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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


•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


•Nanoparticles


Nanoparticles


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


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

http://www.jnanobiotechnology.com/content/2/1/3/figure/F1?highres=y

Targeted nanoparticle BIND-014


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


Coulter counter


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


Fluidic chip made in PDMS

Fanzio et al, Lab Chip 2011

Fabrication chip


Fluidic chip made in polydimethylsiloxane (PDMS)


Advantages PDMS

• Elastomeric

• Low viscosity

• Low surface energy

Easy and faithful casting

• Optical transparency

• Air permeable

• Biocompatibility

• Low cost

Nanopore as a DNA detector


Solution containing DNA, 48.5 kbp


•Electroporation


//upload.wikimedia.org/wikipedia/commons/c/cc/Pore_schematic.svg

Electroporation


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…

http://en.wikipedia.org/wiki/File:Electroporation_Cuvettes.jpg

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=edGsBN8MyUjCkM&tbnid=AzDi5uj9OKswgM:&ved=0CAUQjRw&url=http://www.bio-rad.com/en-us/applications-technologies/instrument-based-transfection-methods&ei=h2NUUsXvFunV0QXJqIDgBg&bvm=bv.53760139,d.bGE&psig=AFQjCNEZGvPADgPP5CndiXjAm4UF_CeJ-g&ust=1381348603584126

Electroporation in a polymeric chip


Fluidic chip made in PDMS

Chiara Nardin, Tesi UniPD, 2013

Electroporation tests


Electroporation of CHO-K1 cells

Chiara Nardin, Tesi UniPD, 2013

•Biomimetism


Lotus leaves


Lotus effect

Lotus leaves are self-cleaning


QUESTION What are the essential

parameters behind this effect?


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


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


Nanoimprinting of superhydrophobic surfaces

A. Pozzato et al Microelectron. Eng., 2006,


Nanocasting of artificial Lotus leaves

M. Sun et al Langmuir, 2005,


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


Prof. Kellar Autumn, Lewis and Clark College


Geim et al, Nature Mater. 2003

Artificial Gecko feet


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


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


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!!!!


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


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