A simple, rapid, low-cost diagnostic test for sickle cell disease

Lab on a Chip ◽  
2013 ◽  
Vol 13 (8) ◽  
pp. 1464 ◽  
Author(s):  
Xiaoxi Yang ◽  
Julie Kanter ◽  
Nathaniel Z. Piety ◽  
Melody S. Benton ◽  
Seth M. Vignes ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Diagnostic Test ◽  
Sickle Cell ◽  
Low Cost ◽  
Cell Disease

Label-Free Sickle Cell Disease Diagnosis using a Low-Cost, Handheld Platform

2016 ◽  
Vol 1 (5) ◽  
pp. 1600100 ◽  
Author(s):  
Bekir Yenilmez ◽  
Stephanie Knowlton ◽  
Chu Hsiang Yu ◽  
Matthew M. Heeney ◽  
Savas Tasoglu
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Low Cost ◽  
Disease Diagnosis ◽  
Label Free ◽  
Cell Disease

scholarly journals Evaluation of a Density-Based Rapid Diagnostic Test for Sickle Cell Disease in a Clinical Setting in Zambia

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e114540 ◽  
Author(s):  
Ashok A. Kumar ◽  
Catherine Chunda-Liyoka ◽  
Jonathan W. Hennek ◽  
Hamakwa Mantina ◽  
S. Y. Ryan Lee ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Diagnostic Test ◽  
Rapid Diagnostic Test ◽  
Sickle Cell ◽  
Clinical Setting ◽  
Cell Disease

scholarly journals Disease Diagnostics: Label-Free Sickle Cell Disease Diagnosis using a Low-Cost, Handheld Platform (Adv. Mater. Technol. 5/2016)

2016 ◽  
Vol 1 (5) ◽  
Author(s):  
Bekir Yenilmez ◽  
Stephanie Knowlton ◽  
Chu Hsiang Yu ◽  
Matthew M. Heeney ◽  
Savas Tasoglu
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Low Cost ◽  
Disease Diagnosis ◽  
Label Free ◽  
Cell Disease ◽  
Disease Diagnostics

scholarly journals Assessment of Cerebral Blood Flow and Oxygen Extraction in Pediatric Sickle Cell Disease with Non-Invasive Diffuse Optical Spectroscopies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Seung Yup Lee ◽  
Eashani Sathilingam ◽  
Kyle R. Cowdrick ◽  
Rowan O. Brothers ◽  
Wilbur A. Lam ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Low Cost ◽  
Oxygen Extraction ◽  
Signal Quality ◽  
Cell Disease ◽  
Non Invasive

Introduction: Cerebral infarcts and associated cognitive impairments are a devastating consequence of sickle cell disease (SCD). While the underlying mechanisms are poorly understood, infarctions are thought to arise from anemia-induced microvascular perfusion abnormalities and subsequent reduced cerebrovascular reserve that is insufficient to meet tissue metabolic demands. Thus, quantification of abnormalities in microvascular cerebral blood flow (CBF) and oxygen extraction (OEF) may be useful in identifying infarct risk and monitoring therapeutic efficacy. Unfortunately, current modalities that quantify microvascular hemodynamics (e.g., PET, MRI) are prohibitively expensive, have limited availability, and require anesthesia in children <6y, making them inappropriate as routine monitoring tools. Transcranial Doppler ultrasound (TCD) is currently the standard screening tool for overt stroke risk in pediatric SCD, but it only measures blood flow velocity in the large arteries, which is a poor surrogate for microvascular perfusion in sickle cell disease. Diffuse optical spectroscopies (specifically near-infrared frequency-domain spectroscopy, FDNIRS, and diffuse correlation spectroscopy, DCS) offer a low-cost, non-invasive alternative for bedside monitoring of tissue-level OEF and CBF. We previously demonstrated that FDNIRS/DCS are sensitive to elevations in resting-state OEF and CBF in children with sickle cell disease compared to healthy controls (Lee, Neurophotonics 2019), consistent with previous studies using MRI and PET. In this feasibility study, we demonstrate these optical techniques are sensitive to altered cerebral hemodynamics in sickle patients who are 1) undergoing chronic transfusion, and 2) experiencing vaso-occlusive pain episodes (VOE). Methods: To date, we have recruited 6 pediatric patients with sickle cell disease undergoing chronic transfusion (5 females and 1 male, 6 - 14 y, mean ± std hemoglobin change pre- to post-transfusion = 1 ± 0.8 g/dL) and 4 patients admitted to the Emergency department for VOE (2 females and 2 males, 8 - 18 y, mean±std hemoglobin on admission = 8.9 ± 1.6 g/dL). For the transfusion cohort, FDNIRS/DCS measurements were made immediately prior to the start of transfusion and again immediately upon completion. For the VOE cohort, FDNIRS/DCS measurements were made upon hospital admission. For all FDNIRS/DCS assessments, a custom sensor was manually held over right and left forehead to assess oxygen extraction fraction (OEF, %) and an index of microvascular cerebral blood flow (CBFi, cm2/s) (Lee, Neurophotonics 2019). Hemispheric results were averaged to yield a mean of each measured parameter. Total measurement time was less than 15 minutes. Results: In the cohort undergoing chronic transfusion, one patient data was excluded due to poor DCS signal quality. Of the remaining 5 patients, OEF and CBFi decreased after transfusion by a median of -6.4% and -30.0%, respectively (Fig 1A, B). The FDNIRS-measured OEF decrease is comparable to previous results with MRI (Guilliams, Blood 2017) that quantified both cortical OEF and CBF response to transfusion in a similarly aged cohort. However, the DCS-measured CBFi decrease is more prominent than previously reported (30% vs. 9%). The enhanced sensitivity of DCS to CBF in sickle cell disease was reported in our recent study and is likely attributed to the confounding influences of hematocrit on the DCS-measured CBFi (Sathialingam, Biomed Opt Exp 2020). In the cohort measured during VOE, one patient data was excluded due to poor FDNIRS data quality. Of the remaining 3 subjects, OEF was elevated compared to healthy controls and was on the upper range of values measured in a cohort of otherwise subjects with sickle cell disease who were without clinical complications and were measured as part of a separate study (Fig. 1C). Conclusion: These data demonstrate how FDNIRS/DCS may be used as a simple, low-cost tool for bedside assessment of cerebral hemodynamics in non-sedated sickle children that could be used to track brain health over time, particularly during periods thought to be prone to hemodynamic instability like transfusion or VOEs. Although ~20% of data was discarded in this dataset due to improper sensor positioning leading to poor signal quality, we have recently implemented real-time quality control feedback to ensure our data passes quality criteria. Disclosures Lam: Sanguina, Inc: Current equity holder in private company.

Initial Clinical Validation of a Rapid, Low-Cost, Paper-Based Diagnostic Test for Sickle Cell Anemia As a Tool to Facilitate Newborn Screening in Resource-Limited Settings

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 979-979
Author(s):  
Nathaniel Z. Piety ◽  
Alex George ◽  
Sonia Serrano ◽  
Maria Rosa Lanzi ◽  
Palka R. Patel ◽  
...  
Keyword(s):  
High Risk ◽  
Sickle Cell Disease ◽  
Newborn Screening ◽  
Diagnostic Test ◽  
Sickle Cell ◽  
Rapid Test ◽  
Cell Disease ◽  
Blood Samples ◽  
Resource Limited ◽  
Application Paper

Abstract Newborn screening for sickle cell disease (SCD) in developing countries is limited by the cost and technical complexity of current screening methodologies and the delayed availability of screening results. We have recently developed a rapid diagnostic test for SCD that can quickly and inexpensively identify blood samples containing hemoglobin S. We hypothesized that our rapid test would be practical for use in a resource-limited setting in Cabinda, Angola, and that screening mothers or neonates for the presence of hemoglobin S in blood samples would be an effective means of identifying neonates at high risk of having sickle cell disease prior to more definitive testing. After informed consent, we collected blood samples heel-stick from neonates and by finger-stick from mothers at the primary obstetric hospital in Cabinda. We then tested these samples by the rapid SCD test and scored them by visual assessment of staining patterns. Neonates were scored as positive (HbS detected) or negative (no HbS detected) and mothers as AA, AS (sickle trait), or SS (sickle cell disease). Neonatal samples were subsequently tested by isoelectric focusing (IEF) electrophoresis to determine exact sickle cell status. In a cohort of 133 mother-neonate pairs, we used rapid testing on maternal samples to categorize neonates as high-risk (mother positive for HbS) or low-risk (mother negative for HbS). The rapid test was highly accurate in identifying neonates who could be excluded from IEF testing, with a negative predictive value of 93% (Figure 1). In a cohort of 95 neonates similarly triaged by rapid testing on neonatal samples, the negative predictive value of the test was 96% (Figure 2). In both cohorts, the one neonate with HbSS disease was successfully triaged into the high-risk group. Maternal screening with the rapid test would have reduced the proportion of neonates requiring confirmatory IEF testing to 19%, while neonatal screening would have reduced this proportion to 26%. These results indicate the potential utility of the rapid diagnostic test as a screening tool prior to more definitive testing. Used in combination with confirmatory IEF, our rapid test could significantly decrease the cost of newborn screening for SCD and increase its clinical utility by permitting more rapid identification of affected infants. Disclosures Piety: Halcyon Biomedical: Patents & Royalties: Mr. Piety is a co-inventor on a utility PCT application, "Paper-based diagnostic test" (PCT/US2012/064856, 11/13/2012), claiming priority benefit of U.S. 61/692,994 (8/24/2012) and U.S. 61/558,009 (11/10/2011). . Shevkoplyas:Halcyon Biomedical: Equity Ownership, Patents & Royalties: Co-inventor on a utility PCT application, "Paper-based diagnostic test" (PCT/US2012/064856, 11/13/2012), claiming priority benefit of U.S. 61/692,994 (8/24/2012) and U.S. 61/558,009 (11/10/2011). Part-owner of Halcyon Biomedical Inc.,.

scholarly journals HemoTypeSC, a low-cost point-of-care testing device for sickle cell disease: Promises and challenges

2019 ◽  
Vol 78 ◽  
pp. 22-28 ◽  
Author(s):  
Obiageli Nnodu ◽  
Hezekiah Isa ◽  
Maxwell Nwegbu ◽  
Chinatu Ohiaeri ◽  
Samuel Adegoke ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Point Of Care ◽  
Low Cost ◽  
Testing Device ◽  
Cell Disease ◽  
Point Of Care Testing

scholarly journals A Portable Impedance Microflow Cytometer for Measuring Cellular Response to Hypoxia

2021 ◽  
Author(s):  
Darryl Dieujuste ◽  
Yuhao Qiang ◽  
Sarah Du
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cellular Response ◽  
Electrical Impedance ◽  
Low Cost ◽  
Equivalent Circuit Model ◽  
Membrane Capacitance ◽  
Cell Disease ◽  
Microflow Cytometer ◽  
Hypoxia Treatment

This paper presents the development and testing of a low-cost (< $60), portable, electrical impedance based microflow cytometer for single cell analysis under controlled oxygen microenvironment. The system is based on an AD5933 impedance analyzer chip, a microfluidic chip, and an Arduino microcontroller operated by a custom Android application. A representative case study on human red blood cells (RBCs) affected by sickle cell disease is conducted to demonstrate the capability of the cytometry system. An equivalent circuit model of a suspended biological cell is used to interpret the electrical impedance of single flowing RBCs. RBCs exhibit decreased mean membrane capacitance by 24% upon hypoxia treatment while the mean cytoplasmic resistance remains consistent. RBCs affected by sickle cell disease exhibit decreased cytoplasmic resistance and increased membrane capacitance upon hypoxia treatment. Strong correlations are identified between the changes in the cells’ subcellular electrical components and the hypoxia-induced cell sickling process. The results reported in this paper suggest that the developed method of testing demonstrates the potential application for low-cost screening technique for sickle cell disease and other diseases in the field and low-resource settings. The developed system and methodology can be extended to analyze cellular response to hypoxia in other cell types.

scholarly journals Using DNA testing for the precise, definite, and low-cost diagnosis of sickle cell disease and other Haemoglobinopathies: findings from Tanzania

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Heavenlight Christopher ◽  
Adam Burns ◽  
Emmanuel Josephat ◽  
Julie Makani ◽  
Anna Schuh ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Point Of Care ◽  
Low Cost ◽  
Dried Blood Spots ◽  
Cell Disease ◽  
Middle Income ◽  
Hb S ◽  
Sequencing Platforms ◽  
Sanger Method

Abstract Background Sickle cell disease (SCD) is an important cause of under-five mortality. Tanzania is the 5th country in the world with the highest births prevalence of SCD individuals. Significant advances in the neonatal diagnosis of SCD using rapid point-of-care testing have been made. However genetic confirmation is still required for positive cases, in uncertain cases, in multiply transfused patients, to resolve compound heterozygosity (Hb S/ β0 Thal or Hb S/ β+ thal) not uncommon in the coastal regions of East Africa and increasingly also for pre-marital counselling and potentially for future curative approaches such as gene therapy. The currently available DNA tests are prohibitively expensive. Here, we describe an easy-to-use, affordable and accurate β-globin sequencing approach that can be easily integrated within existing NBS for SCD and other haemoglobinopathies especially in Low- and Middle-income Countries. Aim To evaluate an affordable DNA technology for the diagnosis of Sickle cell disease and other haemoglobinopathies in a resource-limited setting. Methods Laboratory-based validation study was conducted by Muhimbili University of Health and Allied Sciences and the University of Oxford involving sequencing of the entire β -haemoglobin locus using the Oxford Nanopore MinION platform. A total number of 36 Dried blood spots and whole blood samples were subjected to conventional protein-based methods (isoelectric focusing, HPLC), and/or sequenced by the Sanger method as comparators. Results Sequencing results for SCD using the MinION were 100% concordant with those from the Sanger method. In addition, the long-read DNA sequencing method enabled the resolution of cases with unusual phenotypes which make up 1% of all children in Tanzania. The cost is £11/ sample for consumables, which is cheaper compared to other sequencing platforms. Conclusions This is the first report of a comprehensive single DNA assay as a definitive diagnostic test for SCD and other haemoglobinopathies. The test is fast, precise, accurate and affordable.

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