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Nanotech applications in
Bioengineering
• Giampaolo Mistura
• Laboratorio di Fisica delle Superfici e delle Interfacce
• Dipartimento di Fisica G.Galilei, Università di Padova
Università di Padova
Founded in 1222. Galileo Galilei taught at Padova between 1592 and 1604. Currently there are about 60,000 students
Physics department: more than 80 faculty members
Anatomical theatre, 1594
Cattedra di Galileo
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Outline
•Introduction
•DNA detection in nanopores
•Nanoparticles
•Biomimetism
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
•Electroporation
Biological engineering or bioengineering is the application of concepts and methods of engineering (derived from physics,
chemistry, mathematics, computer science…) to (human) biology and medicine
Biomedical devices and sensors Biomedical imaging Medical therapy
Tissue engineering Synthethic biology
…
Biomimetism
Bioengineering
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
•Nanoparticles
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Nanoparticles
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
A nanoparticle is considered a particle having a size 10-100 nm. It is much smaller than a typical cell (~µm) and comparable with the
size of proteins. Potentially, it is the ideal probe-tool to access the biological material
at the subcellular level.
Applications of nanoparticles in biomedicine:
• Fluorescent labelling • Protein detection
• Probing of DNA structure • MRI contrast enhancement
• … • Cancer treatment • Drug delivery
• Tissue engineering • …
Bio-nanoparticles
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
To be used as bio probes-tools nanoparticles are multilayered objects having many degrees of complexity
Physical level: Core Properties: size, shape (spherical, disk, tubular), material (metallic,
magnetic, polymeric, inorganic) Biochemical level: Outer functional layers
Functions: protection, biocompatibility, recognition, detection, signalling
Targeted nanoparticle BIND-014
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Core: polymeric biodegradable material containing the chemo drug Outer coating: i) targeting molecules that recognize the protein PSMA (prostate-specific membrane antigen), found abundantly on the surface
of most prostate tumor cells as well as many other types of tumors ii) polyethylene glycol molecules, which keep the nanoparticles from being
rapidly destroyed by macrophages
Langer et al, PNAS 2012 BIND Biosciences
•DNA detection in a nanopore
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Coulter counter
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
It is an apparatus for counting and sizing particles (cells, bacteria, virus…) suspended in electrolytes.
It consists of one or more microchannels that separate two chambers containing electrolyte solutions. As fluid containing particles or cells is drawn through each microchannel, each particle causes a brief change to the electrical resistance of the liquid. The counter detects these
changes in electrical resistance
Nanopore in a polymeric chip
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Fluidic chip made in PDMS
Fanzio et al, Lab Chip 2011
Fabrication chip
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Fluidic chip made in polydimethylsiloxane (PDMS)
Fanzio et al, Lab Chip 2011
Advantages PDMS
• Elastomeric
• Low viscosity
• Low surface energy
Easy and faithful casting
• Optical transparency
• Air permeable
• Biocompatibility
• Low cost
Nanopore as a DNA detector
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Solution containing DNA, 48.5 kbp
Fanzio et al, Lab Chip 2011
•Electroporation
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Electroporation
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Electroporation is a physical method to increase the electrical conductivity and permeability of the cell membrane by the application of an external electric field. It is usually used in molecular biology to introduce substances into the cell, such as a molecular probe, a drug
that can change the cell's function, a piece of DNA…
Electroporation in a polymeric chip
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Fluidic chip made in PDMS
Chiara Nardin, Tesi UniPD, 2013
Electroporation tests
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Electroporation of CHO-K1 cells
Chiara Nardin, Tesi UniPD, 2013
•Biomimetism
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Lotus leaves
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Lotus effect
Lotus leaves are self-cleaning
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
QUESTION What are the essential
parameters behind this effect?
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Which surface is more hydrophobic?
From a static point of view, the larger the contact angle Θ, the more hydrophobic the surface is.
However, for applications the dynamic response is what matters. In this case, the hysteresis ΔΘ = Θadv – Θrec is the key parameter
Oner and McCarthy, Langmuir 2000
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Lotus leaves
Lotus effect is the result of -very low contact angle hysteresis thanks to a rough (at multiple length scales),
hydrophobic (wax) surface which i)favors the entrapment of air underneath the drop
(i.e. fakir drop or drop lying on an air cushion) ii) makes the contact line very tortuous and less stable
-low adhesion of dust particles to a rough surface
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Nanoimprinting of superhydrophobic surfaces
A. Pozzato et al Microelectron. Eng., 2006,
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Nanocasting of artificial Lotus leaves
M. Sun et al Langmuir, 2005,
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Hairy surfaces
S. Varagnolo et al, in preparation
Produced by nanocasting of PDMS in porous alumina matrices. PDMS hairs have height of ~200 nm and size of ~30 nm
Gecko
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Prof. Kellar Autumn, Lewis and Clark College
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Geim et al, Nature Mater. 2003
Artificial Gecko feet
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Gravitational force acts between any two
masses (classical)
𝐹𝐺 = 𝐺
𝑚1𝑚2
𝑟2
Van der Waals forces
Van der Waals force acts between any two
instantaneous electric dipoles (quantum)
𝐹𝑉𝑑𝑊~ −1
𝑟7
Electrical force acts between any two
charges (classical)
𝐹𝐸 = 𝐾
𝑞1𝑞2
𝑟2
Sufficiently close to a surface, any object experiences an attractive
Van der Waals force which decays as 1/r4
Sufficiently close means within about a micron
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Similar to the natural gecko setal array, the microfiber array is a shear-controlled smart adhesive. Contact area increases with increased shear load and virtually disappears when shear load is removed, allowing
for controlled attachment and detachment.
Dry (Gecko) adhesives
Prof. Ronald Fearing, UC Berkeley
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
Smart Gecko tape
Prof. Ronald Fearing, UC Berkeley
CONCLUSIONS
•Advances in bioengineering exploit nanotechnology for the realization of smart materials (including pharmaceuticals) and of powerful
diagnostic tools
•A key feature of all modern R&D, both at the industrial and university level, is its high interdisciplinarity
MESCOLARSI/CONTAMINARSI FA BENE!!!!
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013
ACKNOWLEDGMENTS
Matteo Pierno Evandro Piccin
D. Ferraro S. Varagnolo V. Schiocchet E. Chiarello D. Quagliati
Paolo Sartori, Paolo Fantinel, Nicola Galvanetto, Valdo Chilese, Carlo Rigoni
http://lafsi.fisica.unipd.it/ Convergenze Parallele, Ecotekne,
Lecce, 10-11/10/2013
SPECIAL THANKS
Mauro Sbragaglia, G Amati and Luca Biferale
Dipartimento di Fisica, Università di Tor Vergata, Roma
Ciro Semprebon, Martin Brinkmann
MPI for Dynamics and Self-Organization, Goettingen
2011 ERC Grant DroEmu and PRAT2012 MiNet, Padua University
Convergenze Parallele, Ecotekne, Lecce, 10-11/10/2013