Electrospun fibers for micro-devices

There is a trend for diagnostic and analytic devices to be miniaturized for use at home or to expand its function within a given space and this is where electrospun nanofibers may facilitate. Electrospinning is able to deposit thin layer of nanofibers on various substrates including chips. The nanofibers can be electrospun using various materials and modified to give specific function and its high surface area makes it highly sensitive to the environment. Electrospun fibers membrane also demonstrated properties such as thermal and acoustic insulation. The combination of high surface area and small volume makes electrospun fibers ideal for integration onto miniature devices.

In its nonwoven form, electrospun membrane has been used in air and water filtration. Such filtration system is typically based on size exclusion. Lee et al (2007) explored this property of electrospun membrane for use in hemodialysis device. The electrospun membrane is used to filter out metabolic waste such as urea and creatinine from the blood without changing other metabolic conditions. Electrospun polyethersulfone (PES) and polyurethane (PU) was able to remove urea as effectively as commercially available membranes and the removal of creatinine was better than commercially available membranes with PU nanofiber membrane better than PES nanofiber membrane. The electrospun membrane has no detrimental impact on the red blood cell and the concentration of the electrolytes before and after the chip-based dialysis remains relatively unchanged.

Electrospun fibers on chip allow real time monitoring of cell response to the environment. Liu et al (2016) was able to create hepatocyte spheroid formation on integrated poly-DL-lactide (PLA) patterned electrospun fibers with a polydimethylsiloxane (PDMS) microfluidic chip. With a dynamic culture system, there was hepatocyte polarity which supported biliary excretion and maintained high levels of albumin and urea secretion over 15 days. A flow rate of 10 µL/min was found to be optimum in maintaining hepatocyte viability and significantly stronger biliary excretory function. At this parameters, they found that hepatocyte was most sensitive to 120 µg/ml Ag nanoparticles with 50% cell mortality after 24 hrs exposure to the nanoparticles. Cells cultured to day 7 and day 15 also showed similar mortality after 24 hrs exposure. The same setup has also been used for metabolism tests on tolbutamide and testosterone by hepatocytes [Liu et al 2017].

Electrospun membrane may be modified for selective adsorption of molecules or as enzyme carriers. Jo et al (2011) constructed highly mesoporous nitrilotriacetic acid-functionalized polystyrene (PS-NTA) fibers for immobilizing target proteins from a heterogeneous protein mixture in a microfluidic chip-based device. Liu et al (2009) showed that high surface area of electrospun polyvinylidene fluoride (PVDF) (fiber diameter 600 nm) was able to adsorb eight times more proteins compared to track-etched polycarbonate (TEPC) membranes in a microfluidic chip assembled by polydimethylsiloxane (PDMS). Electrospun nanofibers are a good carrier for quick release of enzyme for applications such as microfluidic detection chip. High surface area of the nanofibers allows rapid dissolution in appropriate water or solvents. Dai et al (2012) used water soluble electrospun polyvinyl pyrrolidone nanofibers as carrier for horseradish peroxidises (HRP). Placed in a microfluidic chip, PVP nanofibers loaded with HRP readily dissolve to release HRP when the aqueous sample passed through it.

While high surface area of electrospun nanofibers have made them useful as an analytical component in the micro-devices, there are other properties of the membrane that makes it useful as a setup component. Electrospun membrane has been shown to exhibit thermal insulation property. As the membrane occupies a small volume and high porosity, it may be used for controlling heat flow into a microfluidic chamber. Jiang et al (2012) used electrospun polyethylene oxide (PEO) as thermal insulating membrane to regulate seed growth in microfluidic chips. Their study showed that the increment of thermal insulating property of the membrane reduces as the electrospinning deposition time increases. With increasing electrospun fiber thickness, the pore size reduces [Jiang et al 2012]. This will contribute to smaller air pockets and reducing insulation performance. In the setup by Jiang et al (2012), thermal radiation is the main heat transfer mechanism. They hypothesized that the insulation property of electrospun membrane comes from the scattering of the electromagnetic waves.

For microfluidic devices, mixing of two or more fluids within the chamber is a challenge given the small chamber size and limited fluid injection. While there are passive micromixers built into microfluidic devices, Matlock-Colangelo et al (2016) proposed electrospun nonwoven nanofibrous membrane as an alternative. They hypothesized that the tortuous path needed by the fluid to navigate through the interconnected network of nanofibers will encourage greater mixing between two injected fluids. In their experiment using electrospun polyvinyl alcohol (PVA) fibers and polystyrene fibers (PS), the PVA nanofibers (450 - 550 nm diameter) membrane was able to produce up to 71% mixing while the PS microfibers (0.8 - 2.7 µm diameter) produced 51% mixing. Without the fibrous membrane, mixing of two fluids were only 29%. While the hydrophobicity of the electrospun membrane may play a part in the mixing (PS much more hydrophobic than PVA), PVA showed that with smaller nanofiber diameter, mixing increases. However, for PS, mixing increases with increasing fiber diameter within the diameter range tested.

Y-channel mixer with embedded nanofiber mats [Matlock-Colangelo et al 2016].

Qiu et al (2022) explored the use of electrospun nanofibers as supporting structures in an integrated 3D microfluidic chip. Using a concept named self-consistent additive manufacturing (NSCAM), electrospinning and electrohydrodynamic jet (E-jet) writing are alternately used to create a composite structure with 3D channels. The interconnected electrospun fibers functioned both as support for the wall material and the percolating media for liquid flow. Therefore, the electrospun fibers actually penetrate through the channels between the walls and its highly porous nature allows liquid to flow through it while providing the necessary support to prevent channel collapse when there is no liquid in them. Polyimide was the material used by Qiu et al (2022) for electrospinning into supporting fibers. E-jet writing of polydimethylsiloxane (PDMS) was performed on alternate layers of electrospun polyimide. A PDMS solution printed on the electrospun porous layers would penetrate into it and by adjusting the temperature, the depth of penetration can be controlled. By controlling the penetration depth of PDMS on alternate layers of electrospun fibers, channels can be created in a 3D space with a horizontal resolution of 120 µm and vertical resolution of 45 µm. Qiu et al (2022) was able to construct a microfluidic pressure-gain valve using this concept.

NSCAM procedures for 3D microfluidic devices. (a) 3D microfluidic channels fabricated by alternate electrospinning and E-jet writing. (b) The NSCAM process for a 3D microfluidic pressure-gain valve. i: electrospinning; ii: the E-jet ink is written on the nanofiber substrate and then permeates the porous membrane; iii, iv: the construction of the control channel layer by patterned CF penetration; v, vi: sealing the channel by controlling the CF vertical penetration distance; vii-xiv: the construction of the input channel layer, connecting layer, output channel and channel cover layer; xv-xvi: the principle of the 3D microfluidic pressure-gain valve [Qiu et al 2022].

An advantage of electrospinning in the production of nanofibers is the ability to create ordered fiber alignment. Aligned nanofibers made of appropriate material have the potential to exhibit polarised light emission. The small area and volume it occupies make it possible for integration into microfluidic devices. Pagliara et al (2009) electrospun aligned light-emitting conjugated polymer poly[2-methoxy,5-(2- ethylhexyloxy)-phenylene-vinylene] (MEH-PPV)/poly(methylmethacrylate) (PMMA) by using parallel electrodes collector setup. A laser source shining on the nanofibers causes the embedded fluorophores to absorb and re-emit light isotropically. This polarised light-emitting array can be used to excite flowing dye chromophores in microchannels with a significant increase of imaging signal/excitation background (S/N) ratio with respect to unpolarised detection.

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Content [Microstructure Fabrication Methods]