Highly sensitive ratiometric detection of heparin and its oversulfated chondroitin sulfate contaminant by fluorescent peptidyl probe

Mehta, Pramod Kumar; Lee, Hyeri; Lee, Keun‐Hyeung

doi:10.1016/j.bios.2017.01.002

Cited by 35 publications

(22 citation statements)

References 40 publications

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“…Lee et al [ 67 ] synthesized a heparin-induced self-assembly fluorescent peptide probe with an aggregation-induced emission fluorophore, which was able to form nanoscale aggregates binding with heparins in order to measure the amount of heparins. Since OSCS has an inhibitory effect on heparinase, Mehta et al [ 68 ] had developed a method which was able to detect as low as 0.0001% of OSCS contamination in heparins by adding heparinase into the mixture of heparins and detected the fluorescent change. If heparins were contaminated by OSCS, the changes in fluorescence intensity were reduced compared to the uncontaminated standard.…”

Section: Analysis Of Heparinsmentioning

confidence: 99%

Techniques for Detection of Clinical Used Heparins

Zhao

2021

International Journal of Analytical Chemistry

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Heparins and sulfated polysaccharides have been recognized as effective clinical anticoagulants for several decades. Heparins exhibit heterogeneity depending on the sources. Meanwhile, the adverse effect in the clinical uses and the adulteration of oversulfated chondroitin sulfate (OSCS) in heparins develop additional attention to analyze the purity of heparins. This review starts with the description of the classification, anticoagulant mechanism, clinical application of heparins and focuses on the existing methods of heparin analysis and detection including traditional detection methods, as well as new methods using fluorescence or gold nanomaterials as probes. The in-depth understanding of these techniques for the analysis of heparins will lay a foundation for the further development of novel methods for the detection of heparins.

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Section: Analysis Of Heparinsmentioning

confidence: 99%

Techniques for Detection of Clinical Used Heparins

Zhao

2021

International Journal of Analytical Chemistry

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“…Other recently reported dye-based heparin assays are more selective but have not yet been studied in complex biological samples (Bromfield et al 2013;Buee et al 1991). Colorimetric assays for heparin are either limited to plasma or buffer or have not yet been demonstrated in whole blood (Mehta et al 2017;Templeton 1988;You et al 2017). The aPTT is limited by its range of detection, variation in reagents, and instrumentation (Baglin et al 2006;Lehman and Frank 2009).…”

Section: Heparin Sensing In Banked Clinical Plasma Specimensmentioning

confidence: 99%

“…Direct detection of heparin under biologically relevant conditions could be useful in monitoring heparin-based therapy. Other approaches utilize micro-electromechanical film bulk acoustic sensors (Chen et al 2017a;Chen et al 2017b), nanoparticles (Ma et al 2014), cationic fluorescent/phosphorescent polymers (Ma et al 2014;Mehta et al 2017;Pu and Liu 2009;Shi et al 2016), and small molecule sensors via aggregation-induced emission (Zheng et al 2017). Mallard blue dye and gold nanoparticles capable of selectively sensing heparin and other sulfated glycosaminoglycans were also recently described in detail (Bromfield et al 2013;Kalita et al 2014;Shriver and Sasisekharan 2013).…”

Section: Introductionmentioning

confidence: 99%

A cellulose-based photoacoustic sensor to measure heparin concentration and activity in human blood samples

Jeevarathinam

Pai

Huang

et al. 2019

Biosensors and Bioelectronics

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Heparin is an indispensable drug in anticoagulation therapy but with a narrow therapeutic window, which dictates regular testing and dose adjustment. However, current monitoring tools have a long turnaround time or are operator intensive. In this work, we describe a cellulose-based photoacoustic sensor for heparin. The sensors have a turnaround time of 6 minutes for whole blood samples and 3 minutes for plasma samples regardless of heparin concentration. These sensors have a limit of detection of 0.28 U/ml heparin in human plasma and 0.29 U/ml in whole blood with a linear response (Pearson's r = 0.99) from 0 -2 U/ml heparin in plasma and blood samples. The relative standard deviation was <12.5% in plasma and < 17.5% in whole blood. This approach was validated with heparin-spiked whole human blood and had a linear correlation with the activated partial thromboplastin time (aPTT) (r = 0.99). We then studied 16 sets of clinical samples-these had a linear correlation with the activated clotting time (ACT) (Pearson's r = 0.86, P<0.0001). The photoacoustic signal was also validated against the cumulative heparin dose (Pearson's r = 0.80, P<0.0001). This approach could have applications in bed-side heparin assays for continuous heparin monitoring.

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“…61 By adding a heparinase, the digestive activity of which is selectively inhibited by OCSC, into solutions of contaminated UFH and a pyrene-appended peptide, Lee et al were able to detect as low as 0.0001% (w/w) OSCS contamination by monitoring the decrease of fluorescent change due to undigested heparin. 62 However, the optical response to GAGs was dependent on the concentration of these previous chemosensors since GAGs mainly consist of disaccharide repeating units. This drawback was circumvented by linking two pyrene labeled heparin-binding peptides using a glycine-rich (i.e., hydrophobic) spacer.…”

Section: ■ Heparin Monitoringmentioning

confidence: 99%

“…61 The U.S. FDA currently recommends highly sophisticated and expensive orthogonal methods such as high performance liquid chromatography combined with nuclear magnetic and mass spectroscopy to detect and identify contaminants in UFH. 129 In order to provide less costly and easier to implement quality controls, some of the sensors have been upgraded toward (i) the detection of very low concentrations of OSCS contaminants by exploiting the selective degradation of UFH by the heparinase enzyme 62,65,75 or (ii) the differentiation of mixtures of GAGs by using an array of sensors. 100 Finally, the implementability of the reported sensors at the point-of-care has yet to be demonstrated.…”

Section: ■ Heparin Monitoringmentioning

confidence: 99%

Lost in (Clinical) Translation: Recent Advances in Heparin Neutralization and Monitoring

Ourri

Vial

2019

ACS Chem. Biol.

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The heparin family, which includes unfractionated heparin, low-molecular heparin and fondaparinux, is a class of drugs clinically used as intravenous blood thinner. To date, issues related to both to the reversal of anticoagulation and the blood level determination of the anticoagulant at the point-of-care remain: while the only U.S. Food and Drug Administration (FDA) approved antidote for heparin displays serious efficacy and safety drawbacks, the current assays for heparin monitoring are indirect measurements subject to their own limitations and variations. Herein, we provide an update on the numerous recent chemical approaches to tackle these issues, from which it is clear that some new antidotes and sensors for heparin certainly have the potential to exceed current clinical standards. This review aims to review a field that requires close collaborations between physicians, biologists and chemists in order to foster advances toward clinical translation. Context and challengesHeparin, which belongs to the family of glycosaminoglycans (GAGs), is a linear sulfated polysaccharide and consists of repeating disaccharide subunits of α-1,4 linked uronic acid and D-glucosamine (Figure 1). As a consequence, heparin displays the highest density of negative charges among biomacromolecules. This polyanion is widely used as an intravenous anticoagulant due to its ability to accelerate the rate at which antithrombin (AT) inhibits serine proteases within the blood coagulation cascade, most notably factor Xa and thrombin. [1][2][3][4] Polymers of various lengths such as unfractionated heparin (UFH, Mw ~ 15 kDa), low-molecular-weight heparins (LMWHs, Mw = 3.6-6.5 kDa), and the synthetic pentasaccharide fondaparinux (Mw = 1.7 kDa) are routinely delivered to patients. While UFH is used during acute thrombotic events or to maintain blood fluidity during procedures requiring extracorporeal circulation (i.e., cardio-pulmonary bypass or hemodialysis), 5,6 LMWHs and fondaparinux are prescribed to treat and/or prevent deep vein thrombosis and pulmonary embolism. 7,8 With an estimated one billion doses of heparin produced every year, heparin's market is rapidly growing, driven by the ageing of populations and the increasing incidence of cardiovascular diseases. 9 KeywordsAnticoagulants: commonly known as blood thinners, they are chemical substances that retard or inhibit the coagulation of the blood.

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Highly sensitive ratiometric detection of heparin and its oversulfated chondroitin sulfate contaminant by fluorescent peptidyl probe

Cited by 35 publications

References 40 publications

Techniques for Detection of Clinical Used Heparins

Techniques for Detection of Clinical Used Heparins

A cellulose-based photoacoustic sensor to measure heparin concentration and activity in human blood samples

Lost in (Clinical) Translation: Recent Advances in Heparin Neutralization and Monitoring

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