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COMUNICAÇÃO TÉCNICA ______________________________________________________________________________________________________________________________________________________________________________________________________
Nº 172232
Bionanomanufacturing: IPT’s strategy and the EMBRAPII Program
Slides da apresentação no Symposium on Nanotechnology and its Application in Health, 2013, Belo Horizonte.
A série “Comunicação Técnica” compreende trabalhos elaborados por técnicos do IPT, apresentados em eventos, publicados em revistas especializadas ou quando seu conteúdo apresentar relevância pública. ___________________________________________________________________________________________________
Instituto de Pesquisas Tecnológicas do Estado de São Paulo S/A - IPT
Av. Prof. Almeida Prado, 532 | Cidade Universitária ou Caixa Postal 0141 | CEP 01064-970
São Paulo | SP | Brasil | CEP 05508-901 Tel 11 3767 4374/4000 | Fax 11 3767-4099
www.ipt.br
BioNanoManufacturing: IPT’s Strategy and the EMBRAPII Program
SYMPOSIUM ON NANOTECHNOLOGY AND ITS APPLICATIONS IN HEALTH
November 2013
Dr. Kleber Lanigra GuimarãesMaterials Engineer
kleberlg@ipt.br
One of the first applied R&D institutions inBrazil and the largest in the Latin America.
A public company linked to the Governmentof the State of São Paulo through theSecretariat for Economic Development,Science and Technology.
The IPT
The beginning
1899
SpinoffMaterials Resistance Laboratory of the University of São Paulo - USP
1934: IPT is established as a
independent unit
1960s: technical areas are
restructured Creation of technical divisions focusing on
engineering areas
1970s: improves its relationship
with industries Efforts to increase R&D contracts with
private companies
1975: creation of the
Government Secretariat and link
of the IPT
2005: technical areas are
restructured Efforts to focus on client needs
2008/2013: Modernization of IPT
History
Infrastructure IPT units in:
São Paulo
Franca
(individual protection equipment))
São José dos Campos*
(composite materials)
14 technology centers
40 laboratories
103.523 m2 of labs area
240.000 m2 of total area
* in progress
Markets
Transport Infrastructure
Naval
Pipeline
Railroad
Airspace
Cargo
Roads
IT & ITS
• Metallurgy
• Textiles, leather &
wood
• Plastics, rubber &
composites
• Pharmaceuticals
• Cosmetics
• Bioproducts
SMEs
Technological Support to SMEs (production, quality and exports)
Energy Materials and Chemistry
Civil works
Buildings
Environmental impacts
Mining
Tests, calibrations, analysis and special tests
Metrology
Oil and gas
Ethanol
Biomass
Technical Centers
CT-Obras
Center for
Infrastructure Work
Technology
CTMM
Center for Technology
in Metallurgy and
Materials
CTGeo
Center for
Geoenvironmental
Technologies
CT-Floresta
Center for Forest
Resource Technology
CNaval
Center for Maritine
and Offshore
Engineering
CMF
Center for Fluid
Metrology
CETIM
Center for Technical
Textiles and Manufactured
Products
CIAM
Center for Information
Technology, Automation
and Mobility
CINTEQ
Center for the Integrity of
Structures and
Equipment
CETAC
Center for the Built
Environment
CMQ
Center for
Metrology in
Chemistry
CME
Center for
Mechanical and
Electrical Metrology
NT – MPE
Technological Support
to Medium and to
Small Enterprises
NT- Bionanomanufacturing
Bionanomanufacturing
Renewable Energy
Renewable Energy
Energy – Oil & Gas
Transportation
Chemistry and Materials
Chemistry and Materials
Infrastructure
Technical activities 2012
R&D projects21% of the total budget
Technological services29% of the total budget
Metrological development
& calibration49% of the total budget
Information & Education1% of the total budget
2012 figures
59%
R&D contracts
and services
41%
State of
São Paulo
Government
Technical production: indicators
� Over 3000 clients
� Technical reports & certificates : 26,828
� Publications: 200 scientific & technical papers
� R&D projects: 107
� Patents: 8
Annual budget: R$ 137 million
Personnel in December 2012
Researchers 356
Technitians 215
Adm. Suport 235
Interns 102
Total 908
The BioNanoManufaturing Unit
• Installation• Approx.. 8.000 square meters in
three floors • Clean rooms (classes 100, 1K and
10K) and labs environmentally protected for vegetal & animal cells
• Office space for 65 permanent & guest researchers
• Auditorium & facilities for events (up to 125 attendees)
• Up to 1.000 meters for pilot plants & expansion
• Permanent staff• 4 Administrative & management• 26 researchers• 13 Technicians
• Investment (Modernization)• R$ 26 million installation• R$ 30 million new
technologies & processes
Terminology
Bio Nano Manufacturing
MicroManufacturing and
Three-dimensional high performance metrology
Wet-Chemical methods for synthesizing and
functionalizing nanoparticles
Industrial Biotechnology - BioProcesses
The Goal of BioNanoManufacturingAn important goal of bionanomanufacturing is to create functional
devices that incorporate biological and nonbiological building blocks
using either parallel or serial nanofabrication techniques.
Bottom-Up Nanofabrication Approaches Top-Down Nanofabrication Approaches
Self-Assembling AFM probe
CHOW et al., Bionanomanufacturing: Processes for the manipulation and deposition of single molecules
Mixers Valves
Flow Sensors
Drop Generators
Coolers
Micro Devices
Microdevices for bio & nano applications
Biochips
The Impact of BioNanoManufacturing
Nanostructured materials often exhibit unique chemical, mechanical,
electrical, magnetic, thermal, and optical properties that are dramatically
different from those of their bulk counterparts
Miniaturization of diagnostic, therapeutic, and surgical devices allows
mass production of low-cost, portable, modular biomedical devices with
improved sensitivity, speed, and precision
Serial assembly of biological components with predefined functions
enables the fabrication of sophisticated, self-sufficient and adaptive
systems
Biological materials and systems are often governed by nanoscale
properties and processes, which provide a new set of tools and building
blocks for bionanomanufacturing.
Background
Previous experience:• Biotechnological &
chemical processes,
including microfluidic
applications & macro-
measurements
Modernization of
original capability:• Nano scale in chemicals &
materials
• New lab. capabilities &
environments
• Improved technologies for
characterization
• Micro-fabrication &
evaluation beyond
microfluidic devices
Technological platforms
Nanotechnology: expertise related to particle technology with special
emphasis on controlled release applications (encapsulation technologies)
Biotechnology: less aggressive processes to the environment with lower
energy consumption and using renewable raw materials
Microtechnology: manufacturing capability of micro & nano devices for
production of biosensors, microreactors, MEMS and NEMS devices
High performance metrology: 3D measurement capability for diagnostic
and design feedback of micro and nano devices
Bio
Na
no
Ma
nu
fact
uri
ng
• Main focus
• Development of processes for production of bioactive cells, focusing
on the substitution of chemical processes.
• Development of bioprocesses through selection of micro organisms,
genetics, purification, bio-characterization and process scale-up
• Technological solutions
• Selection and genetic improvement of micro-organisms
• Development, optimization and scale-up of bio-processes
• Purification and characterization of bio-molecules
• In-vitro evaluation of antimicrobial activity and cytotoxicity
• Evaluation of biodegradability
• Metabolomics
• Infrastructure (highlights)
• Automated bio-reactor (from 0.7 to 100 liters)
• Mass chromatography
• Screening of micro-organisms and cells culture infrastructure
• High precision optic and electronic microscopes
• Micro-organisms manipulation class 1 and 2
• O2/CO2 Gas analyzers (respirometers)
Biotechnology
Process Development & Optimization
• Main focus
• Development of nanostructured systems using polymerization,
emulsification, solvent evaporation, spray-dryer and microfluidic
processes.
• Technological solutions
• Nano-particle synthesis
• Polymeric nano-fiber production through electrospinning
• Nanomaterial functionalization
• Surface functionalization & modification
• Design of controlled delivery systems
• Development of complex fluids
• Characterization techniques for nanomaterials and complex fluids
• Infrastructure (highlights)
• Automated reactors
• High-pressure homogenization processes
• Nano spray-dryer
• High precision microscopes
• High performance particle analyzers
• Characterization capabilities: physical, chemical, surfaces &
performance
Nanotechnology
Hybrid organic-inorganic nanoparticles
One-step pickering emulsion polymerization route
Chemical Protection Agent
(Molecular Absorber)
Physical Protection Agent
(Nanoparticles)
Polymer Matrix
Ceramic Oxide
Active Ingredient
UVA / UVB protection
Functional Coatings
• Main focus
• Design, manufacturing and characterization of microsystems such as
MEMS and biosensors.
• Development of clean-room processes for multi-layer materials.
• Technological solutions
• LTCC- Low temperature co-fired ceramic microsystems
• Micro-devices on silicon, glass, polymeric materials and metallic
substrates
• Surface functionalization and characterization
• Infrastructure (highlights)
• LTCC prototyping capability including micro-milling, serigraphy,
lamination, sintering and assembly
• Thin & tick film deposition also for polymeric films
• Humid and plasma corrosion
• Photolithography
• Assembly and wire-bonding
• Surface measurement and characterization
• Micro-drillings and laser manufacturing
• Packaging and device testing
Microtechnology
• Main focus
• Dimensional and geometrical evaluation of micro and nano devices.
Qualified information for design feedback and quality improvement.
• Technological solutions
• Dimensional and geometrical metrology capability for regular and free-
form geometries evaluation, including tolerancing
• Non-destructive measurement of internal features in steel, alloys,
magnesium, titanium, ceramic and polymers
• Internal defects detection, e.g. porous and physical contaminants
• Sub-micron measurements, calibrations and traceability
• Data analysis and digitalization capability for reverse engineering
• Infrastructure (highlights)
• 3D Metrotomography
• 3D Coordinate multi-sensor metrology (contact, non-contact)
• Data fitting capability in high-density 3D data (VG-StudioMax™ &
SmartFit™)
• Geometrical, Dimensioning and Tolerance Analysis – GD&T
(SmartProfile™)
• Reverse Engineering (Geomatic™)
High performance metrology
Actual R&D Projects...
Microfluidic techniques for synthesizing particles
LTCC
Technology
ABATE et al., Microfluidics techniques forsynthesizing particles
Journal of Nanomedicine & Nanotechnology (2013)Schianti et al.
Progress in Nanotechnology and Nanomaterials (2013)Schianti et al.
Proposed solutionOil and gas industry needs fast diagnostics of bacteria that causes corrosion
Biosensors for corrosion detection
Future Trends...
The Embrapii in Brazil
Embrapii: Brazilian Enterprise for Innovation in Industry
Concept: Government action towards the intensification of innovation processes
& results in Industry.
Focus: R&D projects in cooperation with Industry to speed up pre-competitive &
innovative processes and products development.
Strategy: co-funding of applied research projects using the available Brazilian
Institutes of Research (⅓ + ⅓ + ⅓)
Action deadlines (pilot phase)
Contracts: 24 months, up to December 2013 (extended until July 2014)
Projects conclusion: 48 months, up to December 2015 (extended until July 2016)
Invited R&D Institutes (Pilot phase)
Energy & Health
Automation & Manufacturing
BioNanoManufacturing & new ceramic, metallic and polymeric materials
Obrigado !
Thank you!
Further details at:
www.ipt.br
www.ipt.br/bionanomanufatura
Contact:
bionano@ipt.br
Micro-Nano measurement & diagnostics
ESEM-FEG-FIBHigh Resolution Microscopy
ComputerTomography
MultisensorMetrology
Production of Biopolymers
Microbiology and Molecular Biology
Experiments in bioreactors (15L)
Modeling, simulation and Process Optimization
Different products in pilot scale (100L)
Strain selection
0
0,5
1
1,5
2
2,5
19931995
19961998
2000
Shaker
Bioreactor
Mutant Bac.
Bioreactor
Fed-Batch
Bioreactor
High Density
Process
Mathematical
Optimization
Technology Evolution - IPT - Polyhydroxyalkanoates
PHA Productivity (g/L∙h) - Bacteria (inverted sucrose)
Ex: Production development of Biodegradable Polymer - PHB
Production of active agents using biotechnology
Ex. antimicrobials can be applied as natural preservatives to replace chemical preservatives.
Scaling-up of experimental conditions
• Investigation of optimum culture conditions
• Development of bioreactors processes using renewable raw materials
Purification and characterization
Prospection of microorganisms
Controlled release of active agents
Encapsulation Technologies
Textiles impregnated with particles containing an encapsulated active ingredient
Mechanisms for controlled release
Micro(nano)spheres Micro(nano)capsules
Time
Stimuliresponsive
Bioreactor for semi solid cultivation
60,4%92,7%
0
50
100
150
200
250
300
350
400
0 20 70
Co
nce
ntr
ati
on
of
HC
H
(mg
/Kg
)
Time (days)
Microbial reduction of HCH
Bioremediation of contaminated areas
Ex: Study of Bioremediation Technology for soil contaminated with HCH
Sol-gel based Inorganic Coatings
HydrolisisPolymerization
Sol-Gel Technology
Metal AlkoxideSolution
Sol
Substrate SubstrateHeat
Xerogel film Dense filmCoating
TiO2-based Superhydrophilic Photocatalytic Coating
Phase Change Materials
3D Distribution
Virtual 2D Distribution
Temperature Cycle
Composites
Working Principle
Functional Coatings
Emulsion polymerization route
Biodegradation assays
Tests of biodegradability
Methodology: IBAMA and OECD 301-B (1992) - Immediate biodegradability of water soluble or poorly water soluble nonvolatile organic substances.
% CO2
0,010,020,030,040,050,060,070,080,090,0
100,0
0 100 200 300 400 500 600 700 800 900 1000 1100 1200
Tempo ( h )
% C
O2
PADRÃOAMOSTRAINIBIÇÃO
Future: Aerobic biodegradability of plastic: Brazilian Association of Technical Standards NBR 15448-1 and 15448-2
Biorefinary: Renewable sources of raw material
Agro-industrialresidues
Sugar cane bagasse pretreated by steam
explosion
Enzimatic hydrolysis
Enzymatic hydrolysis of sugar cane bagasse
Isolation of microorganisms
Biopolymer from residual glycerol (biodiesel synthesis)
Bioprocess development
P-1 / FR-101
Fermentation
198.00 m3 CT = 49.50 h
P-2 / V-101
Storage
165.00 m3 CT = 1.00 h
Glicerol + água160.00 ton/batch
CO2 (saída do reator)
Biomassa + água3.10 ton/batch
S-103
P-3 / DS-101
Centrifugation
148.50 m3/h CT = 1.00 h
S-105
S-106
P-5 / MX-101
Mixing
26.93 MT/h CT = 1.00 h
S-109
P-6 / DS-102
Centrifugation
26.83 m3/h CT = 1.00 h
S-110
S-111
P-8 / DS-103
Centrifugation
8.75 m3/h CT = 1.00 h
P-9 / SDR-101
Spray Drying
1.00 m3 CT = 1.00 h S-116
S-118S-115
S-119
P-4 / V-102
Blending / Storage
28.68 m3 CT = 1.00 h
S-102
S-101
S-104
P-7 / V-103
Blending / Storage
9.73 m3 CT = 1.00 h
S-107
S-108
S-112PHB
7692.16 kg/batch
Active Pharmaceutical
Ingredient (API)
Solubilization Nanoparticle
Formation
Increased bio-availability
of poorly soluble drugs
Microfluidics applied to particle production
CrystalsMicrofluidic device
Characterization
Amorphous
Nanoparticles
ϕϕϕϕ ≈ 200 nm
Antibacterial polymer coating
Hydrophilic polymeric coating
NanoSilver (NanoAg)
Silver Ions (Ag+)
Bacteria (live)
Bacteria (dead)Substrate
Wet Chemical Synthesis of Nanoparticles
Dip-Coating Process
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