2nd year Nanobiosciences and nano-biotechnologies

Resp. : Prof. Hans Geiselmann and Prof. Didier Delabouglise

See here for the 1st year program of Nano-biosciences.

Taught courses include general biology courses mainly directed at students joining the program in the second year. It also includes a number of courses dealing with biosensors and micro-manufacturing (microfluidics, surface functionalization), techniques of broadband throughput screening and modeling and data analysis in Biology. These courses are also avalable to students in the Physics or Chemistry majors.

In addition to this, a long research internship in a laboratory is compulsory to complete the program.

Fall semester: 30 ECTS courses from september to january

Common program in nanosciences: 6 ECTS
                       Micro- Nanofabrication and cell-patterning lab  (3 ECTS)
                       Research Training (3 ETCS)

Core courses in Nanobiosciences: 9 ECTS
                       Characterization of (bio)molecular interactions ( 6 ECTS)
                       Biosensors & Micro-arrays (3 ECTS)

Broadening courses: 15 ECTS to be chosen in the list below or in the general list of broadening courses
                       Optics for biological systems (3 ECTS)
                       Microfluidics (3 ECTS)
                       Cell signaling (3 ECTS)
                       Physiology and Neurosciences (6 ECTS)
                       Surface functionnalization and electrochemistry (3 ECTS)
                       Biomaterials and biocompatible surface engineering (3 ECTS)
                       Nano-pores and membranes technologies (3 ECTS)
                       Molecular markers for medical imaging (3 ECTS)

Spring semester: 30 ECTS from february to june

General interest courses: 6 ETCS
            Foreign language (french for non-french speaking students):  3 ECTS
              3 ECTS among
                       Intellectual Property and Valorization  (3 ECTS)
                       Capita Selecta Lectures Series in Nanosciences (3 ECTS)
                       Other courses offered by the Service of Transverse Teachings (SET)

Master thesis: 24 ECTS.
Research project performed during a research internship of 5 months minimum.

 

Characterization of (bio)molecular interactions, nano-materials, surfaces and interfaces  6 ECTS
Contact:

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

Content:

  • 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

Prerequisites: Mécanique quantique, physique du solide, physique statistique. Electromagnétise, propagation d'ondes (guidées).

Biosensors and micro-arrays - 3 ECTS
Contact:   See also here

Goal: Specific measure of biomolecule concentration in fluids
Miniaturization of biological assays

Content:
Electrochemical biosensors
DNA microarrays
Protein microarrays
Lab on a chip
Fluorescence based detection
Electrical detection
Surface plasmon resonance and surface enhanced Raman scattering
Nanopores

Prerequisites: Molecular biology
Physico-chemistry of molecular interactions in solution
Basics of molecular spectroscopy

Microfluidics - 3 ECTS
Contact: Laurent DAVOUST  http://phelma.grenoble-inp.fr/studies/microfluidics-5pmbmfl5-616769.kjsp

Content:
Modeling and calculation of microflows
Digital/continuous microfluidics
Optimization tools for mixing at microscale
Tools for the prediction of chemical kinetics within bulk or at surfaces

Prerequisites: Continuum mechanics,  Laplace/Fourier transforms, Electrodynamics

Bibliography
•Low-Reynolds number hydrodynamics, Happel & Brenner, Martinus Nijhoff Publishers, 1983
• Intermolecular forces & surface forces, Israelachvili, Academic Press, 2nd Ed., 2000

Surface functionnalization and electrochemistry - 3 ECTS
Contact:   See also here

Goal: This course aims at giving a deep understanding of methods for modifying material surface properties for use in biotechnologies and micro-nanoelectronics. It contains basics on surface physico-chemistry, electrochemistry and chemical grafting.

Content:
Material interface
Basics on electrochemistry
Polymer adsorption
Langmuir-Blodgett layers, layer-by-layer assemblies
Chemical grafting on gold
Silanization
Radical grafting
Conductive polymers
Micro patterning

Prerequisites: Basics in chemistry

Optics for biological systems - 3 ECTS
Contact Martial BALLAND
Goal: Using a highly accessible style and format these lectures and labworks will provide an understanding of the underlying principles, benefits, and limitations of optical techniques currently used in biology.

Content: Without relying on complex mathematics we are going to address basic concepts in imaging such as contrasting techniques, fluorescence and also explores advanced techniques such as quantitative fluorescence, three-dimensional imaging, nonlinear microscopy. Of course we'll also have to spend some time on multiple appendices on cell handling, labeling, and image manipulation.

Prerequisites: basics of optics, molecular biology

Cell signaling (3 ECTS)
Contact: Franz BRUCKERT  See also here 

Goal: Using illustrative examples, lectures will explain the basics of inter- and
intracellular communication, the different techniques to study cell responses and the
complementarity between experimental approaches at different scales.

Content:
Signal transduction at the plasma membrane
Second messenger production
Regulation of protein activity by phosphorylation
Signal transduction to the nucleus and transcription regulation
Termination of cell responses
G-protein coupled receptors
Receptors with tyrosine kinase activity
Control of the eukaryotic cell cycle
Molecular basis of cancers

Prerequisites: Molecular and cellular biology
Bibliography
Stryer : Biochemistry, filth edt, Freeman
http://bcs.whfreeman.com/biochem5/
Alberts et al. Molecular biology of the cell fouth edt. Garland
http://www.ncbi.nlm.nih.gov/books

BIomaterials and biocompatible surface engineering - 3 ECTS
Contact:

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

Prerequisites: Surface chemical functionalization techniques

Nano-pores and membranes technologies - 3 ECTS
Contact:

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.

Prerequisites: Basics in thermodynamics, fluid dynamics, and semi-conductors.

Micro- nanofabrication and cell patterning lab- 3 ECTS
Contact: and

Goal: Introduce the students to the fabrication of micro- and nano-devices.

Content: The students follow a serie of lectures given by scientists expert in the field of nano-fabrication and nano-technology facilities in the Grenoble area. The topic of these lectures are
I. Engineering of surfaces
II. Micro and nanofabrication
III. Nanomaterials elaboration
IV. Surface functionnalization
V. Molecular recognition, vectorization, imaging :toward intelligent nanosystems -

Cell patterning lab :Constraining cell adhesion to micrometric adhesive islands separated by antiadhesive surfaces creates reproducible geometric cell shapes and controls cell physiology and ultrastructure (spreading, proliferation and programmed cell death, division).

Content: Practical will be organized as follows:
- Lithography of glass coverslips in clean room (0,5 day at CIME)
- Cell culture and preparation of the structured supports (one day at IAB)
- Cell staining observation and quantification under the microscope (one day at IAB)
Photolithography is used on functionalized glass covers to pattern arrays of either adhesive (fibronectin)and anti-adhesive areas. When the lateral distance between two consecutive 4x4μm islands is 4 μm, NIH 3T3 cells attached and spread on the array in a manner similar to that usually observed on uniformly coated surfaces However when we increased the distance between adhesive islands to 8, 12 or 16 μm, most of the cells adopted polygonal shapes which they attachedto the substratum solely by using adhesive spots at their corners.

Molecular markers for medical imaging - 3 ECTS
Contact:   See also here

Goal: Series of seminars on the development and use of contrast agents and molecular markers in biomedical imaging and therapy.

Content: Contrast agents and molecular markers for ultrasound, X-Ray and MRI imaging
Development and use of visible and infrared fluorophores
Application to cardiovascular diseases, cancer and neurodegenerative diseases.

Prerequisites: Molecular biology and physiology courses

Physiology and Neurosciences (6 ECTS)
Contact:       See also here

Goal: This course covers basics concepts in physiology from cardiac, respiratory and renal physiology to the knwoledge of some human pathologies. It introduces main conceps in neurosciences, from neuron to simple neural fonctions, and some neurodegenerative diseases. The course provides contacts with physicians and medical research.

Content :      Lectures on Physiology
         - Action potential and synaptic transmission
         - Molecular mechanisms of muscle contraction
         - Renal physiology: kidney organization, nephrons, excretion and dialysis, homeostasis, regulation of pH, blood pressure and blood volume by hormones, renal failure, hemodialysis, peritoneal dialysis
         - Cardiovascular physiology, physiology of respiration : gas exchanges, gas transport, cardiac output, regulation of heart rate, blood pressure, hemostasis, main cardiovascular diseases and respiratoiry diseases
         - Regulation of blood glucose concentration
Lectures in neurosciences
          - Location and functions of the nervous system
          - Basic principles of neurosciences : cells, electrical properties of cell membranes, cell excitability, membrane channels, action potential, synapses, neurotransmitters, other kinds of transmission
          - Main physiological consequences of neurotransmission : post-synaptic potentials, synaptic dendritic integration, neuronal phenotypes, groups of cells, importance of connectivity
          - Neural coding : example of the muscle spindle, generalization, population coding
          - Central pattern generators : basic principles, example of the respiratory centers
          - Plasticity : short-term and long-term synaptic plasticity, structural plasticity (axonal and dendritic modifications)

Prerequisites: Molecular biology course and cell signaling course