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