COMUNICAÇÃO TÉCNICA - escriba.ipt.brescriba.ipt.br/pdf/172088.pdf · A série Comunicação Técnica compreende trabalhos elaborados por técnicos do ... three floors • Clean

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

mailto:[email protected]

MICROENCAPSULATION APPLIED TO FOOD INGREDIENTS

SUMMARY

Introduction

MicroTechnology

Fabrication of MicroFluidic Devices

Chemical Process Intensification

Microfluidics

Microencapsulation

Microfluidic Devices in Microencapsulation

Conclusion


INTRODUCTION


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


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


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


MICROTECHNOLOGY


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.


• 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


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.


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


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


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.


FABRICATED MICROFLUIDIC DEVICE


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)


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


PROCESS INTENSIFICATION THROUGHT MINIATURIZED CHEMICAL PROCESSES

Miniature reaction and other unit operations,

Have advantages over conventional chemical systems

Yesterday Today Tomorrow (Today in Merck)


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


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.


LESS ENERGY CONSUMPTION

Micromixers consume less energy for stable emulsion production compared to conventional stirrers

Source: Bayer


MICROFLUIDIC APPLICATIONS

Fluid Management Systems

Micro Analytical Systems

Micro Reaction Systems

Micro Heat Exchange Systems


MINIATURIZED CHEMICAL PROCESS SCALE-OUT

Scale-Up Scale-out

NUMBERING-UP NEW DESIGN


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


MICROFLUIDICS


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.


B.K. Paul, PNNL,2004

MICROFLUIDICS APPLICATIONS


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.


PRESSURE-DRIVEN FLOW


SURFACE TENSION


CHAOTIC ADVECTION MIXING

Chaotic advection mixing simulation in a 3D serpentine micromixer


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)


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


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.


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


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.

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http://images.google.com.br/imgres?imgurl=http://jornale.com.br/mirian/wp-content/uploads/2009/02/cosmeticos1.jpg&imgrefurl=http://jornale.com.br/mirian/?p=3607&usg=__3AaUtIVRpvnt4SrSN13PBaPYKo0=&h=244&w=226&sz=46&hl=pt-BR&start=3&um=1&tbnid=mVfk7rguxEMA1M:&tbnh=110&tbnw=102&prev=/images?q=cosm%C3%A9ticos&hl=pt-BR&rlz=1T4SKPB_pt-BRBR290BR290&um=1

http://images.google.com.br/imgres?imgurl=http://www.ebs-santana.pt/clubealimentacao/images/stories/roda_alimentos.jpg&imgrefurl=http://www.ebs-santana.pt/clubealimentacao/&usg=__GwV0PmwTWRH77Qv8Utki1z5o4yQ=&h=515&w=517&sz=53&hl=pt-BR&start=1&um=1&tbnid=9KopBF4InfwfWM:&tbnh=130&tbnw=131&prev=/images?q=alimentos&hl=pt-BR&rlz=1T4SKPB_pt-BRBR290BR290&um=1

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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.


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 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


THE SCALES OF FOOD MICROSTRUCTURES AND RELATED SCIENCES

Taken from : J.M. Aguilera, Designing Microstructures for Food Functionality, Presented at CIBUS 2008


Spray drying

Coacervation

Emulsion/solvent

extraction

Gelification

Polymerisation

Electrospinning

Technologies

MICRO-NANOENCAPSULATION AT IPT

Microfluidics


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


MICROFLUIDIC DEVICES IN

MICROENCAPSULATION


EMULSIONS: BATCH VS CONTINUOUS

Microfluidic Devices

Mineral Oil

Mineral Oil

Polymeric Solution

Drop Outlet


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


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


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


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


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


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


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


EMULSIONS OBTAINED


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.


Nano particles can be obtained using the anti-solvent nano-precipitation process

COAXIAL FLOW FOCUSING DEVICE FOR PARA NANO PRECIPITATION


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


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


(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)


ELECTROSPRAY MICRODEVICES

Inner solution

active agent

Outer solution

polymer solution

Particle

collector

High Voltage Power supply


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).


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.


Mário Ricardo Gongora-Rubio

[email protected]

Documents

COMUNICAÇÃO TÉCNICA - escriba.ipt.brescriba.ipt.br/pdf/172088.pdf · A série Comunicação Técnica compreende trabalhos elaborados por técnicos do ... three floors • Clean