▪ Abstract Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in bas-relief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (≥50 μm), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.

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Soft Lithography in Biology and Biochemistry

We survey progress over the past 25 years in the development of microscale devices for pumping fluids. We attempt to provide both a reference for micropump researchers and a resource for those outside the field who wish to identify the best micropump for a particular application. Reciprocating displacement micropumps have been the subject of extensive research in both academia and the private sector and have been produced with a wide range of actuators, valve configurations and materials. Aperiodic displacement micropumps based on mechanisms such as localized phase change have been shown to be suitable for specialized applications. Electroosmotic micropumps exhibit favorable scaling and are promising for a variety of applications requiring high flow rates and pressures. Dynamic micropumps based on electrohydrodynamic and magnetohydrodynamic effects have also been developed. Much progress has been made, but with micropumps suitable for important applications still not available, this remains a fertile area for future research.

https://microfluidics.stanford.edu/Publications/Micropumps_Cooling/Laser%20Review%20of%20Micropumps%20in%20JMM.pdf

A review of micropumps

■ 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.

This review reports the progress on the recent development of micromixers. The review first presents the different micromixer types and designs. Micromixers in this review are categorized as passive micromixers and active micromixers. Due to the simple fabrication technology and the easy implementation in a complex microfluidic system, passive micromixers will be the focus of this review. Next, the review discusses the operation points of the micromixers based on characteristic dimensionless numbers such as Reynolds number Re, Peclet number Pe, and in dynamic cases the Strouhal number St. The fabrication technologies for different mixer types are also analysed. Quantification techniques for evaluation of the performance of micromixers are discussed. Finally, the review addresses typical applications of micromixers.

https://iopscience.iop.org/article/10.1088/0960-1317/15/2/R01/pdf

Micromixers?a review

This thesis explores transport phenomena in nanochannels on a chip. Fundamental nanofluidic ionic studies form the basis for novel separation and preconcentration applications for proteomic purposes. The measurements were performed with 50-nm-high 1D nanochannels, which are easily accessible from both sides by two microchannels. Nanometer characteristic apertures were manufactured in the bonded structure of Pyrex-amorphous silicon – Pyrex, in which the thickness of the amorphous silicon layer serves as a spacer to define the height of the nanochannels. The geometry of the nanometer-sized apertures is well defined, which simplifies the modeling of the transport across them. Compared to biological pores, the present nanochannels in Pyrex offer increased stability. Fundamental characteristics of nanometer-sized apertures were obtained by impedance spectroscopy measurements of the nanochannel at different ionic strengths and pH values. A conductance plateau (on a log-log scale) was modeled and measured, establishing due to the dominance of the surface charge density in the nanochannels, which induces an excess of mobile counterions to maintain electroneutrality. The nanochannel conductance can be regulated at low ionic strengths by pH adjustment, and by an external voltage applied on the chip to change the zeta potential. This field-effect allows the regulation of ionic flow which can be exploited for the fabrication of nanofluidic devices. Fluorescence measurements confirm that 50-nm-high nanochannels show an exclusion of co-ions and an enrichment of counterions at low ionic strengths. This permselectivity is related to the increasing thickness of the electrical double layer (EDL) with decreasing salt concentrations, which results in an EDL overlap in an aperture if the height of the nanochannel and the thickness of the EDL are comparable in size. The diffusive transport of charged species and therefore the exclusion-enrichment effect was described with a simple model based on the Poisson-Boltzmann equation. The negatively charged Pyrex surface of the nanometer characteristic apertures can be inversed with chemical surface pretreatments, resulting in an exclusion of cations and an enrichment of anions. When a pressure gradient is applied across the nanochannels, charged molecules are electrostatically rejected at the entrance of the nanometer-sized apertures, which can be used for separation processes. Proteomic applications are presented such as the separation and preconcentration of proteins. The diffusion of Lectin proteins with different isoelectric points and very similar compositions were controlled by regulating the pH value of the buffer. When the proteins are neutral at their pI value, the diffusion coefficient is maximal because the biomolecules does not interact electrostatically with the charged surfaces of the nanochannel. This led to a fast separation of three Lectin proteins across the nanochannel. The pI values measured in this experiment are slightly shifted compared to the values obtained with isoelectric focusing because of reversible adsorption of proteins on the walls which affects the pH value in the nanochannel. An important application in the proteomic field is the preconcentration of biomolecules. By applying an electric field across the nanochannel, anionic and cationic analytes were preconcentrated on the cathodic side of the nanometer-sized aperture whereas on the anodic side depletion of ions was observed. This is due to concentration polarization, a complex of effects related to the formation of ionic concentration gradients in the electrolyte solution adjacent to an ion-selective interface. It was measured that the preconcentration factor increased with the net charge of the molecule, leading to a preconcentration factor of > 600 for rGFP proteins in 9 minutes. Such preconcentrations are important in micro total analysis systems to achieve increased detection signals of analytes contained in dilute solutions. Compared to cylindrical pores, our fabrication process allows the realization of nanochannels on a chip in which the exclusion-enrichment effect and a big flux across the nanometer-sized aperture can be achieved, showing the interest for possible micro total analysis system applications. The described exclusion-enrichment effect as well as concentration polarization play an important role in transport phenomena in nanofluidics. The appendix includes preliminary investigations in DNA molecule separation and fluorescence correlation spectroscopy measurements, which allows investigating the behavior of molecules in the nanochannel itself.

/pdf/transport-phenomena-in-nanofluidics-1di3nwdyom.pdf

Transport phenomena in nanofluidics

A new silicon-based micropump is described in this paper. The key element of the device is a thick-film/silicon micromachined hybrid actuator. The actuation principle relies on the flexure of a screen printed piezoelectric lead zirconate titanate (PZT) layer on a silicon membrane (8 mm × 4 mm × 70 μm). An investigation into the deposition technology of the bottom electrode for the piezoelectric material showed that a gold resinate or Pt evaporated electrode on a 500 nm thick SiO 2 covered silicon wafer achieved best results for the membrane actuator. Inlet and outlet valves are of the cantilever type and use deep boron diffusion together with KOH etching. Pump rates of up to 120 μl min −1 have been achieved. A maximum backpressure of 2 kPa was measured when using a 600 V pp sinusoidal drive voltage at 200 Hz across a 100 μm thick PZT layer. The pump was compared with a conventional surface mounted piezoelectric driven micropump. The conventional pump achieves a performance which was a factor of 3–6 more efficient, but does not allow mass production.

/pdf/a-novel-micromachined-pump-based-on-thick-film-piezoelectric-13hbsu9lwq.pdf

A novel micromachined pump based on thick-film piezoelectric actuation

This paper reports modelling, fabrication and testing of two micromixers. The principle of mixing used for the devices was diffusion because of the small value of the Reynolds number in microcapillaries. The first mixer separates the main flow into partial flows, which are laterally alternated in order to increase the boundary surface between the liquids. The second mixer superposes two fluids by injection of one liquid into the other. The fabrication technology is based on etching of silicon and anodically bonding with Pyrex glass. The performance of the mixers has been verified by mixing phenolphthalein solution and ammonia dissolved in water. Reasonable mixing was achieved at pressures of around 4 kPa (lateral mixing) and 7 kPa (vertical mixing) with flow rates of approximately 1 . The measurements were compared with diffusive mixing simulations with a CFD simulator and agreement of both was observed.

https://iopscience.iop.org/article/10.1088/0960-1317/8/2/020/pdf

Two simple micromixers based on silicon

This paper reports the design and fabrication of a micromachined Coulter counter. Calculations have been performed to estimate the behaviour of the counter for passing particles. A relative resistance change of 1.8% has been derived for a particle of 1.5 µm radius flowing through a capillary of 5 µm side length and an electrode spacing of 40 µm. The fabrication technology has been based on similar micromachining steps to a micromixer, and allows further design modification to generate other microfluidic devices. Thus, integration of other microfluidic devices is possible with this technology. The fabrication relies on silicon trench etching and subsequent deposition of metal electrodes over the trench edges. Finally, a Pyrex wafer is anodically bonded on top of the silicon to seal the capillaries.

https://iopscience.iop.org/article/10.1088/0960-1317/9/2/313/pdf

Design and fabrication of a micromachined Coulter counter

A hybrid actuated silicon-based micropump with dynamic passive valves is described in this paper. The actuator is based on a combination of thick-film and silicon micromachining technology and relies on the flexure of a membrane structure of lead zirconate titanate on silicon. Inlet and outlet valves use the passive dynamic principle, where flow direction is realized with a diffuser and a nozzle shaped element. Pump rates of up to 155 and a maximum backpressure of 1 kPa were achieved at a driving voltage of 600 . Additionally the fluidic modelling of the dynamic passive valves is described, using a CFD simulator. The results of the model agree well with device measurements.

https://iopscience.iop.org/article/10.1088/0960-1317/8/2/019/pdf

M Koch

Papers

A novel micromachined pump based on thick-film piezoelectric actuation

Two simple micromixers based on silicon

Design and fabrication of a micromachined Coulter counter

The dynamic micropump driven with a screen printed PZT actuator

Microfluidic Technology and Applications