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      A microfluidic timer for timed valving and pumping in centrifugal microfluidics

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          Abstract

          The microfluidic timer, a new unit operation for timing of valving and pumping in centrifugal microfluidics.

          Abstract

          Accurate timing of microfluidic operations is essential for the automation of complex laboratory workflows, in particular for the supply of sample and reagents. Here we present a new unit operation for timed valving and pumping in centrifugal microfluidics. It is based on temporary storage of pneumatic energy and time delayed sudden release of said energy. The timer is loaded at a relatively higher spinning frequency. The countdown is started by reducing to a relatively lower release frequency, at which the timer is released after a pre-defined delay time. We demonstrate timing for 1) the sequential release of 4 liquids at times of 2.7 s ± 0.2 s, 14.0 s ± 0.5 s, 43.4 s ± 1.0 s and 133.8 s ± 2.3 s, 2) timed valving of typical assay reagents (contact angles 36–78°, viscosities 0.9–5.6 mPa s) and 3) on demand valving of liquids from 4 inlet chambers in any user defined sequence controlled by the spinning protocol. The microfluidic timer is compatible to all wetting properties and viscosities of common assay reagents and does neither require assistive equipment, nor coatings. It can be monolithically integrated into a microfluidic test carrier and is compatible to scalable fabrication technologies such as thermoforming or injection molding.

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          Most cited references31

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

          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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            Centrifugal microfluidics for biomedical applications.

            The centrifugal microfluidic platform has been a focus of academic and industrial research efforts for almost 40 years. Primarily targeting biomedical applications, a range of assays have been adapted on the system; however, the platform has found limited commercial success as a research or clinical tool. Nonetheless, new developments in centrifugal microfluidic technologies have the potential to establish wide-spread utilization of the platform. This paper presents an in-depth review of the centrifugal microfluidic platform, while highlighting recent progress in the field and outlining the potential for future applications. An overview of centrifugal microfluidic technologies is presented, including descriptions of advantages of the platform as a microfluidic handling system and the principles behind centrifugal fluidic manipulation. The paper also discusses a history of significant centrifugal microfluidic platform developments with an explanation of the evolution of the platform as it pertains to academia and industry. Lastly, we review the few centrifugal microfluidic-based sample-to-answer analysis systems shown to date and examine the challenges to be tackled before the centrifugal platform can be more broadly accepted as a new diagnostic platform. In particular, fully integrated, easy to operate, inexpensive and accurate microfluidic tools in the area of in vitro nucleic acid diagnostics are discussed.
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              Lab on a CD.

              In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.
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                Author and article information

                Journal
                LCAHAM
                Lab on a Chip
                Lab Chip
                Royal Society of Chemistry (RSC)
                1473-0197
                1473-0189
                2015
                2015
                : 15
                : 6
                : 1545-1553
                Article
                10.1039/C4LC01269K
                25648105
                f404e3e3-d9de-43ff-8a29-4b8eca2cb483
                © 2015
                History

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