TECHNOLOGY UNIT: BIOLOGICAL MICROSYSTEMS & ADVANCED OPTICS ENGINEERING
Microfluidic systems implementation & optical characterization
At microscale, flow regimes are very predictable, in contrast to the chaotic behaviour of the turbulent flow that occurs at our scale.New technologies enable simplified manipulation of microscopic objects as well as the reduction of reagent quantities, opening possibilities for a wide variety of applications in the fields of microbiology, medical diagnostics and chemical analysis.Moreover, any assay or diagnostic tool requires an automated readout technique. The smaller the size of the object to observe, the more sensitive and specific the readout technique must be. Nowadays, highly-sensitive and advanced optical microscopies and spectroscopies give access to morphological, structural and/or chemical information about biological cells, characterized in most cases by weak absorption and scattering of light.Microfluidics and advanced Optics can be combined to perform accurate phenotype-based or functional-based characterization of biological microsystems.
This association offers powerful analysis advantages over more classical techniques:
- Adaptability and diversity of applications
These new technologies have emerged as a very potent tool in a wide range of applications, from life science to clinical research.
Objective 1 :
Based on advanced optics, this consists in observing, without labelling, the physical and chemical characteristics of cells. Several applications have been developed in the field of immunology and bacteriological analysis. In the latter case, this technology makes it possible to accurately identify bacteria as well as characterizing their growth’s kinetics in the presence of antibiotics.
Objective 2 :
Usually experiments aiming at determining the behaviour of cells in presence of a given molecule are performed in bulk on cell cultures, focusing on the evolution of the whole sample regardless of the individuality of each cell. Our approach aims to control the external environment of each cell individually for in-vitro analysis. By doing so we are able to monitor the heterogeneity of cells within a population and highlight mechanisms that could not be observed based on the average behavior of a cluster of cells.
Objective 3 :
When performing single-cell analysis, we need to isolate each cell from the others and place it into a specific micro-environment. This process is time consuming and limits the number of cells to be studied. Our microfluidic-based technologies enable, through automated processes (controlled fluid systems, online optical measurements, image analysis algorithms), to circumvent this problem and perform high-throughput screening.
Objective 4 :
Our technologies enable to design new tools for automated sample preparation. Sometimes making the sample ready for analysis is a tedious task, for instance during cellular enrichment steps. Microtechnologies can be used to get rid of the complicated protocols and convert them into straightforward procedures, for example by removing staining steps.
Expertise, Equipment & Technologies
Our team is led by strong theoretical and practical qualifications in microtechnologies and optics, and by a desire to always dig deeper into the possibilities they offer for health-related applications. Each member possesses valuable and multidisciplinary knowledge and expertise.
Thanks to these various skills, we are able to work in the following fields:
- Continuous flow and droplet-based microfluidics
- Biosensors and point-of-care test / rapid diagnostic test
- Optical characterization: Holographic microscopy and Raman spectroscopy
- Image processing
- Design and prototyping of automated microscopes
- Cell encapsulation in droplets: We are able to create micro-droplets of cell media and encapsulated cells. Droplets act as bioreactors and enable cell characterization at single-cell level.
- Z-axis reconstruction of a bacteria: digital reconstruction of an hologram acquired from a non-stained bacteria in buffer
Technology: Droplet-based microfluidics
Droplet-based microfluidics is a helpful tool when it comes to single-cell analysis. The principle is to send immiscible oil flows perpendicular to an aqueous flow containing the cells. This results in the compartimentalization of the media into cell-containing droplets. Droplets act as microbioreactors providing the cells with all the nutrients they need to remain viable. Microfluidics techniques allow high-throughput generation of monodisperse droplets, hence giving the possibility to analyze a large number of individual cells and related micro-environment via various types of imaging or spectroscopic techniques, in a static configuration or in a dynamic flow.
A workflow including droplet-based microfluidics and a cell sorter has been developed to enable ultra-High-Throughput droplet sorting. This pipeline can be used to perform ultra-High-Throughput Screening of bacteria.
Technology: Holographic Microscopy
Digital Inline Holographic Microscopy is a label-free, simple and robust technic. It consists in out-of-focal-plane imaging of weakly scattering micro-objects through a microscope objective, while using a monochromatic light source. Patterns of interference are recorded on a single image called hologram. Contrast enhancement is obtained after real-time digital refocusing of the single acquired hologram, using proper light propagation algorithm.
Technology: Raman Micro-spectroscopy
At BIOASTER, a highly-sensitive Raman micro-spectrometer has been optimized to allow for the characterization of micro-organisms at the single cell level. Moreover, phenotype-based assays and tests can be performed by monitoring spectral changes under, for instance, chemical cues.
- Participation in the AFC 22nd annual congress
- Results presentation at ISCB2018 and the 6th Annual Single Cell Analysis Congress 2018