| Background: Heparin is a commonly prescribed blood anticoagulant for the treatment of thrombosis.Due to its narrow therapeutic window and individual variation in pharmacokinetics and pharmacodynamics,precise drug administration remains a challenge.Especially for children,pregnant women,the elderly and obese people,conventional dosage calculations based on body weight are less accurate.Heparin level monitoring is crucial to ensure drug efficacy and avoid side effects such as hemorrhage,thrombocytopenia,etc.At present,an integrated system that enables real-time,robust,minimal-damage monitoring of heparin level is still lacking for clinical studies.Method: The feasibility of in vivo real-time monitoring of heparin level had been explored using an integrated microdialysis-coupled microfluidic system and fluorogenic substrate.Microdialysis is a novel technique enabling rapid,on-line sampling of extracellular space in living tissue,e.g.cerebrospinal fluid,interstitial fluid.Microfluidic technology plays a significant role in real-time biomolecules analyzing because of its miniaturization,highthroughput,and automation.The performance of microdialysis probe and microfluidic chip had been separately optimized and then integrated.The performance of this integrated system was tested by continuous monitoring of heparin level in rat.Results: The efficient analyzing for heparin in the blood stream had been demonstrated using this microdialysis-microfluidic system.The heparin profile had been recorded for a period of 7hours in rat.The detection range of the device was determined to be 0.1-1.5 IU/ml.The lag time of this system was 40 min.Moreover,the results generated from this method agreed well with those from conventional assay.Conclusion: The present system provides a novel quantitative monitoring method with great precision,good reproducibility and full data coverage of treatment period.In addition,the small footprint of the device enables flexible use in hospital setting. |
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