Technologies to make a microfluidic chip — Pierre Joseph (LAAS-CNRS, Toulouse, France)
Microfluidics recent overwhelming development is strongly related to the emergence and multiplication of techniques for realizing microchannels at low cost with a large range of materials, design and dimensions. I will present the basis of an important subset of these technologies, involving mainly the use of polymers. I will first detail the most popular and widely used realization of devices in PDMS (Poly-DiMethyl-Siloxane): basics (master fabrication, casting and bonding of the PDMS) and more sophisticated approaches (multilevel fabrication, active elements, permeability to pump or concentrate solutions)... I will then discuss alternative materials: silicon-based realization of microchannels and the different approaches with other polymers (replication methods, lamination-based processes, layered paper). Openings to 3D microfluidics, nanofluidics, or “microfluidics for microfabrication” will finally by presented.
The lecture will present the basics of flows at small scales: laminar flows, mixing and droplet-based microfluidics. Even if flows at small scales seems a priori simple to model, we will see that complex behaviors can emerge due to the increase of the surface/volume ratio. Some examples of applicative realizations will illustrate the lecture.
During this course, we will present the basic concept of optical microscopy, from the main optical components making up a microscope to the principle of image formation. We will then present the main imaging modalities that can be performed with an optical microscope. First we will focus on imaging modalities without labelling such as bright-field and phase contrast microscopy. We will then focus on fluorescence microscopy and present state of the art techniques ranging from epi-fluorescence microscopy to light sheet fluorescence microscopy and we will highlight approaches used to probes molecules dynamics. Finally, we will present the recent developments that have enabled to overcome the diffraction of light achieving spatial-resolution down to the molecular level.
Advanced lectures
Click on the title to see the abstract.
Droplets, High Throughput, from cells on chip to spheroids — Jean-Christophe Baret (CRPP, Bordeaux, France)
To be announced
Mass Transport at small-scale, porous media, filtration — Jeffrey Morris (City College of CUNY, New-York, USA)
Fluidic transport phenomena in nano-confined environment display rich and specific properties associated with the cross-over between confinement scales and scales associated with surface interactions. Almost frictionless flows, unexpected osmotic transport, cross-coupled effects and energy transduction, concentration or depletion effects are all examples of striking phenomenologies that raise large expectation for applications but also fundamental challenges. In this short lecture, we will present the basic framework for addressing nanofluidic phenomena, and go through a description of selected examples illustrating both the advances and open questions of this fascinating field.
We are all aware that acoustic waves are generated by moving/hitting objects such as in music instruments. The reverse, motion generated by acoustic waves, is less known… In this presentation we will give the secrets to master acoustic waves in order to: (i) push objects at a distance (using radiation forces) (ii) create swirls and strong flows (using acoustic streaming). Examples will be given in a microfluidic scenery, where these effects are extremely powerful.
Microfluidics as an essential tool for understanding and enabling sensing of analytes in sweat — Jason Heikenfeld (CEAS, Cincinnati, USA)
A number of significant challenges have historically kept sweat from its place in the pantheon of clinical samples. This talk reviews the most pressing challenges for sweat biosensing, and highlights emerging breakthroughs which will likely change your perspective on what sweat biosensing can accomplish. Many of these breakthroughs are the result of innovations with microfluidics. Furthermore, microfluidics has played an important role in understanding how analytes partition into sweat, and how those analytes are then transported to the surface of the body. This talk will also review how this university technology has been commercialized into a startup company, a startup company that is now listed by Bloomberg as one of the top 50 most promising startups world-wide.
Single cell and vesicle analysis on microfluidic devices — Petra Dittrich (ETH Zurich, Suisse)
Single-cell analysis is an emerging research field which is relevant for fundamental studies in cell adaptation and evolution (e.g. development of stem cells) as well as for applications in the medical and diagnostic fields (e.g. emergence of cancer or the occurrence of antibiotic resistance in bacterial populations). However, single-cell analysis is facing numerous challenges due to limitations in the available analytical methods. The current gold standards of single-cell analysis include cytometry and fluorescence activated cell sorting (FACS) for ultrafast analysis of large cell populations, and conventional fluorescence microscopy for analysis of living cells over longer periods. Recently, the emergence of microfluidic platforms has promised novel analytical strategies for positioning, treatment and observation of single cells. Several studies demonstrated the potential of microdevices for the analysis of DNA or RNA derived from single cells, e.g. in combination with polymerase chain reaction (PCR) to enhance the sensitivity of the measurements. When targeting proteins and metabolites, the analysis gets far more difficult due to the lack of suitable amplification methods, the large number of different compounds present, and their variations in chemical nature and hence, the quantitative analysis of intracellular biomolecules remained difficult. Recently, we introduced a general method to quantify intracellular compounds down to a few zeptamoles by combining microfluidic cell trapping and isolation with the analytical power of immunoassays, specifically enzyme-linked immunosorbent assays (ELISAs). We use a two-layer microfluidic device made of PDMS that comprises an array of up to a few hundred microchambers, each encapsulating a volume of a few hundred picoliters. Cells are trapped individually in microsized hurdle structures placed in the center of a microchamber and can be repeatedly treated and washed before lysis. We employed this device for quantifying intracellular proteins, enzymes and other (small) molecules in healthy cells as well as cells treated with chemical compounds. Furthermore, modifications of the platform allows for analysis of yeast and bacteria lysates and studies on cell membrane fusion. These microfluidic platforms proved highly useful for analysis of cell models, i.e. giant unilamellar vesicles (GUVs), which we create in order to elucidate processes at the membrane. We could address questions of membrane permeability and membrane fusion. In addition, we could gain new insights into the properties of membranes, when exposed to mechanical forces. Together, these studies may reveal in more detail the role of the membrane in the cellular response to chemical stimuli and mechanical strains. The first part of the lecture will give a general overview of the current microfluidic platforms, and discuss limitations and open challenges. The second part of the lecture will focus on single cell and vesicle analysis in small microchambers that we developed in the recent years the Bioanalytics Group at ETH Zurich.
Blood on chip: from molecular to cellular analysis —Stéphanie Descroix (Institut Curie, Paris, France)
The development of precision medicine and the multiplication of targeted therapies, call for major progress in analytical methods, allowing increased multiplexing and the implementation of more complex decision trees, without cost increase or loss of robustness. In this context, Microfluidics has emerged as a disruptive technology as it has allowed tremendous progress in particular for circulating biomarkers detection and analysis. In this lecture, we will focus on microfluidic development for circulating biomarkers analysis in the context of cancer diagnosis and prognosis. In particular, both monophasic and biphasic microfluidic formats will be considered and a specific focus will be made on the combination of magnetic particles and microfluidics for blood analysis.
Blood on chip: biomimetic systems, blood cell biomechanics —Olivier Théodoly (Laboratoire Adhésion et Inflammation, Marseille, France)
To be announced
Organs on chip: Neurones — Vincent Studer (IINS, Bordeaux, France)
To be announced
Building artificial microniches — Virgile Viasnoff (BMC3, Singapore et CNRS)
In this talk I will review some of the recent advances of how biomimetic interfaces can be organize in space to create artificial microniches for cell culture. I will review how such microfabricated surfaces are used to i- understand cell response to environmental changes, ii- to create structured organ on chips and iii- how new types of cell based behavioral assays. I'll discuss the advantages and drawbacks of microfluidics approaches in this context. Technical and scientific challenges will also be discussed.
Microfluidics for advanced materials — Jacques Leng (LOF, Bordeaux, France)
In this lecture, I will give a short overview of the interplay between microfluidics and material science. Small-scale flows are especially interesting because they provide an excellent control on mass and heat transfers, which are at the heart of material genesis (i.e. crystallization, gelation, chemical reactions such as polymerisation, etc.). Final materials are mostly (nano to micro) particles or fibres with advanced shapes and functionalities due to the versatility offered by lab-on-chips.
3D printing, tissue engineering — Raphaël Devillard (BIOTIS, INSERM, Bordeaux)
