This Account summarizes techniques for fabrication and applications in biomedicine of microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The methods and applications described focus on the exploitation of the physical and chemical properties of PDMS in the fabrication or actuation of the devices. Fabrication of channels in PDMS is simple, and it can be used to incorporate other materials and structures through encapsulation or sealing (both reversible and irreversible).

Poly(dimethylsiloxane) as a material for fabricating microfluidic devices.

■ Abstract Fluid flow at the microscale exhibits unique phenomena that can be leveraged to fabricate devices and components capable of performing functions useful for biological studies. The physics of importance to microfluidics are reviewed. Common methods of fabricating microfluidic devices and systems are described. Components, including valves, mixers, and pumps, capable of controlling fluid flow by utilizing the physics of the microscale are presented. Techniques for sensing flow characteristics are described and examples of devices and systems that perform bioanalysis are presented. The focus of this review is microscale phenomena and the use of the physics of the scale to create devices and systems that provide functionality useful to the life sciences.

https://www.researchgate.net/profile/Glennys_Mensing/publication/11260597_Physics_and_applications_of_microfluidics_in_biology/links/5437f5160cf2027cbb206767.pdf

Physics and applications of microfluidics in biology.

Miniaturization can expand the capability of existing bioassays, separation technologies and chemical synthesis techniques. Although a reduction in size to the micrometre scale will usually not change the nature of molecular reactions, laws of scale for surface per volume, molecular diffusion and heat transport enable dramatic increases in throughput. Besides the many microwell-plate- or bead-based methods, microfluidic chips have been widely used to provide small volumes and fluid connections and could eventually outperform conventionally used robotic fluid handling. Moreover, completely novel applications without a macroscopic equivalent have recently been developed. This article reviews current and future applications of microfluidics and highlights the potential of 'lab-on-a-chip' technology for drug discovery.

Lab-on-a-chip: microfluidics in drug discovery.

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

Droplet microfluidics generates and manipulates discrete droplets through immiscible multiphase flows inside microchannels Due to its remarkable advantages, droplet microfluidics bears significant value in an extremely wide range of area In this review, we provide a comprehensive and in-depth insight into droplet microfluidics, covering fundamental research from microfluidic chip fabrication and droplet generation to the applications of droplets in bio(chemical) analysis and materials generation The purpose of this review is to convey the fundamentals of droplet microfluidics, a critical analysis on its current status and challenges, and opinions on its future development We believe this review will promote communications among biology, chemistry, physics, and materials science

Emerging Droplet Microfluidics

A universal microfluidic platform as a multisensor device for cancer diagnostics, developed within the framework of the
EU project SmartHEALTH [1], will be presented. Based on a standardization concept, a microfluidic platform was
realized that contains various functional modules in order to allow in its final setup to run a complete diagnostic assay on
a chip starting with sample preparation to a final detection via a sensor array. A twofold concept was pursued for the
development and standardization: On the one hand, a standard footprint with defined areas for special functional
elements was chosen, on the other hand a toolbox-approach [2] was used whereas in a first instance different functional
fluidic modules were realized, evaluated and afterwards integrated into the microfluidic multisensor platform. One main
characteristic of the platform is that different kind of sensors can be used with the same fluidic chip. For the read-out and
fluidic control of the chip, common fluidic interfaces to the instrument were defined. This microfluidic consumable is a
hybrid system consisting of a polymer component with an integrated sensor, reagent storage on chip, integrated valves
and metering elements.

SmartHEALTH: a microfluidic multisensor platform for POC cancer diagnostics

In this report a fast and robust chip-based capillary electrophoresis (CE) method is described, determining lithium ions in blood samples. The blood plasma was generated with a separate on-chip plasma filtration module. In preceding experiments with the CE system, the detection limit of lithium analyzed on its own was shown to be 50 μmol∙L -1 . Due to the challenging sample matrix, a lithium calibration directly within the blood plasma was performed. A clear separation of lithium and sodium ions could be carried out with a MES/His background electrolyte at a separation voltage of 3.8 kV. The limit of detection for lithium in blood plasma was verified to be less than 250 μmol∙L -1 , assuring a reliable quantification. Combined with the on-chip plasma generation, the time from withdrawing the blood sample to the analysis result was reduced to less than 5 minutes.

Microfluidic device for fast on-site biomedical diagnostic on the example of lithium analysis in blood

For many problems in system biology or pharmacology, in-vivo-like models of cell-cell interactions or organ functions
are highly sought after. Conventional stationary cell culture in 2D plates quickly reaches its limitations with respect to an
in-vivo like expression and function of individual cell types. Microfabrication technologies and microfluidics offer an
attractive solution to these problems. The ability to generate flow as well as geometrical conditions for cell culture and
manipulation close to the in-vivo situation allows for an improved design of experiments and the modeling of organ-like
functionalities. Furthermore, reduced internal volumes lead to a reduction in reagent volumes necessary as well as an
increased assay sensitivity. In this paper we present a range of microfluidic devices designed for the co-culturing of a
variety of cells. The influence of substrate materials and surface chemistry on the cell morphology and viability for long-term
cell culture has been investigated as well as strategies and medium supply for on-chip cell cultivation.

Microfluidic devices for cell culture and handling in organ-on-a-chip applications

Publisher Summary This chapter describes different techniques developed for the fabrication of polymer-based μ -TAS devices using replication methods. Polymer replication methods have gained high attention as alternative fabrication methods for microfluidic devices. They represent a pathway to a commercial fabrication of such devices as well as, in the case of casting and embossing, an attractive way of rapid prototyping. One basic property common for all replication techniques is the need for a replication master. The replication master can be fabricated by a large variety of techniques, covering the whole spectrum of microfabrication technologies developed over the years. The most widely used elastomer used for microfluidic applications is polydimethylsiloxane. Normally, at the end of any of replication processes, a polymer part is not in its final state of its use. To have a device usable for microfluidics, several back-end processes typically have to take place to finish the part. These include enclosing, metallization, and surface modification. The range of polymer materials examined for microfluidic applications is steadily increasing. So it is clear that there is not only the replication method, but for each application, a suitable method should be there to fulfill the user's needs.

Microreplication technologies for polymer-based μ-TAS applications

Cell-based assays and organ-like substrates gather increasing attention due to their potentials in diagnostic and drug development. The use of these cell-based systems will allow to better understand in-vivo processes and to test for the direct influence of different substances on cell viability or metabolic activity e.g. in drug development and in addition to identify the influence of generated metabolites or different cell types. In this paper we present a respective technical platform, which enables the use of such cell-based assays. The platform is based on a microfluidic cell-assay toolbox, designed in a fashion allowing to minimize manual steps for cell culture on chip. Elements being essential for this work include membrane elements integrated into a microfluidic device for the separation of liquid stream together with a targeted supply of reagents and a three dimensional feeding of embedded cells. The influence of the metabolism from one cell type on the other can be evaluated due to the arrangement of cell compartments as interacting networks. A respective Lab-on-a-chip handling platform allows for the direct manipulation on a microscope stage and an incubator-free cell culture. Furthermore, luminescent sensors represent promising tools to be embedded into the microfluidic system to monitor the on-chip conditions or to provide information on cell viability and metabolic activity. Finally, examples for implemented assays on chip will be presented, ranging from cell culture showing the cell behavior in respect to surface functionalization and different growth conditions to finally embedding organ-on-chip structures of cultured cell lines.

Claudia Gärtner

Papers

SmartHEALTH: a microfluidic multisensor platform for POC cancer diagnostics

Microfluidic device for fast on-site biomedical diagnostic on the example of lithium analysis in blood

Microfluidic devices for cell culture and handling in organ-on-a-chip applications

Microreplication technologies for polymer-based μ-TAS applications

Sensor enhanced microfluidic devices for cell based assays and organs on chip