CNRS UMR 8231 Chimie Biologie Innovation (CBI)
Patrick Tabeling's research interests focus on a wide range of subjects involving the use of microfluidic technology such as, but not limited to, paper microfluidics for low-cost diagnostics, the fabrication of stimuli-responsive hydrogels for single cell or nucleic acid amplification tests, the fabrication of new photonic materials, the modeling of colloidal deposition as precursor to the clogging phenomenon, the plugging of sudoral pores by aluminum salts, and the controlled delivery of peptides through encapsulation using double emulsions.
P. Garneret, E.Coz, P. Tabeling
(in collaboration with Institut PASTEUR)
Lab on a Chip, 2017
Scientific Reports 2017
The detection of pathogens and the monitoring of the corresponding medical treatments is entering an interesting phase: new technological approaches are emerging, with a serious potential for revolutionizing the field. This is the case for technologies based on the combination of isothermal amplification of Nucleic Acids (NA) and paper microfluidics.
This combination makes it possible to obtain, on the same device, outstanding analytical performances (single molecule sensitivity, high selectivity), along with extremely low costs, storage, fast response, small volumes, multiplexing and disposability. With such a coupling, it becomes conceivable to perform early diagnostics and surveillance of pathogens in the field, following a pathway recently opened by the two teams proposing the project (Scientific Reports, 7, 1347 (2017)) along with monitor the treatment of diseases in remote places, a possibility unconceivable until now. Today, we are at an early stage of development of the approach. Progress in the area is swift but fragmental and there exist serious bottlenecks.
The goal of MMN, together with PASTEUR (J. C Manuguerra's team), is to unlock them and realize complete systems, from the sample to the readout. The potential impact is considerable. It concerns the precocious detection of pathogens (virus, bacteria, parasite) in humans, animals, water and air, the monitoring of therapies, the analysis of resistance to antibiotics in remote areas, today inaccessible to the existing technologies. Would early nucleic acid detections of pathogens be possible in cowsheds, water ponds or small villages in low settings environments, the occurence and propagation of diseases would seriously be reduced. Would continuous monitoring of contagious diseases spread across vast countries, their eradication would become posssible.
Cover page of Lab on a Chip (March 2017) illustrating the concept of paper microfluidics for the multiplexed detection, with Nucleid Acid Amplification, of contagious diseases on paper.
Photonic Materials made with Microfluidics
I. Maimouni, M. Russo, M. Morvaridi, J. Ricouvier, P. Yazhgur, P. Tabeling
(collaboration MICROFLUSA European Union Horizon 2020 FET OPEN 2)
PRL 2017, Lab on a Chip 2017
The experimental system producing hyper uniform bidisperse droplets, and images showing, for two size ratios, the presence of crystallized zones (PRL, 2017).
Creating new materials, with photonic properties (such as opening complete band gaps) has challenged the colloidal community for decades. With the support of a European project (MICROFLUSA), involving three universities (TECHNION, KTH), we address this challenge with microfluidic technology.
We have demonstrated that it is possible to produce elementary clusters of droplets (builiding blocks of future materials), with controlled morphologies (trimers, diamond, tetrahedrons, pentahedrons,...), and solidify them, directly in a microfluidic device. More recently, we focus on disordered materials. We have shown that disordered bidisperse assemblies of droplets exhibit hyperuniform properties, that can be optimized (J.Ricouvier et al, PRL, Dec 2017). We follow this line of thought by assembling, directly in microfluidic devices, 2D and 3D droplet-based structures that, despite their disorder, are good candidates for opening band gaps. We hope, in this manner, to create self-assembled disordered materials with band gaps, in a wide range of wavelenghts, i.e from the visible to the THz. This work is carried out with numerical simulations performed at Technion University (Israel).
Thermo actuated valves and microcages
H. Geisler, M. Abdorahim, F. Monti, P.T abeling
Microsystem and Microengineering 2017
The concept of using stimuli-responsive hydrogels to actuate fluids in microfluidic devices is particularly attractive, but limitations, in terms of spatial resolution, speed, reliability and integration, have hindered its development during the past two decades.
By patterning and grafting poly(N-isopropylacrylamide) PNIPAM hydrogel films on plane substrates with a 2 μm horizontal resolution and closing the system afterward, we have succeeded in unblocking bottlenecks that thermo-sensitive hydrogel technology has been challenged with until now. In this paper, we demonstrate, for the first time with this technology, devices with up to 7800 actuated micro-cages that sequester and release solutes, along with valves actuated individually with closing and opening
switching times of 0.6 ± 0.1 and 0.25 ± 0.15 s, respectively.
Two applications of this technology are illustrated in the domain of single cell handling and the nuclear acid amplification test (NAAT) for the Human Synaptojanin 1 gene, which is suspected to be involved in several neurodegenerative diseases such as Parkinson’s disease. The performances of the temperature-responsive hydrogels we demonstrate here suggest that in association with their moderate costs, hydrogels may represent an alternative to the actuation or handling techniques currently used in microfluidics, that is, pressure actuated polydimethylsiloxane (PDMS) valves and droplets.
(A) Sequences of fluid injections and temperature changes for a system of 25 hydrogel cages, 200 × 200 μm in size with 10 μm thick walls, in a microfluidic chamber with a dimension of 1 cm × 2.5 mm × 10 μm along with the topographic images of a similar system including four cages. A fluorescein solution is driven through the system with walls in a low position (temperature held at 50 °C) (a), with raised walls touching the upper wall of the chamber (b). The system is washed by water while fluorescein is isolated in the closed chambers (c). (B) Temporal increase of the fluorescence signal I/Imax ((blue line—see text) in a rectangular cage as fluorescein diffuses through the walls.(C) System similar to (A), Caging-functioning system with 3000 circular walls represented at various scales. The right figure shows fluorescein (white) trapped in the circular walls (black) in water (gray). The diameters of the cages are 100 μm, and the walls are 25 μm wide. The density is 44 cages per mm2.
Particle deposition kinetics
C.M. Cejas, F. Monti, J.P. Burnouf, P. Tabeling
(in collaboration with SANOFI)
Physical Review E 2018
The universal diagram of particle deposition represented as an advection-diffusion component in the y-axis, dimensionless number showing strength of van der Waals forces with respect to electrostatic forces in the x-axis. There are three principal deposition regimes: Diffusive (diffusion), van der Waals (adhesion) and Debye (electrostatic).
Using microfluidic experiments, we describe the deposition of weakly Brownian particles transported in a straight channel by a liquid at small Reynolds numbers under conditions of high ionic strengths. Our studies fall in a regime where particle-wall van der Waals interactions govern the deposition mechanism. We analytically calculate the concentration profiles, retention profiles, and deposition kinetics for a wide extent of physical parameters (velocity, geometry, surface properties, concentration) and also conducted numerical simulations based on Langevin equations.
We find that the theory agrees with numerical simulations, which both confirm the experimental results. From this analysis, we demonstrate a universal dimensionless deposition function described by contributions from advection-diffusion transport and adhesion forces (Hamaker constant). Results show that we accurately confirm the theoretical expression for the deposition kinetics.
We explain quantitatively the deposition kinetics of individual colloidal particles, along with their corresponding retention profiles. The model reproduces the experimental observations remarkably well, within a broad range of parameters, extending our previous work in Langmuir. In the present work, we thus succeeded to establish a universal diagram of particle deposition, thus far lacking in the literature. This diagram could prove a useful guide in not just predicting deposition behavior, but also in adapting different physical parameters for various targeted applications. The ad- vantage of the universal diagram is that it provides a paradigm to fine-tune physical parameters to allow one condition to dominate over the other.
The mechanism of plugging of sudoral pores by aluminium salts
Y. Sakhawoth, F. Monti, J.B. Galey, P. Tabeling
(in collaboration with L'ORÉAL)
Aluminum salts are broadly used in cosmetics for antiperspirants. The action of the antiperspirant is based on the plug in the eccrine pores, that blocks the flow of the sweat. This mechanism is not fully understood yet.
At the MMN lab we have designed a microfluidic chip mimicking an eccrine sweat pore by using a T-junction geometry. We use this device to study the dispersion of ACH (Aluminum Chlorohydrate) in an artificial sweat pore.
In certain conditions, we observe the formation of aggregates at the T-Jonction in the sweat channel.
The project is to investigate the phenomena with X-Ray and other techniques in order to understand the structure and composition of the plugs.
How to deliver peptides in a controlled manner ?
M. Truchet, J.P. Burnouf, P. Tabeling
(in collaboration with SANOFI)
Peptide therapeutics have a growing significance in pharmaceutical and biotech industry due to their selectivity, potency and low toxicity. They are widely used to treat chronic diseases. However most peptides degrade quickly in the body. To avoid daily injection we encapsulate the active pharmaceutical ingredients (API) to control their release over several days or weeks.
In this study, the combination of standard methods and microfluidics technologies is used to prepare double emulsions and then microspheres entrapping hydrophilic compounds.
We are developing a three-step process allowing for the production of double emulsion droplets and then, after solidification, microspheres with controlled properties (morphology, shape, size, peptide content…).
A figure showing the device along with the structures we are currently obtaining, is shown on the right.