Parcours Nanobiotechnologies 2e année

This course will be focused on the main nanofabrication and characterization techniques used in clean-rooms in research laboratory and semi-industrial environments for the fabrication of current and future semiconductor devices. It will combine regular lectures and a practical training on nanobiotechnology in clean room facilities.

Outline
This course will include a first part covering the main nanofabrication and characterization techniques used in clean-rooms and
a second part dedicated to a practical training.

• The first part will be taught as regular lectures. The principles of these techniques will be presented and illustrated through concrete examples obtained in the clean-rooms of the Minatech Campus in Grenoble. This course will provide you with the basics of technological steps, thin film deposition techniques, lithography processes, and advanced characterization used during the fabrication of single devices up to their large-scale integration.
• The practical training (second part) will consist in the construction of a micro-patterned device using state-of-the art microfabrication techniques. Fluorescently marked cells will be deposited on the constructed micropatterns and different cell.

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Goal

The applications of surface functionalization are multiple and cover large fields. The aim of this course is to focus on two challenging applications: the conception of biosensors and (photo)electrocatalysis. The course is structured into two modules differentiated by the types of application.

1.    Surface functionalization for the fabrication of biosensors (12h)

• Functionalization and electrofunctionalization (AS)
• Applications to olfactory biosensors and biomimetic electronic noses (YHB)
• Application to the conception of cell chips and detection of bacteria (YR)
• Biomolecular assemblies and self-organization of biomolecules on surfaces (DG, PHE)

2.    (Photo)electrocatalysis applications (12h)

• Introduction to (photo)electrocatalysis (VA)
• Molecular engineering of nanomaterials for (bio)electrocatalysis in energy-related sytems (AL)
• Surface functionalization for photo(electro)catalysis: from photovoltaics to solar water splitting and CO2 conversion (BR, DA)
• Micro/nanostructure in electrocatalysis (PC)

The sessions will be given by a series of experts in the field. The teachers will coordinates to focus especially on the most essential aspect of functionalization, such as grafting stability, mastering distance between graft and surface, ensuring optimal electronic transfer, passivation, ecofriendliness. Particularly for biosensors, the surface chemistry should allow to maintain the integrity of the grafted biomolecules or biological objects.
Part of the sessions will be devoted to critical analysis of some selected literature papers in detail and sorting out the functionalization strategies and its consequences.

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Nanotechnologies give access to new and interesting properties of materials. Applications or potential applications of nanomaterials are today very numerous in research, industrial processes but also everyday life. As a consequence, impact on health and safety of those new substances becomes important. Indeed, assessment on life cycle analysis is a key element of development. This course presents the current knowledge and research regarding the potential risks associated to the development of nanotechnologies, organized around 3 axes:

• Toxicology and ecotoxicology current knowledge, thanks to presentation of latest scientific studies on the subject,
• occupationnal potential risks : how to manage an emerging risk ? what’s mandatory ? what kind of metrology can we use ? what are the best practices in order to prevent impact on health and environment ?
• social perception of nanotechnologies over the world and over different cultures.

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The Second year Research Training can take two different forms:

- 10 half-days spent in identified labs on recurrent subjects proposed by the coordinator of the teaching unit ;

- a part-time internship in a lab of the Grenoble area, representing more or less 1 day each week during a semester. In can be on the same subject as the M1 internships and/or of the future M2 internships, allowing a continuous immersion in a laboratory on a given for the whole duration of the master program. Students joining the program in M2 can also follow this program but they must readily find a welcoming lab by themselves prior to their arrival in Grenoble or at the very beginning of the academic year.

In both cases, the module is evaluated through a short report followed by an oral examination, in which students expose their research objectives, implementation, and results, and answer to the questions of the jury.

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Introduction à la biologie structurale, Introduction à différentes techniques de microscopie électronique et préparation des échantillons, diffusion aux rayons X des macromolécules, cristallographie macromoléculaire, Principes de la Résonance Magnétique Nucléaire et détermination de la structure biomoléculaire.

Introduction to structural biology, Introduction to different electron microscopy (EM) techniques to study cells (TEM/SEM) and sample preparation, X-ray scattering by macromolecules, Macromolecular crystallography, Nuclear Magnetic Resonance principles and key steps for structure determination of biomacromolecules

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Goal: The aim of this class is to discover natural materials that form our tissues in the body and to understand what are the current progresses and challenges in the field of implantable biomaterials. We will also focus on the modification of surface properties of biomaterials in terms of chemistry, topography and mechanical properties. The main steps of inflammatory reaction after implantation of a biomaterial will be reviewed. We will then discover the current products and major advances in the field of cardio-vascular implants and orthopedic biomaterials. Finally, we will present the concepts and methods used in tissue engineering.

Content:
1) Structure of natural materials : Building blocks at different length scales

• Cell / Extracellular matrix proteins / Polysaccharides
• Interaction of a cell with its environment / Adhesion
• Stem cells, concept of niche (gradients, position, mechanics)
• Examples of organization of some tissues (vascular wall, cartilage, bone)
• Example of peculiar properties of natural materials : superhydrophobicity, silk and super-strong adhesion

2) Overview of implantable biomaterials

• Definition, History
• Different types of biomaterials (metals, ceramics, synthetic polymers, and biopolymers)
• Concept of tissue engineering and regenerative medicine

3) Importance of surface properties : from fundamental studies to applications

• Chemistry (presence of specific receptors, growth factors)
• Micro and nano-topography
• Mechanical properties

4) Reaction against a foreign body

• Foreign body reaction
• Inflammatory cells
• Biocompatibility tests
• Development/regulatory issues

5) Design and function of cardiovascular implants

• Stents
• Vascular Grafts

6) Biomaterials for orthopaedic applications

• Different needs in orthopaedics
• Titanium
• Metallic alloys
• Ceramics as bone grafts

7) Tissue engineering / Stem cell and precursor cell-based therapies

• Different types of stem cells and their potential
•  Analysis of transcription factors
• Expression of proteins to assess cell differentiation

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Goal: From the sequencing and electronic analysis of single molecules, to waste water treatment, desalinisation, or osmotic energy harvesting, , nanopores and membranes technologies are a rapidly growing area of nanosciences with increasing applications in the fields of sustainable energy, environment, and nanobiotechnologies. The aim of the course is to provide the theoretical concepts governing the transport of fluids, ions and molecules in nanochannels and confined spaces.  It will highlight the new properties and functionnalities which arise from the interplay of surface interactions in solutions,  flow and transport.

 Content:
1. A general overview of nanopores and membrane technologies.
2. The basics of surface transport in fluids
     . Flow and diffusion at a nano-scale
     . Ions and molecule surface interactions in fluids
3. Coupled transport at surfaces and in nano-channels.
      Electro-osmosis, diffusio-osmosis and beyond
      Weak out-of-equilibrium limit and Onsager relations
      From nano properties to macroscopic efficiency
      Example of application: energy harvesting/conversion     
4. Non-linear and rectification effects.
     Nano-fluidic diodes, osmotic diode, and transistor.
5. Nano-pores for single molecules transport and detection
6. Membranes for fuel cells.

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Introduction to the statistical learning theory and prediction (regression/classification)

• Review of Models/Algorithms for supervised/unsupervised learning
• Illustration de ces algorithmes sur différents jeux de données on different dataset
  (intelligence artificielle, Bioinformatics, vision, etc ...)

Content:

• General introduction to the statistical learning theory and prediction (regression/classification)
• Generative approaches: Gaussian discriminant analysis, naïve Bayes hypothesis
• Discriminative approaches: logistic regression
• Prototype approaches: support vector machines (SVM)
• Unsupervised classification (kmeans and mixture model)
• Dictionnary learning / Sparse reconstruction
• Source separation

This course is given at Phelma-INP.

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The active material is made up of a large number of active living or artificial agents, each of which consumes energy to move and exert forces on other agents. The most important example is the plankton which represents the largest biomass on earth. Such systems are inherently out of thermodynamic equilibrium. The examples of active ingredient are very numerous and cover a wide range of length scales. At the nanoscale, important examples are biopolymers and microtubules in biology as well as synthetic janus nanoparticles and microparticles. On a larger scale, active systems are micro-organisms (plankton, bacteria), schools of fish, crowds of pedestrians and swarms of birds. Active matter is a relatively new material classification of soft matter: the most studied model, the Vicsek model, dates from 1995.

Active matter research includes hydrodynamics, kinetic theory and non-equilibrium statistical physics.

This course will present current research with illustrations at all the length scales mentioned above, emphasizing main relevant theoretical models. Within this course, a Python based programming for numerical and experimental study of active matter is proposed to the students at the LIPhy lab.


Content:

I. Microscopic phenomena:

• Self-propelled particles
• Biological and synthetic active particles
• Brownian motion
• Persistence Random walk.
• Interaction with environment (fluid/ particles/ walls)
• Dry active matter. Social interaction models: Vicsek model, Helbing model

II. Hydrodynamics

• Stokes equation
• Dipoles of forces and hydrodynamic interaction
• Pullers/pushers
• Interaction with a wall (Black green function)
• The squirmer model
• Singular solution of Stokes eq.

III. Macroscopic phenomena:

• Kinetic theory
• Rheology
• Bio-convection

IV. Python based programming for numerical and experimental study of active matter

V. Journal club:  Each student studies a published paper and presents it to the class.

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Introduction to biology (components and structure of the cells, genetic information, metabolism, regulation of gene expression), stochastic processes and diffusion in biological systems (with applications in population mobility patterns or in molecular motor processes), introduction to evolution (historical perspectives, the modern synthesis, genetic drifts), genetic circuits (transcription regulation, genetic logic gates, oscillatory or bistable circuits, synthetic biology), optimality in biological systems (evolution of genetic circuits, cost-benefit issues, game theory in evolving biological systems).

After each chapter, the newly introduced concepts will be illustrated through the analysis and discussion of scientific articles, either by the teacher or by the students. Each student will be required to present at least one article to the group during the overall lectures.

Introduction à la biologie (composants et structure des cellules, information génétique, métabolisme, régulation de l’expression génétique), processus stochastiques et diffusion dans les systèmes biologiques (applications à la mobilité des populations ou aux moteurs moléculaires), introduction à l’évolution (perspectives historiques, synthèse moderne, dérives génétique), circuits génétiques (régulation transcriptionnelle, portes logiques génétiques, circuits oscillateurs ou bistables, biologie synthétique), optimalité dans les systèmes biologiques (évolution des circuits génétiques, problèmes coût-bénéfice, théorie des jeux dans l’évolution des systèmes biologiques). 

Après chaque chapitre, les concepts nouvellement introduits seront illustrés à travers l’analyse et la discussion d’articles scientifiques, soit par l’enseignant soit par les étudiants. Chaque étudiant devra présenter au moins un article au groupe sur l’ensemble du cours.)

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Introduce the main analytical techniques to characterize molecular and biomolecular interactions, nanomaterials, surfaces and interfaces will be presented by the lecturers.

• Electronic microscopies
• Near field microscopies (AFM,STM,SNOM,…)
• Note that a more detailed approach of these techniques is available as an elective course.
• Surface analysis (XPS, AES, SIMS, EXAFS…)
• X-ray diffraction
• Large facilities (neutrons, ESRF)
• Optical techniques (ellipsometry, spectroscopies, SPR, OWLS,..)
• Nanogravimetry 

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Goal: Microfluidics studies the transport of liquids at the scale of some micrometer to the hundred of micrometer, such as the flow of red blood cells in a blood vessel, the transport of polymer chains in a porous medium, or the locomotion of micro-organisms. Nanofluidics studies the flow of liquids at the colloidal scale, that is at distance of the nanometer to the micrometer from a surface. This course introduces the concepts of low Reynolds number flows and surface-driven flows and describes the main properties of flows and transport at the sub-millimeter scale.

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From 2004, ESONN is a two-week course aimed at providing training for graduate students, postdoctoral and junior scientists from universities and laboratories, all around the world, in the field of Nanosciences and Nanotechnologies.    https://www.esonn.fr

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The Master's thesis project is a personal research work curried out during the second year of the master, to which the entire spring semester is devoted. For this purpose students perform an internship of minimum 5 months in a research team.  As a graduate student, you will be responsible for a specific project in nanosciences under the guidance of a thesis supervisor. You will have the opportunity to collaborate with PhD students, post-docs, full-position researchers and professors.

The master thesis is evaluated by a thesis manuscript and a public defense. In this manuscript the student is expected to:

• Provide a clear definition of the scientific or technological problem addressed
• Demonstrate mastery of the scientific literature related to the problem
• Describe the chosen approach to solve the problem, and present the results obtained
• Perform a scientific discussion of these results in relation to the state of the art

The public defense is held in front of a jury, which evaluates the completion of the above expectations through the student presentation and answers to questions. The defense also prepares students to the concourses held by the Grenoble's doctoral schools for the attribution of UGA funded PhD's positions.

According to the french law, the research institute will pay you a "gratification" of 530€/month during your research internship, for a maximum duration of 6 months in a given school year.

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