There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

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

Micromachining technology was used to prepare chemical analysis systems on glass chips (1 centimeter by 2 centimeters or larger) that utilize electroosmotic pumping to drive fluid flow and electrophoretic separation to distinguish sample components. Capillaries 1 to 10 centimeters long etched in the glass (cross section, 10 micrometers by 30 micrometers) allow for capillary electrophoresis-based separations of amino acids with up to 75,000 theoretical plates in about 15 seconds, and separations of about 600 plates can be effected within 4 seconds. Sample treatment steps within a manifold of intersecting capillaries were demonstrated for a simple sample dilution process. Manipulation of the applied voltages controlled the directions of fluid flow within the manifold. The principles demonstrated in this study can be used to develop a miniaturized system for sample handling and separation with no moving parts.

Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip

Isothermal amplification of nucleic acids is a simple process that rapidly and efficiently accumulates nucleic acid sequences at constant temperature. Since the early 1990s, various isothermal amplification techniques have been developed as alternatives to polymerase chain reaction (PCR). These isothermal amplification methods have been used for biosensing targets such as DNA, RNA, cells, proteins, small molecules, and ions. The applications of these techniques for in situ or intracellular bioimaging and sequencing have been amply demonstrated. Amplicons produced by isothermal amplification methods have also been utilized to construct versatile nucleic acid nanomaterials for promising applications in biomedicine, bioimaging, and biosensing. The integration of isothermal amplification into microsystems or portable devices improves nucleic acid-based on-site assays and confers high sensitivity. Single-cell and single-molecule analyses have also been implemented based on integrated microfluidic systems. In this review, we provide a comprehensive overview of the isothermal amplification of nucleic acids encompassing work published in the past two decades. First, different isothermal amplification techniques are classified into three types based on reaction kinetics. Then, we summarize the applications of isothermal amplification in bioanalysis, diagnostics, nanotechnology, materials science, and device integration. Finally, several challenges and perspectives in the field are discussed.

Isothermal Amplification of Nucleic Acids

This paper reviews the centrifugal 'Bio-Disk' platform which is based on rotationally controlled, multi-scale liquid handling to fully integrate and automate complex analysis and synthesis protocols in the life sciences. The platform offers the crucial ingredients for a rapid development of applications: a coherent library of fluidic unit operations, a device technology for actuation, liquid interfacing and detection as well as a developer toolbox providing experimental testing, rapid prototyping and simulation capabilities. Various applications in the fields of life science, in vitro diagnostics and micro-process engineering are demonstrated.

https://iopscience.iop.org/article/10.1088/0960-1317/17/7/S07/pdf

The centrifugal microfluidic Bio-Disk platform

https://www.imtek.de/data/lehrstuehle/app/dokumente/publikationen/publpdf2008/kerzenmacher-energy-harvesting-by-implantable.pdf

Energy harvesting by implantable abiotically catalyzed glucose fuel cells

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 centrifugal process for the extraction of plasma from sediment by a decanting structure, terminating with metered plasma which is readily available for subsequent on-disk processing. Our technique supplies 2 ml plasma from 5 ml of whole blood at moderate spinning frequencies of 40 Hz within 20 s, only. The residual cell concentration in the purified plasma amounts to less than 0.11%, independent of the frequency of rotation. A capillary duct connects the extracted plasma to subsequent on-disk processing units.

/pdf/centrifugal-extraction-of-plasma-from-whole-blood-on-a-5c5z7usz7b.pdf

Centrifugal extraction of plasma from whole blood on a rotating disk

We present a novel, cost-efficient process chain for fast tooling and small-lot replication of high-quality, multi-scale microfluidic polymer chips within less than 5 days. The fabrication chain starts with a primary master which is made by well-established cleanroom processes such as DRIE or negative SU-8 resist based surface micromachining. The formation of undercuts in the master which would complicate demolding is carefully avoided. Secondary PDMS masters or epoxy-based masters which are more suitable for common polymer replication schemes such as soft-embossing, hot-embossing or injection molding are subsequently cast from the primary masters. The polymer replica are mainly made of COC and show excellent fidelity with the conventionally micromachined master while displaying no degeneration, even after more than 200 cycles. The use of other polymers such as PMMA is also possible. The process chain further includes surface modification techniques for overall, long-term stable hydrophilic coatings and for local hydrophobic patches as well as a durable sealing based on thermal bonding.

/pdf/rapid-prototyping-of-microfluidic-chips-in-coc-1700k7mije.pdf

Jens Ducrée

Papers

The centrifugal microfluidic Bio-Disk platform

Energy harvesting by implantable abiotically catalyzed glucose fuel cells

Batch-mode mixing on centrifugal microfluidic platforms

Centrifugal extraction of plasma from whole blood on a rotating disk

Rapid prototyping of microfluidic chips in COC