Development of an ion-channel sensor for heparin detection

Gadzekpo, Victor P. Y.; Bühlmann, Philippe; Xiao, Kang; Aoki, Hiroshi; Umezawa, Yoshio

doi:10.1016/s0003-2670(00)00740-6

Cited by 71 publications

(47 citation statements)

References 39 publications

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“…Subsequent efforts aimed at developing an ICS to measure heparin itself (24) ground and in horse serum gave average concentrations of 1.30 and 1.56 µg/mL, respectively. Using a fresh electrode for each horse serum sample, however, yielded an average concentration of 1.21 µg/mL with a standard deviation of 0.026 µg/mL.…”

Section: Recent Trendsmentioning

confidence: 99%

Peer Reviewed: Ion Channel Sensors Based on Artificial Receptors

Umezewa¹,

Aoki²

2004

Anal. Chem.

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Section: Recent Trendsmentioning

confidence: 99%

Peer Reviewed: Ion Channel Sensors Based on Artificial Receptors

Umezewa¹,

Aoki²

2004

Anal. Chem.

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“…Various approaches such as quartz crystal microbalance, surface plasmon resonance, ion-sensitive fieldeffect transistor, and membrane-based ion-selective electrode involve either protamine or synthetic cationic polymers as heparin probes, and they are based on either surface affinity capture or an automated heparin titration (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Such methods have had variable success in fully achieving the required objectives: selectivity, sensitivity, robustness, and reusability.…”

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confidence: 99%

Monitoring of heparin and its low-molecular-weight analogs by silicon field effect

Milović

Behr

Godin

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Heparin is a highly sulfated glycosaminoglycan that is used as an important clinical anticoagulant. Monitoring and control of the heparin level in a patient's blood during and after surgery is essential, but current clinical methods are limited to indirect and off-line assays. We have developed a silicon field-effect sensor for direct detection of heparin by its intrinsic negative charge. The sensor consists of a simple microfabricated electrolyte-insulatorsilicon structure encapsulated within microfluidic channels. As heparin-specific surface probes the clinical heparin antagonist protamine or the physiological partner antithrombin III were used. The dose-response curves in 10% PBS revealed a detection limit of 0.001 units͞ml, which is orders of magnitude lower than clinically relevant concentrations. We also detected heparin-based drugs such as the low-molecular-weight heparin enoxaparin (Lovenox) and the synthetic pentasaccharide heparin analog fondaparinux (Arixtra), which cannot be monitored by the existing near-patient clinical methods. We demonstrated the specificity of the antithrombin III functionalized sensor for the physiologically active pentasaccharide sequence. As a validation, we showed correlation of our measurements to those from a colorimetric assay for heparin-mediated anti-Xa activity. These results demonstrate that silicon field-effect sensors could be used in the clinic for routine monitoring and maintenance of therapeutic levels of heparin and heparin-based drugs and in the laboratory for quantitation of total amount and specific epitopes of heparin and other glycosaminoglycans.heparin sensors ͉ label-free sensing ͉ medical devices ͉ enoxaparin ͉ fondaparinux

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“…ICSs have advantages in detecting highly hydrophilic and multiply charged ions, for example, phosphate, 6,7 protamine, 8 heparin, 9 oligonucleotides, [10][11][12][13][14] and other biomolecules. [15][16][17] We found that ICSs do not require complete dehydration of the analyte ions from the aqueous phase as reported in previous research, 6 which allows the detection of hydrophilic ions more easily.…”

Section: Introductionmentioning

confidence: 99%

Ion-channel Sensors Based on ETH 1001 Ionophore Embedded in Charged-alkanethiol Self-assembled Monolayers on Gold Electrode Surfaces

et al. 2006

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An ion-channel sensor was demonstrated by immobilizing ETH 1001, an ionophore for ion-selective electrodes, on a gold electrode surface. The approach for preparing the sensor was to incorporate the ionophore into a mixed self-assembled monolayer of 10-mercaptodecanesulfonate and 11-hydroxy-1-undecanethiol formed on the surface. The voltammetric responses for the thus prepared sensor to the primary cation Ca 2+ were observed by using [Fe(CN)6] 3-/4-as an electroactive marker. The ionophore was stably immobilized on the electrode surface with the hydrophobic interaction between its alkyl chains and those of the alkanethiol. The introduction of a proper charge density to the electrode surface improved the sensor sensitivity with retaining the selective response to Ca 2+ against Mg 2+ with concentrations above 10 -4 M.

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Development of an ion-channel sensor for heparin detection

Cited by 71 publications

References 39 publications

Peer Reviewed: Ion Channel Sensors Based on Artificial Receptors

Peer Reviewed: Ion Channel Sensors Based on Artificial Receptors

Monitoring of heparin and its low-molecular-weight analogs by silicon field effect

Ion-channel Sensors Based on ETH 1001 Ionophore Embedded in Charged-alkanethiol Self-assembled Monolayers on Gold Electrode Surfaces

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