Techniques for the Detection of Sickle Cell Disease: A Review

2021

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Sickle cell disease (SCD) is a widespread disease caused by a mutation in the beta-globin gene that leads to the production of abnormal hemoglobin called hemoglobin S. The inheritance of the mutation could be homozygous or heterozygous combined with another hemoglobin mutation. SCD can be characterized by the presence of dense, sickled cells that causes hemolysis of blood cells, anemia, painful episodes, organ damage, and in some cases death. Early detection of SCD can help to reduce the mortality and manage the disease effectively. Therefore, different techniques have been developed to detect the sickle cell disease and the carrier states with high sensitivity and specificity. These techniques can be screening tests such as complete blood count, peripheral blood smears, and sickling test; confirmatory tests such as hemoglobin separation techniques; and genetic tests, which are more expensive and need to be done in centralized labs by highly skilled personnel. However, advanced portable point of care techniques have been developed to provide a low-cost, simple, and user-friendly device for detecting SCD, for instance coupling solubility tests with portable devices, using smartphone microscopic classifications, image processing techniques, rapid immunoassays, and sensor-based platforms. This review provides an overview of the current and emerging techniques for sickle cell disease detection and highlights the different potential methods that could be applied to help the early diagnosis of SCD.

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Section: Innovative Techniques For the Diagnosis And Monitoring Of Scdmentioning

confidence: 99%

Section: Innovative Techniques For the Diagnosis And Monitoring Of Scdmentioning

confidence: 99%

Section: Innovative Techniques For the Diagnosis And Monitoring Of Scdmentioning

confidence: 99%

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Techniques for the Detection of Sickle Cell Disease: A Review

2021

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“…Altered RBC rheology is a major contributor to the clinical manifestations of SCD. Sickle cell disease is a recessively inherited beta‐globin gene disorder, 9 in which abnormal hydrophobic hemoglobin, HbS, 4,10 polymerizes into long and stiff intracellular structures under certain physiologic conditions (eg, dehydration and deoxygenation). Abnormal HbS polymerization ultimately leads to the formation of sickle‐shaped and excessively stiff RBCs 11,12 .…”

Section: Introductionmentioning

confidence: 99%

Standardized microfluidic assessment of red blood cell–mediated microcapillary occlusion: Association with clinical phenotype and hydroxyurea responsiveness in sickle cell disease

Man

Kucukal

et al. 2021

Microcirculation

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Objectives We present a standardized in vitro microfluidic assay and Occlusion Index (OI) for the assessment of red blood cell (RBC)–mediated microcapillary occlusion and its clinical associations in sickle cell disease (SCD). Methods Red blood cell mediated microcapillary occlusion represented by OI and its clinical associations were assessed for seven subjects with hemoglobin‐SC disease (HbSC), 18 subjects with homozygous SCD (HbSS), and five control individuals (HbAA). Results We identified two sub‐populations with HbSS based on the OI distribution. HbSS subjects with relatively higher OIs had significantly lower hemoglobin levels, lower fetal hemoglobin (HbF) levels, and lower mean corpuscular volume (MCV), but significantly higher serum lactate dehydrogenase levels and absolute reticulocyte counts, compared to subjects with HbSS and lower OIs. HbSS subjects who had relatively higher OIs were more likely to have had a concomitant diagnosis of intrapulmonary shunting (IPS). Further, lower OI associated with hydroxyurea (HU) responsiveness in subjects with HbSS, as evidenced by significantly elevated HbF levels and MCV. Conclusions We demonstrated that RBC‐mediated microcapillary occlusion and OI associated with subject clinical phenotype and HU responsiveness in SCD. The presented standardized microfluidic assay may be useful for evaluating clinical phenotype and assessing therapeutic outcomes in SCD, including emerging targeted and curative treatments that aim to improve RBC deformability and microcirculatory health.

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“…[ 12 ] Although one of the most studied fields of paper is microfluidic paper‐based analytical devices (μPADs), paper substrates can be used in other applications for point‐of‐care medical diagnostics, such as paper‐based electrochemical detection, [ 13 ] and μPADs can be used for microchip electrophoresis. [ 14 ] Paper substrates have also been successfully applied to fabricate inexpensive SERS substrates and have achieved a good enhancement factor (EF) in the range 10 5 –10 7 . [ 15 ] Recent years have witnessed a growing interest in the application of SERS‐based paper substrates for sensing trace chemicals and bioanalysis.…”

Section: Introductionmentioning

confidence: 99%

Inkjet‐based microreactor for the synthesis of silver nanoparticles on plasmonic paper decorated with chitosan nano‐wrinkles for efficient on‐site Surface‐enhanced Raman Scattering (SERS)

et al. 2020

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Here we report a synthesis approach that is simple, surfactant free, and green, and which is additionally cost effective in terms of its material requirements. The approach entails the use of an inkjet microreactor for the deposition of silver nanoparticles on the surface of office paper decorated with chitosan nano-wrinkles for the preparation of a reproducible and sensitive paper-based surface-enhanced Raman scattering (SERS) substrate. Silver nanoparticles were synthesized directly in the head nozzles of the inkjet printer via the reduction of silver nitrate (AgNO 3) by ascorbic acid. Pre-modification of the paper with chitosan allowed the formation of randomly oriented nano-wrinkles on the surface, thus enabling the formation of silver nanoparticles with good hotspots. The novel paper-based SERS substrate showed outstanding sensitivity and spot-to-spot reproducibility for on-site detection using a portable Raman spectrometer with a limit of detection (LOD) of 10.7 pM. Moreover, our paper-based SERS substrate has an excellent enhancement factor (EF) of 7.4 × 10 8 , which is difficult to achieve on a paper substrate because of the microporous nature of paper. Finally, the batch-to-batch reproducibility and long-term stability of the SERS substrate under ambient conditions make this substrate a good candidate for point-of-care test applications. K E Y W O R D S chitosan, flexible, nano-wrinkles, plasmonic paper, SERS, silver nanoparticles 1 INTRODUCTION Over the last decades, platforms based on nanomaterials and optical measurement techniques, including fluorescence, surface plasmon resonance (SPR), and colorimetry, This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Paper-based microchip electrophoresis for point-of-care hemoglobin testing

Abstract: We present a versatile, mass-producible, paper-based microchip electrophoresis platform that enables rapid, affordable, decentralized hemoglobin testing at the point-of-care.

Cited by 51 publications

References 98 publications

Techniques for the Detection of Sickle Cell Disease: A Review

Techniques for the Detection of Sickle Cell Disease: A Review

Standardized microfluidic assessment of red blood cell–mediated microcapillary occlusion: Association with clinical phenotype and hydroxyurea responsiveness in sickle cell disease

Inkjet‐based microreactor for the synthesis of silver nanoparticles on plasmonic paper decorated with chitosan nano‐wrinkles for efficient on‐site Surface‐enhanced Raman Scattering (SERS)

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