Flow Injection Analysis

This critical review summarizes developments in microfluidic platforms that enable the miniaturization, integration, automation and parallelization of (bio-)chemical assays (see S. Haeberle and R. Zengerle, Lab Chip, 2007, 7, 1094–1110, for an earlier review). In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the easy, fast, and cost-efficient implementation of different application-specific (bio-)chemical processes. In our review we focus on recent developments from the last decade (2000s). We start with a brief introduction into technical advances, major market segments and promising applications. We continue with a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations of every platform. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electrokinetics, electrowetting, surface acoustic waves, and dedicated systems for massively parallel analysis. This review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposability, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols (295 references).

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Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications

We review microfluidic platforms that enable the miniaturization, integration and automation of biochemical assays. Nowadays nearly an unmanageable variety of alternative approaches exists that can do this in principle. Here we focus on those kinds of platforms only that allow performance of a set of microfluidic functions—defined as microfluidic unit operations—which can be easily combined within a well defined and consistent fabrication technology to implement application specific biochemical assays in an easy, flexible and ideally monolithically way. The microfluidic platforms discussed in the following are capillary test strips, also known as lateral flow assays, the “microfluidic large scale integration” approach, centrifugal microfluidics, the electrokinetic platform, pressure driven droplet based microfluidics, electrowetting based microfluidics, SAW driven microfluidics and, last but not least, “free scalable non-contact dispensing”. The microfluidic unit operations discussed within those platforms are fluid transport, metering, mixing, switching, incubation, separation, droplet formation, droplet splitting, nL and pL dispensing, and detection.

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Microfluidic platforms for lab-on-a-chip applications

Introduction A Why POC Diagnostics? B Time B Patient Responsibility and Compliance B Cost B Diagnostic Targets C Proteins C Metabolites and Other Small Molecules C Nucleic Acids C Human Cells D Microbes/Pathogens D Drugs and Food Safety D Current Context of POC Assays E POC Glucose Assays E Lateral Flow Assays E Limitations of “Traditional” POC Approaches F Enabling Technologies G Printing and Laminating G Microfluidic Technologies and Approaches: “Unit Operations” for POC Devices G Pumping and Valving H Mixing I Separation I Reagent Storage J Sample Preparation K Surface Chemistry and Device Substrates L Physical Adsorption L Bioaffinity Attachment L Covalent Attachment M Substrate Materials M Detection M Electrochemical Detection N Optical Detection N Magnetic Detection N Label-Free Methods O Enabling Multiplexed Assays O Recent Innovation O Lateral Flow Assay Technologies O Proteins P Antibodies P Protein Expression and Purification Q Nucleic Acids Q Aptamers R Infectious Diseases and Food/Water Safety R Blood Chemistry S Coagulation Markers S Whole Cells S Trends, Unmet Needs, Perspectives T Glucose T Global Health and the Developing World T Personalized Medicine and Home Testing U Technology Trends U Multiplexing V Author Information V Biographies V Acknowledgment W References W

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Point of care diagnostics: Status and future

This invention provides methods and apparatus for performing microanalytic and microsynthetic analyses and procedures. Specifically, the invention provides a microsystem platform for use with a micromanipulation device to manipulate the platform by rotation, thereby utilizing the centripetal force resulting from rotation of the platform to motivate fluid movement through microchannels embedded in the microplatform. The microsystem platforms of the invention are also provided having microfluidics components, resistive heating elements, temperature sensing elements, mixing structures, capillary and sacrificial valves, and methods for using these microsystems platforms for performing biological, enzymatic, immunological and chemical assays. An electronic spindle designed rotor capable of transferring electrical signals to and from the microsystem platforms of the invention is also provided.

Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system

Design features and operation of a prototype miniaturized Fast Analyzer are described, and some results obtained with it are presented. The Analyzer occupies only one cubic foot of space. It has a 17-cuvet plastic rotor that rotates through a stationary optical system at speeds up to 5000 rpm. The resulting centrifugal force is utilized to transfer and mix a series of sample(s) and reagent(s) into the cuvets. The ensuing reactions are monitored spectrophotometrically, and the data evaluated in real time by an on-line computer. Samples (1 to 10 µl) and reagents (70 to 110 µl) are loaded into the rotor either discretely or dynamically; various rotor configurations can be used to do this. Many of the standard clinical analyses, including most of the NADH-linked enzymatic analyses, have been adapted for use with this analyzer. Precision obtained ranges from 1 to 4%. This report considers, specifically, analyses of some serum enzymes. Results show that the small analyzer possesses the previously demonstrated advantages of Fast Analyzers and, in addition, has several beneficial features arising from miniaturization.

Development of a miniature fast analyzer.

A modified version of a previously described miniature Fast Analyzer [ Clin. Chem. 18, 753 (1972)] was used as the basis for developing a compact, potentially portable, analytical system. This system includes an automated and versatile sample-reagent loader, a miniature Fast Analyzer, several plastic rotors and their cleaning station, and a portable data system. The sample-reagent loader combines a unique turntable assembly and two "Micromedic" pipets to quickly (5 min per rotor), accurately, and precisely obtain, transfer, and dispense small volumes of sample (1 to 10 µl of sample, 50 µl of diluent) and reagent (20 µl of reagent, 50 µl of diluent) into their respective cavities in a 17-cuvet rotor. The loader uses separate sample and reagent carousels, which allows operation of the system in either the single-sample—multiple-chemistry, multiple-sample— single-chemistry, or multiple-sample—multiple-chemistry analytical modes. The miniature Fast Analyzer rotates a loaded 17-cuvet rotor through a stationary optical system at speeds up to 5000 rpm. The resulting centrifugal force is used to mix and to transfer the discrete aliquots of sample(s) and reagent(s) into their respective cuvets. The ensuing reactions are monitored photometrically, and the data are processed in real time by either a portable Data Processor [ Clin Chem. 18, 762 (1972)] or an on-line computer. A major improvement to the analyzer has been the addition of a temperature-control system that allows the temperature of the spinning rotor to be monitored and controlled to within ±0.2°C. After completion of an analytical run, the rotor is automatically washed and dried in the rotor cleaning station. Many of the standard clinical analyses, including most of the NADH-linked enzymatic analyses, have been adapted for use with this system.

Development of an Analytical System Based Around a Miniature Fast Analyzer

A multiple-sample centrifugal rotor for blood fraction preparation is described. The rotor assembly includes an inner disk-shaped portion defining a circular array of whole blood sample-receiving chambers. Blood samples are statically loaded into the respective chambers through static loading ports. Liquids for washing and hemolyzing the cell fractions are introduced to the chambers following recovery of the plasma fraction by means of a central dynamic distribution port and a multiplicity of distribution passageways extending between the dynamic distribution port and the centrifugal ends of respective chambers. Unloading of blood fractions and washing liquid is accomplished through transfer passageways extending from a point intermediate the centrifugal and centripetal ends of the chambers radially inward and then outward to the periphery of the inner disk-shaped rotor assembly portion. A removable outer rotor portion defining at least one collection chamber for receiving materials discharged from the transfer passageways is nested concentrically about the inner rotor assembly portion.

Multiple-sample rotor assembly for blood fraction preparation

Dynamic multicuvette fluorometer-spectrophotometer based on the GeMSAEC fast analyzer principle

A hydrazine oxalate [(N2H5)2C2O4] solution was used as an alternative wash method for cleaning 30% tributyl phosphate–70% normal paraffin hydrocarbon solvent. Experimental evidence shows the (N2H5)...

J. C. Mailen

Papers

Development of a miniature fast analyzer.

Development of an Analytical System Based Around a Miniature Fast Analyzer

Multiple-sample rotor assembly for blood fraction preparation

Dynamic multicuvette fluorometer-spectrophotometer based on the GeMSAEC fast analyzer principle

An Alternative Solvent Cleanup Method Using a Hydrazine Oxalate Wash Reagent