Frederik Ceyssens

A versatile electrowetting-based digital microfluidic platform for quantitative homogeneous and heterogeneous bio-assays

Electrowetting-on-dielectric (EWOD) lab-on-a-chip systems have already proven their potential within a broad range of bio-assays. Nevertheless, research on the analytical performance of those systems is limited, yet crucial for a further breakthrough in the diagnostic field. Therefore, this paper presents the intrinsic possibilities of an EWOD lab-on-a-chip as a versatile platform for homogeneous and heterogeneous bio-assays with high analytical performance. Both droplet dispensing and splitting cause variations in droplet size, thereby directly influencing the assays performance. The extent to which they influence the performance is assessed by a theoretical sensitivity analysis, which allows the definition of a basic framework for the reduction of droplet size variability. Taking advantage of the optimized droplet manipulations, both homogeneous and heterogeneous bio-assays are implemented in the EWOD lab-on-a-chip to demonstrate the analytical capabilities and versatility of the device. A fully on-chip enzymatic assay is realized with high analytical performance. It demonstrates the promising capabilities of an EWOD lab-on-a-chip in food-related and medical applications, such as nutritional and blood analyses. Further, a magnetic bio-assay for IgE detection using superparamagnetic nanoparticles is presented whereby the nanoparticles are used as solid carriers during the bio-assay. Crucial elements are the precise manipulation of the superparamagnetic nanoparticles with respect to dispensing and separation. Although the principle of using nano-carriers is demonstrated for protein detection, it can be easily extended to a broader range of bio-related applications like DNA sensing. In heterogeneous bio-assays the chip surface is actively involved during the execution of the bio-assay. Through immobilization of specific biological compounds like DNA, proteins and cells a reactive chip surface is realized, which enhances the bio-assay performance. To demonstrate this potential, on-chip adhesion islands are fabricated to immobilize MCF-7 human breast cancer cells. Viability studies are performed to assess the functionalization efficiency.

Biofunctionalization of electrowetting-on-dielectric digital microfluidic chips for miniaturized cell-based applications

In this paper we report on the controlled biofunctionalization of the hydrophobic layer of electrowetting-on-dielectric (EWOD) based microfluidic chips with the aim to execute (adherent) cell-based assays. The biofunctionalization technique involves a dry lift-off method with an easy to remove Parylene-C mask and allows the creation of spatially controlled micropatches of biomolecules in the Teflon-AF(®) layer of the chip. Compared to conventional methods, this method (i) is fully biocompatible; and (ii) leaves the hydrophobicity of the chip surface unaffected by the fabrication process, which is a crucial feature for digital microfluidic chips. In addition, full control of the geometry and the dimensions of the micropatches is achieved, allowing cells to be arrayed as cell clusters or as single cells on the digital microfluidic chip surface. The dry Parylene-C lift-off technique proves to have great potential for precise biofunctionalization of digital microfluidic chips, and can enhance their use for heterogeneous bio-assays that are of interest in various biomedical applications.

A high aspect ratio SU-8 fabrication technique for hollow microneedles for transdermal drug delivery and blood extraction

Protein drugs, e.g. hormonal drugs, cannot be delivered orally to a patient as they get digested in the gastro-intestinal (GI) tract. Thus, it is imperative that these kinds of drugs are delivered transdermally through the skin. To provide for real-time feedback as well as to test independently for various substances in the blood, we also need a blood sampling system. Microneedles can perform both these functions. Further, microneedles made of silicon or metal have the risk of breaking inside the skin thereby leading to complications. SU-8, being approved of as being biocompatible by the Food and Drug Agency (FDA) of the United States, is an attractive alternative because firstly it is a polymer material, thereby reducing the chances of breakages inside the skin, and secondly it is a negative photoresist, thereby leading to ease of fabrication. Thus, here we present very tall (around 1600 µm) SU-8 polymer-based hollow microneedles fabricated by a simple and repeatable process, which are a very good candidate for transdermal drug delivery as well as blood extraction. The paper elaborates on the details that allow the fabrication of such extreme aspect ratios (>100).

Creating multi-layered structures with freestanding parts in SU-8

This paper reports on a new method to create multi-layered structures with freestanding parts in SU-8. Examples of such structures are beams partially resting on a post or microchannels. The method, based on high-absorption UV light with a wavelength of 313 nm in SU-8, is fast, uses only traditional micromachining equipment and requires very few processing steps. It is well suited for thin freestanding layers (<15 µm). Furthermore, a variant of a method that uses a built-in UV blocking layer to enable freestanding structures is described in detail. This method has a broader application range in terms of the thickness of the freestanding parts. Both methods are applied to the fabrication of optical fiber clamps.

A PDMS lipseal for hydraulic and pneumatic microactuators

Recent publications show that hydraulic and pneumatic microactuators offer superior power and force densities at the microscale. The main technological barrier for the development of these actuators is the lack of microseal technologies. These seals must prevent the driving fluid leaking to the outside world without introducing friction. This paper presents a method to fabricate miniature lipseals in batch quantities. A simulation method for the design of these seals is developed and validated experimentally. Hydraulic and pneumatic actuators comprising lipseals have been fabricated and tested. These prototype actuators have an outside diameter of 1.5 mm, and were able to generate forces of 1.2 N at a supply pressure of 1.6 MPa.

A Low-Cost and Highly Integrated Fiber Optical Pressure Sensor System

This paper presents a simple fiber-optic based pressure measurement system, in which both sensor and readout parts are constructed using batch micromachining techniques, supplemented with some straightforward assembly steps. Prototypes of relative and absolute pressure sensors parts and a readout part have been realized. Goal of this research is to enable deployment of such harsh environment sensors in high-volume, low-cost applications.

Microsized Piston-Cylinder Pneumatic and Hydraulic Actuators Fabricated by Lithography

Future microrobotic applications require actuators that can generate a high actuation force in a limited volume. Up to now, little research has been performed on the development of pneumatic or hydraulic microactuators, although they offer great prospects in achieving high force densities. In addition, large actuation strokes and high actuation speeds can be achieved by these actuators. This paper describes a fabrication process for piston-cylinder pneumatic and hydraulic actuators based on etching techniques, UV-definable polymers, and low-temperature bonding. Prototype actuators with a piston area of 0.15 mm2 have been fabricated in order to validate the production process. These actuators achieve actuation forces of more than 0.1 N and strokes of 750 mum using pressurized air or water as driving fluid.

Deep etching of glass wafers using sputtered molybdenum masks

This note presents a simple, low-cost technology to fabricate very deep isotropically etched features in glass wafers. A process based on fast etching glass combined with a stress-optimized molybdenum mask layer and a photoresist was found to be very suitable for such purposes. The obtained performance, up to 1.2 mm deep etching, rivals the best existing techniques while being more cost-competitive and using widely available equipment.

An optical absolute pressure sensor for high-temperature applications, fabricated directly on a fiber

Fiber optical pressure sensors show great promise in monitoring harsh environments as sensitive readout electronics can be located remotely. In this paper, a process based on thin film techniques and focused ion beam (FIB) machining is demonstrated that allows the fabrication of a Fabry–Perot interferometer-based sensor directly on top of an optical fiber. Besides its extremely small size and rugged monolithic construction, the silica-based sensor has the advantage that thermal mismatch is minimal and a vacuum reference pressure cavity is present, enabling application in high-temperature environments. Operation in an environment up to 600 °C is demonstrated. Furthermore, a possible route toward mass fabrication of such sensors is presented, avoiding the need for a FIB operation.

An ionic liquid based strain sensor for large displacement measurement

A robust and low cost ionic liquid based strain sensor is fabricated for high strain measurements in biomedical applications (up to 40 % and higher). A tubular 5 mm long silicone microchannel with an inner diameter of 310 µm and an outer diameter of 650 µm is filled with an ionic liquid. Three ionic liquids have been investigated: 1-butyl-1-methylpyrrolidinium bis (trifluoromethylsulfonyl) imide, ethylammonium nitrate and cholinium ethanoate. When the channel is axially stretched, geometrical deformations change the electrical impedance of the liquid channel. The sensors display a linear response and low hysteresis with an average gauge factors of 1.99 for strains up to 40 %. Additionally, to fix the sensor by surgical stitching to soft biological tissue, a sensor with tube clamps consisting of photopatternable SU-8 epoxy-based resin is proposed.