Flow injection analysis. New tool for old assays. New approach to analytical measurements

Stewart, Kent K.

doi:10.1021/ac00260a001

Anal. Chem.

1983

DOI: 10.1021/ac00260a001

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Flow injection analysis. New tool for old assays. New approach to analytical measurements

Kent K. Stewart¹

Abstract: Since its conception in the early 1970s flow injection analysis (FIA) has grown enormously. Today many believe that it has the potential to become the method of choice for many automated and semiautomated assays. A number of reviews (1-5), one textbook (6), and two views of its early history (7,8) have appeared. Papers on all aspects of FIA are appearing with increasing frequency in the literature. In this REPORT the standard uses of FIA will be briefly reviewed, and the unique features of FIA as an analytical… Show more

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Cited by 22 publications

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“…Multiphase flow in microfluidics systems can address the problems that arise in single-phase flow. By forming air−liquid segments within capillaries, − segmented flow injection analysis has been used for automated analysis of samples, including blood. , Discrete air bubbles were used to separate aqueous samples within the capillaries.…”

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On-Chip Titration of an Anticoagulant Argatroban and Determination of the Clotting Time within Whole Blood or Plasma Using a Plug-Based Microfluidic System

et al. 2006

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This paper describes extending plug-based microfluidics to handling complex biological fluids such as blood, solving the problem of injecting additional reagents into plugs, and applying this system to measuring of clotting time in small volumes of whole blood and plasma. Plugs are droplets transported through microchannels by fluorocarbon fluids. A plug-based microfluidic system was developed to titrate an anticoagulant (argatroban) into blood samples and to measure the clotting time using the activated partial thromboplastin time (APTT) test. To carry out these experiments, the following techniques were developed for a plug-based system: (i) using Teflon AF coating on the microchannel wall to enable formation of plugs containing blood and transport of the solid fibrin clots within plugs, (ii) using a hydrophilic glass capillary to enable reliable merging of a reagent from an aqueous stream into plugs, (iii) using bright-field microscopy to detect the formation of a fibrin clot within plugs and using fluorescent microscopy to detect the production of thrombin using a fluorogenic substrate, and (iv) titration of argatroban (0-1.5 μg/mL) into plugs and measurement of the resulting APTTs at room temperature (23 °C) and physiological temperature (37 °C). APTT measurements were conducted with normal pooled plasma (platelet-poor plasma) and with donor's blood samples (both whole blood and platelet-rich plasma). APTT values and APTT ratios measured by the plug-based microfluidic device were compared to the results from a clinical laboratory at 37°C. APTT obtained from the on-chip assay were about double those from the clinical laboratory but the APTT ratios from these two methods agreed well with each other. This paper describes the development of a plug-based microfluidic system capable of titrating an anticoagulant drug, argatroban, into human blood samples and measuring the resulting clotting times. A method for injecting reagents into flowing plugs is also described. Determining the correct dose of an anticoagulant drug is important, as too little of the drug will not be effective while too much of the drug can result in uncontrolled bleeding. Argatroban directly inhibits the active site of thrombin, an essential enzyme in the coagulation cascade. 1 This inhibitor is an effective treatment for heparin-induced thrombocytopenia (HIT). 2 Heparin is a common anticoagulant used to treat thromboembolic diseases and to prevent thrombosis * To whom correspondence should be addressed. E-mail: r-ismagilov@uchicago.edu.. † Department of Chemistry and Institute for Biophysical Dynamics. ‡ Department of Radiology. SUPPORTING INFORMATION AVAILABLEAdditional information as noted in the text: a movie of the merging junction with the hydrophilic glass capillary, where CaCl 2 solution is injected into a plug containing whole blood; a movie of a single plug being followed through a microchannel as a fibrin clot formed within the plug; and characterization of the size of the aqueous plug and the carrier fluid spacing between ...

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On-Chip Titration of an Anticoagulant Argatroban and Determination of the Clotting Time within Whole Blood or Plasma Using a Plug-Based Microfluidic System

et al. 2006

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Reaktionen in Mikrofluidiktröpfchen

2006

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Tröpfchenbasierte Mikrofluidiksysteme bieten in der Chemie und Biologie ausgezeichnete experimentelle Möglichkeiten für die Grundlagenforschung und angewandte Forschung. Sie ermöglichen die Miniaturisierung von Reaktionen, indem Reaktionsvolumina in femto‐ bis mikrolitergroßen Tröpfchen kompartimentiert werden. Die Kompartimentierung in Tröpfchen ermöglicht die schnelle Durchmischung der Reagentien, die zeitliche Steuerung der Reaktionen im Bereich von Millisekunden bis zu Monaten, die Steuerung von Grenzflächeneigenschaften und die Synthese und den Transport von festen Reagentien und Produkten. Mithilfe von tröpfchenbasierten Mikrofluidiksystemen können Anwendungen im Bereich des chemischen und biologischen Screenings, der Proteinkristallisation und der Enzymkinetik verbessert und beschleunigt werden. Darüber hinaus bietet die mögliche Steuerung von Tröpfchen in Mikrofluidikeinheiten Aussichten auf neue wissenschaftliche Methoden und Erkenntnisse.

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Reactions in Droplets in Microfluidic Channels

2006

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Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems. These systems enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes. Compartmentalization in droplets provides rapid mixing of reagents, control of the timing of reactions on timescales from milliseconds to months, control of interfacial properties, and the ability to synthesize and transport solid reagents and products. Droplet-based microfluidics can help to enhance and accelerate chemical and biochemical screening, protein crystallization, enzymatic kinetics, and assays. Moreover, the control provided by droplets in microfluidic devices can lead to new scientific methods and insights.

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Flow injection analysis. New tool for old assays. New approach to analytical measurements

Cited by 22 publications

References 40 publications

On-Chip Titration of an Anticoagulant Argatroban and Determination of the Clotting Time within Whole Blood or Plasma Using a Plug-Based Microfluidic System

On-Chip Titration of an Anticoagulant Argatroban and Determination of the Clotting Time within Whole Blood or Plasma Using a Plug-Based Microfluidic System

Reaktionen in Mikrofluidiktröpfchen

Reactions in Droplets in Microfluidic Channels

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