Y.

Coffinier (DR, CNRS)

Institut d’électronique, de microélectronique et de nanotechnologie (IEMN, UMR-8520),
Groupe des NanoBioInterfaces (NBI)

Yannick.coffinier@univ-lille.fr
 Few words on IEMN
Scientific activity divided in 20 research groups (~500 personnes) structured in 5 departments :
Half represent non-permanent people including :
160 phD students, 30 masters, Post-doc…

- Materials and Nanostructures

- Microtechnologies and microsystems (NBI)
- Micro, nano and opto electronics
- Telecommunication circuits and systems
- Acoustics

IEMN research activity is supported by huge technological means :

- Micro et nanofabrication cleanroom facilities ( 1700 m2)

- Characterization platform of electrical components and devices (MEMS) for large frequencies and temperature ranges.

- Near-field microscopy platform (AFM, STM, low temperature, ultravaccum…)

- Telecommunication platform

- Microfluidic/biology platform

2 Equipex :

Excelsior : Nanocharacterization platform : Near-field, IR, electrical….

Leaf : Flexible electronic – Laser ablation

Partner of Flagship graphene : fabrication, growth, electronic devices, sensors

Research activities of NBI

E. Coli
24H @ 30°C Growing
NB medium Petri dish- agar

• Nanomedecine :
SiNW SiNW-Ag SiNW-Cu -LNC for PDT – Cancer
• Environmental: -Composite materials (GO/Metal/Drug) :
- Energy harvesting theragnostic
- Remediation - photocatalysis -Drug release
-Bactericide surfaces/materials
-Antibiofouling surfaces

• Sensors:
- Biomarkers – Medical diagnosis • Biology :
- Pollutants & toxins -MEAs + optical + microfluidic plateform for
Tau agregats transmission study
-Identification of products (Alzheimer’s disease).
(synthesis)
- Organ on chip – Minibrain – Drug assessment

Schematic of a microsystem integrating microfluidics and MEA

03/31
 Outline

~30 hours of lecture

Including
Basic notions in micro-nanofabrication
Microfluidic (discrete microfluidic, superhydrophobic and
omniphobic surfaces and applications (µTAS))
Nanobiotechnologies
- Sensors, diagnosis, therapy…

Exams :
- 1 written exam (1h) – end/01/2022

- Oral presentation 10 min (group of 3@end of period) 01/13-14/2022

Project should concern Nanobiotech field :

Original device (medical, food, biology, cosmetic….)
Market and production part

Dead-line 11/10/2021 – Choice of your project and group composition

 Introduction to nanotechnology
Few definitions
Nanometer (nm)
From greek « nano » : tiny
For comparison a grain of rice compared to earth
Hair = 80000 nm of thickness
1nm : 10-9m = 10Å

Nanotechnologies are technologies recently developed by human for detecting, assembling,

transforming objects at the nanometer scale.
-Nanoparticles (NPs) : nanometric objets
Natural origin : dust from combustion (forest) or vulcano, sand, natural erosion of materials …
-Human can now make nanoparticles for using them in numerous applications

Nanosciences and nanotechnologies :

Same scale
Share and develop common tools
but with different purposes
- Nanotechnologies : concepts and « know-how» for making materials and systems with a specific
function for a specific application
- Nanoscience : study of new phenomena

-The classical laws of physic at the micro and macro scales are different at the nanoscale
Negligible effects at macroscale become important at the nanoscale (quantic effect, confinement
effect, van der vaals forces, aspect ratio, …)

New behavior = new science = nanosciences exploring these phenomena at the nanometer scale
Nobel price, 1965
Increase of the surface area by decreasing the size
Nanotechnologies in the world
Micro and Nano-fabrication techniques
Semiconductors

Direct bandgap Indirect bandgap

Case of Si
Nowaday big funderies (Intel, AMD, Samsung, STmicroelectronics…), arrived at technical
lock point : etching fineness ~7 nm
Number of transistors per processor
 New transistor architecture : 3D

- Ge instead of Si, or alloy Si-Ge….Cost?

 New record from MIT
september 2019

14000 transistors on 49mm2

10000 op/sec vs 109/sec (Si)

Each Transistor composed by ~100 CNT can be straight, twisted or entangled….

1 transistor made of 1 CNT

(Lab)
Far from that……
 STM in Biology

Enzyme + DNA
Matter manipulation
Local surface modification
To remember
 Top down and bottom-up approaches

It is often necessary to combine both approaches for making devices

 Bottom-up or Top-Down?

Other examples ?
 Lithography step (writting)

Latent image on substrate (surface) via resist

X times
Transfer of latent image to substrate

top-down Etching Material deposition Bottom-up

Dry CVD, Metallization, MBE, ALD….
Wet

Final device

Direct writting on surface (Maskless methods) = laser ablation, focused ion-beam

 Top-down approach

Silicon wafers

Lithography Latent image

Top-down or bottom-up Post-treatment – final product

Writting = lithography
• Spin-casting photoresist
• Polymer resin, sensitizer, carrier solvent
• Positive and negative photoresist

• Thickness depends on
• Concentration
• Viscosity
• Spin speed
• Spin time
Transfer to substrate
Lithography parameters are crucial!
Need to write several patterns on same surface from several masks
 Example of electronic mask

No need of several masks, several layers on same file

• Location of primary and secondary
flats shows
• Crystal orientation
• Doping, n- or p-type
 Etching : Transfer the latent image to the substrate

- Wet and dry etching processes

- Resist will protect the substrate underneath

Wet etching : first used in micro-nanofabrication

Selectivity > dry etching

Limited to object >3µm, low aspect ration object
Chemicals (selectivity, etch rate):
SiO2 (glass, silica) : HF, NH4F (etch rate : 1000A/min)
cSi : KOH, TMAH (Tetramethylammonium hydroxide), EDP (Ethylenediaminepyrocatechol)

2 types of etching : Anisotropic and isotropic

Etch rate function of crystalline orientation : [111], [110], [100]….

Isotropic vs Anisotropic Anisotropic

 • Etching of Si with KOH
Si + 2OH- → Si(OH)2 2+ + 4e-
4H2O + 4e- → 4(OH) - + 2H2

• Crystal orientation relative etch rates

• {110}:{100}:{111} = 600:400:1

• {111} plane has three backbonds below

the surface
• Energy explanation
• {111} may form protective oxide quickly

<100>
45° mirrors µfluidic channels for light sheet fluorescence microscopy
 Undercutting

• Convex corners
bounded by {111}
planes are
attacked
• Convex corners
bounded by {111}
planes are
attacked
Microneedles

Ken Wise group,

University of Michigan
Microneedles

Wise group,
University of Michigan
Microneedles

Ken Wise group,

University of Michigan
 E-Beam Lithography + Dry etching

Substractive process

NW based transistor
 Additive process

Patterns transferred by metallization

 MEMS actuators Pressure sensors

µturbine

William Blake's "Ancient of Days"

Gold nanopyramides
On silicon pedestals
Silicon-based transistor
Maskless methods
 Focus ion Beam (FIB)

Deposition etching
Deposition + selective etching Cutting for analysis
 Nanosphere Lithography + Dry etching

Nanosphere lithography (NSL)

Cheung et al., Nanotechnology 17 (2006) 1339–1343

All these SPM lithographies techniques are slows and not suitables for
replication and industrial applications…

Alternatives is to develop high-throughput massively parallel DPN.….

A) DPN patterning with 55,000 AFM cantilevers in parallel.
B) SEM image of a portion of an 88,000,000 gold dot array (40 × 40 within each block) on an
oxidized silicon substrate.
C) Optical micrograph of a representative region of the substrate where ~55,000
sophisticated features were patterned. Each of the circular features is a miniaturized
replica of the face of the 2005 US five cents coin. Scale Bars: 100 μm.
 X-Ray Lithography

Pros
• Shorter wavelength (0.4 – 4nm) than UV light
• High penetration, high resolution
• Minimum feature size around 10 – 20 nm
• Simple process – can use both positive and negative resists
• Essentially negligible diffraction
• Longer mask lifetime than with photolithography

Cons
• Very costly (compared to photolithography)
• Requires special masks and resists
X-ray absorbers: gold and tungsten
X-ray membrane: silicon carbide or diamond
• X-rays cannot be focused -> prevents the use of lenses
 Isolation of lymphocyte isolation based on ELISPOT technique
Examples antigen-specific antibody-secreting cells (ASCs

Rapid isolation of antigen-specific

antibody-secreting cells using a chip-
based immunospot array
Jin et al., Nature protocol, vol.6, 2011
 Rapid isolation of antigen-specific
antibody-secreting cells using a chip-
based immunospot array
Jin et al., Nature protocol, vol.6, 2011
 Cell micropatterning

(A) The device was assembled by gluing the PET

polymer mask to a glass slide and overlaying
a silicon gasket and slide module.
(B) The wells of the slide module were then
filled with mixed PDMS and cured overnight
to yield stamps.
(C) Next, stamps were inked with protein
solution, before printing the protein onto a
glass slide.
(D) Once the protein was patterned onto the
glass slide, the surrounding substrate was
made non-permissive for cellular attachment
and growth by coating with a PLL-g-PEG
solution.
(E) Astrocytes were grown on the substrate for 2
DIV before (F) seeding hippocampal neurons
and growing them for 5–13 DIV. The
technique yields cocultures of hippocampal
neurons growing on isolated astroctye
microislands.

Generation of microisland
cultures using microcontact
printing to pattern protein
substrates . Ricoult et al.,
Journal of Neuroscience
Methods, vol. 208, 2012
 Voltage controlled nano-injection system
Cell surgery for single-cell surgery.
Seger et al., Nanoscale, 2012

The entire protocol requires on average less than 1 minute per cell, and up to 10
cells can be injected in less than 5 minutes .
Multicomponent injection into human fibroblast cells.
(A) False color image of cells injected with a double-barrel nanopipette containing CFSE (green) and SR (red) in separate
barrels (20 V, 500 ms each).
(B) False color image of multicomponent injection with different dye ratios.
A bias of 20 V was applied to each barrel for a fixed time to selectively inject one dye at a time. Left, yellow/orange
color: 1000 ms applied to SR channel followed by 400 ms to CFSE channel. Right, green/yellow color: 400 ms applied to
SR channel followed by 1000 ms to CFSE channel.