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).

/pdf/microfluidic-lab-on-a-chip-platforms-requirements-3q5qdadspt.pdf

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.

/pdf/microfluidic-platforms-for-lab-on-a-chip-applications-2xenxmlmto.pdf

Microfluidic platforms for lab-on-a-chip applications

Micro total analysis systems. Latest advancements and trends.

Polymers have assumed the leading role as substrate materials for microfluidic devices in recent years. They offer a broad range of material parameters as well as material and surface chemical properties which enable microscopic design features that cannot be realised by any other class of materials. A similar range of fabrication technologies exist to generate microfluidic devices from these materials. This review will introduce the currently relevant microfabrication technologies such as replication methods like hot embossing, injection molding, microthermoforming and casting as well as photodefining methods like lithography and laser ablation for microfluidic systems and discuss academic and industrial considerations for their use. A section on back-end processing completes the overview.

Polymer microfabrication technologies for microfluidic systems

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.

http://www.thesiegrists.com/Jons_Personal_Web_Site/Full_Papers_files/Lab%20on%20a%20Chip%202010%20Gorkin.pdf

Centrifugal microfluidics for biomedical applications

We present two novel fluidic concepts to drastically accelerate the process of mixing in batch-mode (stopped-flow) on centrifugal microfluidic platforms. The core of our simple and robust setup exhibits a microstructured disk with a round mixing chamber rotating on a macroscopic drive unit. In the first approach, magnetic beads which are prefilled into the mixing chamber are periodically deflected by a set of permanent magnets equidistantly aligned at spatially fixed positions in the lab-frame. Their radial positions alternatingly deviate by a slight positive and negative offset from the mean orbit of the chamber to periodically deflect the beads inbound and outbound during rotation. Advection is induced by the relative motion of the beads with respect to the liquid which results from the magnetic and centrifugal forces, as well as inertia. In a second approach—without magnetic beads—the disk is spun upon periodic changes in the sense of rotation. This way, inertia effects induce stirring of the liquids. As a result, both strategies accelerate mixing from about 7 minutes for mere diffusion to less than five seconds. Combining both effects, an ultimate mixing time of less than one second could be achieved.

Batch-mode mixing on centrifugal microfluidic platforms

We present a novel concept of an implantable active microport based on micro technology that incorporates a high-resolution volumetric dosing unit and a drug reservoir into the space of a conventional subcutaneous port. The controlled release of small drug volumes from such an "active microport" is crucial e.g. for innovative methods in cancer treatment or pain therapy. Our microport system delivers a flow rate in the range of 1-50 µl/min and enables a patient-specific release profile. The core of our device is a peristaltic micropump fabricated in bulk silicon micromechanics. It is driven by two piezoelectric diaphragm actuators and features a backpressure-independent volumetric dosing capability. Due to the small dead volumes of this microfluidic system a simple and economic medical-grade pressure sensor can be used for real-time release control and detection of catheter occlusion.

Design of an implantable active microport system for patient specific drug release

This paper reports on significant progress in the development of an implantable active microport system for an automated administration of aqueous drug suspensions. A novel piezoelectric two-stage micropump ensures the controlled release of minute amounts of fluid with flow rates between 0.1 μl/min and 50 μl/min. A modification of the chamber design reduces the detrimental effect of entrapped air bubbles. The absence of air bubbles in the pump chamber yields a significantly enhanced accuracy of the delivered fluid volumes. An optimized actuation scheme referred to as gas pumping mode is proposed for the transport of gas. For alternate gas and liquid pumping a critical compression ratio is analytically derived which is determined by the capillary pressure drop of a gas–liquid interface trapped in the pump chamber. Due to an increased compression ratio of the new pump chamber design the micropump has now a full capability to pump both gas and liquid which enables a reliable self-priming.

An implantable active microport based on a self-priming high-performance two-stage micropump

In this paper we present the state of the art of our artificial sphincter project. A novel silicon micropump has been designed recently for this system that features a four-membrane actuator set-up. The four-membrane micropump can transport fluid bidirectional with a maximum flow rate of 4.1 ml/min and can build up a back pressure of 60 kPa. The total size of the micropump is 30 mm × 12 mm × 1 mm. The novel pump is modeled by a lumped-parameter approach and compared to our three-membrane design. The main advantage of an additional membrane is a reduction of the driving frequency of the micropump while the flow rate remains the same compared to a three-membrane model. Consequently, the power consumption of the micropump can be reduced. A reliability analysis shows that the four-membrane micropump is more reliable then our previous design. The micropump was integrated into the artificial sphincter prosthesis. The first in vivo experiment is described and the measured data of the prosthesis implanted in a mini pig are given.

A novel artificial sphincter prosthesis driven by a four-membrane silicon micropump ☆

Characterization of active silicon microvalves with piezoelectric membrane actuators

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