Vincent Studer

Microfluidic large scale integration

We developed high-density microfluidic chips that contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large-scale integration. A key component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. We used these integrated microfluidic networks to construct the microfluidic analog of a comparator array and a microfluidic memory storage device whose behavior resembles random-access memory.

A nanoliter-scale nucleic acid processor with parallel architecture

The purification of nucleic acids from microbial and mammalian cells is a crucial step in many biological and medical applications. We have developed microfluidic chips for automated nucleic acid purification from small numbers of bacterial or mammalian cells. All processes, such as cell isolation, cell lysis, DNA or mRNA purification, and recovery, were carried out on a single microfluidic chip in nanoliter volumes without any pre- or postsample treatment. Measurable amounts of mRNA were extracted in an automated fashion from as little as a single mammalian cell and recovered from the chip. These microfluidic chips are capable of processing different samples in parallel, thereby illustrating how highly parallel microfluidic architectures can be constructed to perform integrated batch-processing functionalities for biological and medical applications.

Scaling properties of a low-actuation pressure microfluidic valve

Using basic physical arguments, we present a design and method for the fabrication of microfluidic valves using multilayer soft lithography. These on-off valves have extremely low actuation pressures and can be used to fabricate active functions, such as pumps and mixers in integrated microfluidic chips. We characterized the performance of the valves by measuring both the actuation pressure and flow resistance over a wide range of design parameters, and compared them to both finite element simulations and alternative valve geometries.

An integrated AC electrokinetic pump in a microfluidic loop for fast and tunable flow control

We have built a dedicated lab on a chip to study the performance of an integrated electrokinetic micropump, driven by a low voltage AC signal. This micropump consists of an array of interdigitated electrodes and is here integrated in a microfluidic loop. We demonstrate that this device can pump continuously and reproducibly electrolyte solutions of low to moderate ionic strength. The pumping speed reaches up to 500 [micro sign]m s(-1) in 20 [micro sign]m deep and 100 [micro sign]m wide channels with a driving signal in the 1-10 kHz range and an amplitude of only a few volts. In addition, we have observed an interesting reversal of the pumping direction at higher frequencies (50-100 kHz). Our device permits a systematic and automated exploration of the influence of the ionic strength thanks to an integrated micromixer.

Compressive fluorescence microscopy for biological and hyperspectral imaging

The mathematical theory of compressed sensing (CS) asserts that one can acquire signals from measurements whose rate is much lower than the total bandwidth. Whereas the CS theory is now well developed, challenges concerning hardware implementations of CS-based acquisition devices—especially in optics—have only started being addressed. This paper presents an implementation of compressive sensing in fluorescence microscopy and its applications to biomedical imaging. Our CS microscope combines a dynamic structured wide-field illumination and a fast and sensitive single-point fluorescence detection to enable reconstructions of images of fluorescent beads, cells, and tissues with undersampling ratios (between the number of pixels and number of measurements) up to 32. We further demonstrate a hyperspectral mode and record images with 128 spectral channels and undersampling ratios up to 64, illustrating the potential benefits of CS acquisition for higher-dimensional signals, which typically exhibits extreme redundancy. Altogether, our results emphasize the interest of CS schemes for acquisition at a significantly reduced rate and point to some remaining challenges for CS fluorescence microscopy.

Fabrication of microfluidic devices for AC electrokinetic fluid pumping

Two techniques for the fabrication of novel microfluidic devices for electrokinetic fluid pumping are presented. Both consist of forming a micro-channel and reservoirs on a transparent cover sheet and patterning an array of interdigitated asymmetric micro-electrodes on a flat substrate. The two techniques differ from each other in their building materials as well as the pattern replication technique used for the cover sheet fabrication. In the first approach, we used a glass substrate for the electrode fabrication and casting of an elastomer for the cover sheet. In the second approach, both cover sheet and substrate are obtained by imprinting plastic pellets on a pre-patterned or flat mold. In assembled devices, pumping has been demonstrated and characterized by optical microscopy. The observed dependence of the pumping velocity on applied voltage and frequency are in line with theoretical predictions.

Nanoembossing of thermoplastic polymers for microfluidic applications

We present a method for the fabrication of plastic microfluidic devices based on nanoembossing and thermal bonding. By nanoembossing of thermoplastic polymer pellets, both microfluidic deep channels and high resolution features can be formed using a silicon mold fabricated by electron beam lithography and reactive ion etching. By thermal bonding with another plastic sheet, the fabricated microfluidic devices can be sealed without clogging. Observation of pressure driven and electrokinetic flows through high density pillar arrays indicates the feasibility of nanofluidic analysis using plastic devices.

Nanoimprint lithography for the fabrication of DNA electrophoresis chips

We describe the fabrication of microfluidic devices for bio-molecule separation using an array of well-defined nanostructures. Two types of pattern replication of the same device configuration are considered, based on different material processing. In the first approach we use a tri-layer nanoimprint lithography process to pattern a silicon dioxide substrate, on top of which we stick a transparent elastomer cover plate. The second approach relies on direct imprinting of thermoplastic polymer pellets to form two bulk plastic plates later assembled together by thermal bonding. As a result, novel microfluidic devices combining deep and wide channels and a shallower nanostructure array are obtained. The fabricated devices have been characterized by epifluorescence microscopy, using a fluorescein solution to track fluid penetration inside the high density nanostructured region. These realisations not only demonstrate that nanofluidic devices are achievable, but also that they can be manufactured for mass production via nanoimprint-based techniques.

3D high- and super-resolution imaging using single-objective SPIM.

Single-objective selective-plane illumination microscopy (soSPIM) is achieved with micromirrored cavities combined with a laser beam–steering unit installed on a standard inverted microscope. The illumination and detection are done through the same objective. soSPIM can be used with standard sample preparations and features high background rejection and efficient photon collection, allowing for 3D single-molecule-based super-resolution imaging of whole cells or cell aggregates. Using larger mirrors enabled us to broaden the capabilities of our system to image Drosophila embryos.

Active connectors for microfluidic drops on demand

We introduce a simple and versatile microfluidic drop-on-demand solution that enables independent and dynamical control of both the drop size and the drop production rate. To do so, we combine a standard microfluidic T- junction and a novel active switching component that connects the microfluidic channel to the macroscopic liquid reservoirs. Firstly, we explain how to make this simple but accurate drop-on-demand device. Secondly, we carefully characterize its dynamic response and its range of operations. Finally, we show how to generate complex two-dimensional drop patterns dynamically in single or multiple synchronized drop-on-demand devices.