COMUNICAÇÃO TÉCNICA - escriba.ipt.brescriba.ipt.br/pdf/172088.pdf · A série Comunicação...
Transcript of COMUNICAÇÃO TÉCNICA - escriba.ipt.brescriba.ipt.br/pdf/172088.pdf · A série Comunicação...
COMUNICAÇÃO TÉCNICA ______________________________________________________________________________________________________________________________________________________________________________________________________
Nº 172088
Microfluidic devices applications to microencapsulation
Mário Ricardo Gongora-Rubio
SEMINARY: MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS, 2013, Campinas. Palestra apresentada no ITAL
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
SEMINARY: MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROFLUIDIC DEVICES APPLICATIONS TO
MICROENCAPSULATION Mário Ricardo Gongora-Rubio – [email protected]
Institute for Technological Research (IPT)
Bionanomanufacturing Center Microtechnology Laboratory
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
SUMMARY
Introduction
MicroTechnology
Fabrication of MicroFluidic Devices
Chemical Process Intensification
Microfluidics
Microencapsulation
Microfluidic Devices in Microencapsulation
Conclusion
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
INTRODUCTION
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
IPT
Institute for Technological Research of the State of São Paulo S.A. One of the first applied R&D&I institutions in Brazil and one of the largest applied multipurpose R&D&I institutions in Latin America Linked to the Secretariat of Development of the State of São Paulo IPT provides technological solutions to public and private companies and institutions
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
THE BIONANOMANUFATURING CENTER
• Installation • Aprox. 8000 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 1000 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
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
TECHNOLOGICAL PLATFORMS
Nanotechnology: new possibilities of process intensification (physical,
chemical & biological) through scale reduction with gains in product quality
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
N
an
o
Ma
nu
factu
rin
g
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROTECHNOLOGY
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROTECHNOLOGY
Is an outstanding strategy for miniaturization and integration where the same principles as in microelectronics, are applied to Mechanical, Acoustic, Optical, Magnetic, Thermal, Chemical or Biotechnical components and systems.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
• 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 AT IPT
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROFABRICATION EQUIPMENT AT IPT
Deposition – PVD (Sputtering and Evaporation) e PECVD for silicon oxide & Nitrates, Thick film deposition & dispensing, Parylene biocompatible films, electrochemical deposition.
Photolitography –Mask direct write , mask Aligner, spin coater, developer and baker photoresist processing.
Corrosion & Cleaning - DRIE-ICP Plasma corrosion, Plasma Dry cleaning and surface activation, Wet corrosion and cleaning.
Micromachining - Laser UV (355 nm), 5 axes CNC with 0,1 µm resolution, LTCC laser Micromachining. Packaging – Fluid dispensing, Re-work system, Wafer bonding system, Wire bonding, Chip to Chip bonding workstation. Caracterization – SEM, Profilometers (1 for Thin Films + 1 for Thick Films), equipment for dimensional & geometrical measurements.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROSYSTEM PLATFORMS
Parameter ICs MEMS TAS MECS
Function Signal
processing
Signal
acquisition &
Control
‘Lab on chip’ Process
intensification
Primary
Materials
Semiconductors Silicon,
Ceramics, glass
& polymers
Silicon,
Ceramics, glass
& polymers
Metals, Silicon,
LTCC Ceramics,
Glass & polymers
Key Element Transistors Transducers &
actuators
Microfluidic
pumps and
valves
Microchannel
arrays
Characteristic
Feature Size
100 nm µm tens of µm 1 to 500 µm
System Size mm to cm mm to cm mm to cm mm to meters
IPT Research on
Microprocess Engineeering
FABRICATION OF
MICROFLUIDIC DEVICES
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
1. A system of channels is designed in a CAD program.
2. A commercial printer uses the CAD file to produce a high-resolution transparency
3. This transparency is used as a photomask in contact photolithography to produce a master.
4. A master consists of a positive relief of photoresist on a silicon wafer and serves as a mold for PDMS.
5. Liquid PDMS pre-polymer is poured over the master and cured for 1 h at 60 °C.
6. The PDMS replica is peeled from the master
7. The replica is sealed to a flat surface to enclose the channels.
PDMS RAPID PROTOTYPING
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
Glass Microfluidic Devices
1. Glass substrate cleaning
2. Chrome film deposition and oxidation
3. Photoresist deposition and Photolithography
4. Glass etching to obtain microchannels
5. Bonding of upper glass substrate
(a)
(b)
(c)
(d)
(e)
Processo de fabricação de microcanais em vidro: (a) limpeza do vidro, (b) deposição do filme de cromo e oxidação, (c) deposição do fotoresiste e fotolitografia, (d) vidro preparado para corrosão, (e) vidro com os microcanais.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
FABRICATED MICROFLUIDIC DEVICE
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
What is LTCC ?
• LTCC was originally developed by Hughes and DuPont for Military Systems, using Glass-Ceramic Composite Materials.
• The (LTCC) technology can be defined as a way to produce multilayer circuits with the help of single tapes, which are to be used to apply conductive, dielectric and / or resistive pastes on.
• These single sheets have to be laminated together and fired in one step all.
Multi Chip
Module Bluetooth Interface (National)
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
FABRICATION OF MICROFLUIDIC DEVICES IN LTCC
Micromaching (Laser)
Screen Printing (Thick Film material
deposition)
Lamination (Press)
Sintering (Furnace)
Singulation
IPT Research on
Microprocess Engineeering
CHEMICAL PROCESS INTENSIFICATION
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
PROCESS INTENSIFICATION THROUGHT MINIATURIZED CHEMICAL PROCESSES
Miniature reaction and other unit operations,
Have advantages over conventional chemical systems
Yesterday Today Tomorrow (Today in Merck)
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
PROCESS INTENSIFICATION ADVANTAGES
1. Novel or Enhanced Products
2. Improved Chemistry
3. Enhanced Safety
4. Improved Processing
5. Energy and Environmental Benefits
6. Sustainable Technologies
7. Capital Cost Reduction
8. Low Inventory Advantage
9. Enhanced Corporate Image
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
CONTINUOUS MICROFLUIDIC REACTORS
Functional characteristics of microfluidic continuous reactors relative to conventional batch reactors comprise:
A high surface area to volume ratio;
Diffusion dominated mass transfer in laminar flow;
Intensified surface effects involving rapid heat and mass transfer;
Spatial and temporal control of reagents and products;
Scaling readiness (numbering-up)
The possibility to integrate processes and instrumentation systems on a single technology platform leading to the concept of the FAB ON A CHIP.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
LESS ENERGY CONSUMPTION
Micromixers consume less energy for stable emulsion production compared to conventional stirrers
Source: Bayer
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROFLUIDIC APPLICATIONS
Fluid Management Systems
Micro Analytical Systems
Micro Reaction Systems
Micro Heat Exchange Systems
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MINIATURIZED CHEMICAL PROCESS SCALE-OUT
Scale-Up Scale-out
NUMBERING-UP NEW DESIGN
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
SCALE-OUT OF MICROREACTORS
There are two ways to scale-out microreactors: internal numbering-up (the main functional element of the experimental set-up is numbered up) and external numbering-up (the whole laboratory set-up is reproduced)
INTERNAL NUMBERING-UP EXTERNAL NUMBERING-UP
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROFLUIDICS
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROFLUIDICS
Behavior of fluids in Micro scale: Control of small fluid volumes,
Low Reynold’s number → laminar flow,
Viscous forces overwhelm inertial forces,
Fast response time,
Reaction condition well controlled,
Low energy consumption,
Small systems size,
Continuous processes
Low raw materials waste
Microfluidics —the science of designing, manufacturing, and
operating devices and processes that deal with small amounts
of fluids (10−6 to 10−9 l) has the potential to significantly change
the way of processing dispersed food systems.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
B.K. Paul, PNNL,2004
MICROFLUIDICS APPLICATIONS
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROFLUIDICS PHYSICS
The behaviour of dispersed phases, either gas–liquid (foams) or liquid–liquid (emulsions), common in many macroscopic food systems is well understood.
At levels below the micrometer scale, some effects negligible at the macroscopic level become important; for example, those related to surface tension, energy dissipation and fluidic resistance.
Moreover, different from the macro‐scale, a special attention must be paid to the wetting phenomena of the fluid on the substrate.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
PRESSURE-DRIVEN FLOW
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
SURFACE TENSION
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
CHAOTIC ADVECTION MIXING
Chaotic advection mixing simulation in a 3D serpentine micromixer
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
DROP GENERATION
Three main approaches for drop generation based on different physical mechanisms are: a) breakup in coaxial-flowing streams b) breakup in cross-flowing streams c) breakup in elongational strained
flows
C. N. Baroud, F. Gallaire and R. Dangla
Lab Chip, 2010, 10, 2032–2045
a)
b) c)
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
HYDRODYNAMIC FLOW FOCUSING
Hydrodynamic flow
focusing can be used
as drop generator
allowing drop control
of frequency and size.
Can be used as well
in diffusion based
processes or
reactions
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
FLOW REGIMES IN FLOW FOCUSING DEVICES
The two principal flow regimes in flow focusing devices are:
DRIPPING AND JETTING.
In the dripping regime, the flow rates are small enough so that the droplet forms immediately after the nozzle. In the jetting regime, a thread or filament stretches far into the outlet channel
Pe
Pi
Pe
J. Berthier & P. Silberzan, Microfluidics for Biotechnology, 2ED, Artech House, 2010.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
DRIPPING MODES IN MICROFLUIDIC FFD
Depending on the relatives values of the driving pressures Pi and Pe, different operating modes appear:
(a) a flow reversal in the central channel if Pe >> Pi;
(b) a droplet mode;
(c) a plug mode — large droplets touching the walls;
(d) annular flow mode —dispersed phase flowing inside the continuous phase;
(e) reversal of the flow in the external channels if Pi >> Pe
Pe
Pi
Pe
J. Berthier & P. Silberzan, Microfluidics for Biotechnology, 2ED, Artech House, 2010.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROENCAPSULATION
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROENCAPSULATION Encapsulation is the packaging of small particles of solid, liquid or gas, also know as the core, within a secondary material, also know as the shell or coating, to form small capsules. Microcapsules are usually classified in Nanocapsules (< 100 nm) and Microcapsules (in the order of microns) In the past encapsulation was used to mask the unpleasant taste of certain ingredients and also to simply convert liquids to solids.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROENCAPSULATION ADVANTAGES
Microorganism and enzyme immobilization.
Protection against UV, heat, oxidation, acids, bases
Improved shelf life due to preventing degradative reactions
Masking of taste or odours.
Improved processing, texture and less wastage of ingredients.
Handling liquids as solids
Growing demand for nutritious foods for Children
Enhance visual aspect and marketing concept.
Farmaceutical controlled and targetted release of active ingredients.
Microencapsulation allows mixing of incompatible compounds.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
COATING MATERIALS
Gums: Gum arabic, sodium alginate, carageenan.
Carbohydrates: Starch, dextran, sucrose
Celluloses: Carboxymethylcellulose, methycellulose.
Lipids: Bees wax, stearic acid, phospholipids.
Proteins: Gelatin, albumin.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROENCAPSULATION PROTECTS
Protection of the active ingredients against:
pH
Oxygen
Osmotic Pressure
High temperature
Shear stress
Enzimatic activity
Improved handling of the active ingredients
Possibility to introduce hydrophilic ingredient in hydrophobic food matrix and vice versa
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
THE SCALES OF FOOD MICROSTRUCTURES AND RELATED SCIENCES
Taken from : J.M. Aguilera, Designing Microstructures for Food Functionality, Presented at CIBUS 2008
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
Spray drying
Coacervation
Emulsion/solvent
extraction
Gelification
Polymerisation
Electrospinning
Technologies
MICRO-NANOENCAPSULATION AT IPT
Microfluidics
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
Microfluidics Food Microstructuring The design of novel food micro‐structures aimed at the quality, health and pleasure markets will probably require unit operations where the scale of the forming device is closer to the size of the structural elements (i.e.0,1–100 μm). One particular technique to provide bioavalability of nutriceutical or controlled release of active principles is Encapsulation.
By combining geometry design of microchannels and fluid flow rate is possible to obtain particles with high size control, reproducibility and low polidispersivity.
Microfluidics is a powerful tool to obtain particles in micro and nanoscale and for encapsulate drugs based on:
Emulsion formation (simple & double)
Foam formation
Mixing
Analytical Measurements
MICROFLUIDICS & FOOD INGREDIENTS
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROFLUIDIC DEVICES IN
MICROENCAPSULATION
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
EMULSIONS: BATCH VS CONTINUOUS
Microfluidic Devices
Mineral Oil
Mineral Oil
Polymeric Solution
Drop Outlet
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROFLUIDIC SINGLE EMULSIFICATION
Using one flow focusing device enable us to obtain single emulsions water/oil with controlled characteristics
Soft Matter, 2007, 3, 986–992
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICROFLUIDIC DOUBLE EMULSIFICATION
Using two consecutive flow focusing devices enable us to obtain double emulsions oil/ water/oil/ with controlled characteristics
Soft Matter, 2007, 3, 986–992
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
ADVANTAGES OF PRODUCING EMULSION VIA MICROFLUIDICS
Formulation flexibility (single & double emulsions) Drop distribution control Less raw material consumption (less surfactant for emulsion
stabilization) Emulsion can stand thermal processes
System free of contamination
Elimination of mixing mechanical forces, emulsions based on microfluidic principles
More portable equipment with less size and volume Less energy consumption Scaling possibility (numbering-up) Maintenance easiness
In Products
In Processes
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
EMULSIONS USING GLASS DEVICES
10 20 30 40 50 60 70 80 90 100 11010
12
14
16
18
20
22
24
26
28
30
32
34
dro
ple
tdim
en
sio
n3
(u
m)
Renex 100 (1%)
Renex 100 (5%)
Single emulsion production (Water-oil) Drop size Vs. input fluid ratio
J. N. Schianti, et al. Emulsion production using glass microfluidic devices, Proc: IBERSENSOR 2010
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
GELATIN EMULSIONS
Gelatin emulsions can be applied to encapsulate vitamin C for drug release.
Thermosensitive hydrogel materials in the MF chip to generate continuous and uniform emulsions.
The gelatin emulsion diameters range from 45 to 120 microns
Chia-Hsien Yeh • Ke-Rong Chen • Yu-Cheng Lin, Developing heatable microfluidic chip to generate gelatin
emulsions and microcapsules, Microfluid Nanofluid, 2013, DOI 10.1007/s10404-013-1193-x
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
3D MICRO MIXERS IN LTCC
3D Serpentine Micromixers can be used for chemical Microreactors in order to fabricate emulsions, particle packaging and nanomaterial fabrication
10 mm
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
IONIC GELATION MICROPARTICLES Techniques such as solvent evaporation microencapsulation, complex coacervation and ionic gelation can be carried out in microfluidic devices, producing particles.
An experimental arrangement with two syringe pumps was used to apply the solutions of polymer and calcium in the proper inlets of microfluidic LTCC devices under test . An oil flow cut the polymeric solution in droplets. These droplets were conducted to the calcium solution, to promove the ionic gelation (30 minutes). Finally after this period, the microspheres were filtered and washed with distillate water, this particles were compared with standard method.
LTCC Devices Tested
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
EMULSIONS OBTAINED
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
PARTICLES OBTAINED
Alvim D I, Cunha M. R, Ré MI, Gongora-Rubio M R, Microfluidic Chip Technology applied on production of Microparticles by ionic gelation for Food application, IFT (Institute of Food Technologists) Annual meeting 2011.
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
Nano particles can be obtained using the anti-solvent nano-precipitation process
COAXIAL FLOW FOCUSING DEVICE FOR PARA NANO PRECIPITATION
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
MICRO-ENGINEERING OF FOOD FOAMS BY MICROFLUIDIC DEVICES
O. Skurtys ∗, J.M. Aguilera, Structuring bubbles and foams in gelatine solutions within a circular microchannel device,
Journal of Colloid and Interface Science 318 (2008) 380–388
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
PLGA MICROPARTICLES A microfluidic approach to prepare poly(lactic-co-glycolic acid) PLGA microspheres by means of LTCC passive micromixers integrated to an emulsion/solvent evaporation process .
Passive LTCC micromixers are integrated to the encapsulation process in two steps.
The first step is the mixing of two immiscible liquids to generate an emulsion.
Secondly, sequential phenomena such as solvent diffusion and crystallisation generate solid particles such as polymeric microspheres for drug delivery.
Organic Phase
Volatile solvent + Active constituent
Protective polymer
Aqueous Phase
Water + Surfactant (1500 mL)
T
P
Step 1 Step 2
Formation of
microemulsion
Evaporation of
the solvent
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
(DCM/BD1/Q36)
PLGA (Poly (DL-lactide co-glycolide) microspheres loaded with BSA (Bovine serum albumin ) ( 750x)
PLGA FOR MICROENCAPSULATION
0
20
40
60
80
0 50 100 150 200 250
Time (hours)R
ele
as
ed
BS
A (
%)
Micromixer ED2 Micromixer BD1 Conventional mechanical agitation
M. Ribeiro-Costa, et al. Preparation of protein-loaded-PLGA microspheres by an emulsion/solvent evaporation process employing LTCC micromixers, Powder Technology Vol-190, p.107–111, (2009)
Comparison of particle release obtained with micromixers and
standard methods (Turrax agitation)
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
ELECTROSPRAY MICRODEVICES
Inner solution
active agent
Outer solution
polymer solution
Particle
collector
High Voltage Power supply
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
DOUBLE VORTEX MICROREACTOR FOR POLYMERIC NANOCAPSULES
The polymer nanocapsules can be obtained by an emulsion-diffusion process, that is useful to encapsulate actives.
The microfluidic reactor contains double vortex geometry with the purpose to produce an emulsion on the first vortex and a dilution process on the second one.
Vortex geometry is useful for mixing process and has the advantage to work with higher fluid flow rates. In the first experiments we obtained particles with 160 nm of sizes, with low polidispersity and in higher flow rates (in the range of 15 mL/min).
MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS
CONCLUSIONS
Encapsulation in food fields is becoming important for his many applications. This could lead to a route adapted to the micro encapsulation process in order to design capsule , emulsion or foam with size and morphology controlled in continuous process.
In fact microfluidics encapsulation allow an encapsulation:
Effective
Cheaper
With capsules size of the order of several microns
In spite of issues related to the numbering‐up, microfluidics provide to food technologist an additional important tool for ensure food’s quality and safety as well.