Sk microfluidics and lab on-a-chip-ch2

Microfluidics and Lab-on-a-Chip for biomedical applicationsChapter 2 : Principles of Microfluidics.

By Stanislas

CNRSUniversité de Lyon, FRANCEStansan International Group

CONTENT

Chapter 1: Introduction.

Chapter 2 : Basic principles of Microfluidics.

Chapter 3 : Basis of molecular biology and analytical tools.

Chapter 4 : Micromanufacturing.

Chapter 5 : Lab-on-a-Chip & applications.

Chapter 6 : Cancer diagnostics and monitoring.

Fluid Transport at Different Dimension Scale

Microfluidics

Advantage of Microfluidics

Why study Microfluidics ?

Applications of Microfluidics Systems

Microfluidics – Progress in Miniaturization

Fluids - Types of Flow

Fluids - Types of Flow

Poiseuille Flow (Parabolic)

Microfluidic systems Pressure Driven Flow

There are two common methods by which fluid actuation through microchannels can be achieved. In pressure driven flow, in which the fluid is pumped through the device via positive displacement pumps, such as syringe pumps. One of the basic laws of fluid mechanics for pressure driven laminar flow, the so-called no-slip boundary condition, states that the fluid velocity at the walls must be zero. This produces a parabolic velocity profile within the channel.

Microfluidic systems Pressure Driven FlowInfluence of Channel Aspect Ratio

Three-dimensional velocity profile of fluid in a microchannel with an aspect ratio of 2:5

Three-dimensional velocity profile of fluid in a microchannel with an aspect ratio of 50:1.

Pressure Driven Velocity Profiles

Reynolds Number

Reynolds Number

Reynolds Number

Reynolds Number

Reynolds Number

Viscosity

Viscosity

Viscosity

Diffusion in Fluids

2D solution for the diffusion of biotin (D = 340 µm2/s, left image) and albumin (D = 65µm2/s, right image) through a T-sensor. A normalized concentration of 1.0 enters at the left inlet where the velocity flow rate is 125 µm/s. Buffer enters at the right inlet at the same velocity.

Diffusion

Microfluidics at macro - scale

The H-filter

The H-filter is an inherently microfluidic device. Developed at UW in the mid-90's, the H-filter allows continuous extraction of molecular analytes from fluids containing interfering particles (e.g., blood cells, bacteria, microorganisms, dust, and viruses) without the need for a membrane filter or similar component that requires cleaning or replacement.

Principle: differences in the diffusion coefficient of particles.

The principle of the H-filter is shown at upper left. In the center of the device, streams move in parallel, and diffusion causes equilibration of small molecules across the channel, whereas larger particles do not equilibrate during the transit time of the device. Modified streams separate at the right edge..

The H-filter

Scanning fluorescence image : note that the Rhodamine solution doesn’t enter into the horizontal channel

(only a small diffusion is visible)

Rhodamine solution were introduced into the vertical channel

(A) Experimental set-up formicroalbuminuriadetermination.

(B) Microchip layout with inlets for AB 580 (1),and HSA (2), mixing channel (3), detection chamber (4), outlet (5) and orthogonal detection point (6).

Example : Design a long mixing channel

Requirements : Mix ethanol completely with water in a parallel micromixer with two inlets (Y-mixer) at room temperature. Flow rate for both liquids are 10 μl/min. D of ethanol in water (25 °C)= 0.84×10-5 cm2/s.

Find : The required length of the mixing channel with channel diameter of 100 μm×100 μm.

Too much for microsystems !!!

MixingMixing is a basic process required for many biological applications. At the microscale, laminar flow conditions prevent mixing except by diffusion.

In a microfluidic device, there are two ways of mixing fluid streams : Passive mixers and active mixers.

Passive mixers: use channel geometry to fold fluid streams to increase the area over which diffusion occurs, such as: distributive mixer, static mixer, T-type mixer, and a 3D mixer.

Active mixers: Active mixers use external sources to increase the interfacial area between fluid streams. Examples of active mixing include a PZT-based mixer, electrokinetic mixers, a chaotic advection mixer, and magnetically driven mixers.

Misromixer – Design Consideration

Mixing Passive - examples

Splits the fluid streams and then recombines them.

3-D micromixer.

Example of an active chaotic advection mixer

Principle Simulation examples for 2 different temps

Active chaotic advection mixer developedat ECL (France) for hybridization of DNA BioChips [F. Raynal et al., Phys. Fluids, 16, 9, 2004]

Surface Tension

The cohesive forces among the liquid molecules are responsible for the phenomenon known as surface tension. In the bulk of the liquid, each molecule is pulled equally in every direction by neighboring liquid molecules, resulting in a net force of zero. The molecules at the surface do not have other like molecules on all sides of them and consequently they cohere more strongly to those directly associated with them on the surface. This forms a surface "film" which makes it more difficult to move an object through the surface than to move it when it is completely submerged.

Surface tension has the dimension of force per unit length, or of energy per unit area. The two are equivalent.

Surface Tension

Magnitude of Surface tension in a liquid

Capillary Effects

Capillary Effects

Capillary Effects

Hydrophilic - HydrophobicMolecules that form hydrogen bonds with water are hydrophilic and those that can't are hydrophobic.

Molecules that dissolve or interact with water, such as carbohydrates, are said to be hydrophilic, water loving, but these molecules just dissolve in water, because they form H-bonds with water molecules. Each hydroxyl (-OH) group on a carbohydrate can make hydrogen bonds to three different water molecules. The hydrogen can bond to a pair of valence electron on the oxygen of water and each of the two pairs of valence electrons of the hydroxyl can bond to a hydrogen of water. Most of the molecules within cells can form H-bonds and are hydrophilic.

Typical hydrophilic molecules include :· proteins, · carbohydrates, · nucleic acids (DNA and RNA), · salts (form ionic bonds), · small molecules of metabolism (e.g. glucose, amino acids, ATP)

Hydrogen Bond Formation is Essential for Interactions with Water

In contrast, fats that float and don’t dissolve in water are called hydrophobic, but that doesn’t mean that fats hate water or are pushed away from water, it simply means that fats can’t form hydrogen bonds with water. Since bonding means that energy is released as molecules come into contact, then water molecules forming hydrogen bonds are in a lower energy state than water molecules in contact with a hydrophobic molecule, such as a fat. Random movement of a mixture of fat and water will eventually result in the water molecules sharing the minimal possible surface with the fat, because that is the lowest energy configuration.

Typical hydrophobic molecules include:· fats, · steroids, · lipids, · aromatic compounds (such as some drugs).

Hydrophobic Molecules Don’t Make Hydrogen Bonds with Water

Contact angle of liquid on solid surface and wetting

Surface Roughness and Contact Angle

Wettability and Roughness

Transport ProcessesType of Transport :

Pressure driving flow (often generated mechanically by a pump).

Entropy-driven transport (occurs only if a fluid is more disordered after transport than before), e. g. diffusion.

Gradient induced flow (temperature gradient or concentration gradient).

Electrophoresis flow.

Electroosmosis flow

Dielectrophoretic flow

Electroosmotic and Electrophoretic Flow

Electroosmotic flow : Mobile ions present close to the walls drag the entire liquid column towards one of the electrode.

Electrophoretic Flow : Electrostatic forces moves individually each ion in the direction depending on the charge.

Total Electrokinetic Mobility of each molecule = Electroosmotic Mobility + Electrophoretic Mobility

Electrophoretic Flow



Electrophoresis

Microfabricated CE

Pressure driven flow and Electroosmotic Flow

Charges very close to walls move with the field and drive the entire fluid through the channel.

Can obtain uniform velocity profile.

Pressure driven flow and Electroosmotic Flow

Glass/Liquid interface and Electroosmotic Flow

1)A glass capillary or channel

2) At the surface of the glass are silanol groups (-Si-OH), which, depending on the pH of the buffer solution, are deprotonated to a greater or lesser extent (pK = 6).

3) Deprotonation results in charge separation (pK = 6).

- Negative charges (-Si-O-) immobilized on the wall.- Protons immediately adjacent to the wall.

4) Diffuser layer: negative and positive charge carriersform further into the bulk of the solution.

5) Fixed-layer and diffuse layers: electrical double layer





Zeta potential : the potential atthe shear plane between thefixed stern layer and thediffuse Gouy-Chapman layer.

Dependencies of the Zeta potential :- The chemical composition of the wall (material, dynamic or permanent coating, etc.)- The chemical composition of the solution (pH,ionic strength, additives etc.)- Temperature

Glass/Liquid interface and

Electroosmotic Flow

:1) When an electric field is applied the mobile positive charges drag the entire liquid column towards the cathode-electroosmotic flow.

2) Electroosmotic mobility :

3) Electroosmotic velocity :

4) Advantages : simple, uniform velocity distribution across the entirecross section of the channel.

5) Debye length (the thickness of the double layer)


Dielectrophoretic Force

AC Electrokinetics: Dielectrophoresis (DEP)

Dielectrophoresis (DEP)

Dielectrophoretic Mobility

Microfabricated DEP

DEP : Electrode Design

Example: Single Cell Cage

DEP Applications

Example : Molecular Separation Using DEP

Valves and PumpsPumps : Devices to set fluids into motion.Valves : Devices to control this motion.

Type of valves :1) Passive valves: utilizing energy from the flow2) Active valve: needing external energy to function

Passive valve :Passive valve devices normally consist of either cantilever or membrane on the silicon surface, which open and close to enable and disable fluid flow during forward and reverse pressures.

Active valves :The actuation principles : pneumatic, thermopneumatic, piezoelectric, electrostatic, shape memory alloy, electromagnetic...

Electroosmotic Pumping

Electroosmotic Pumping

Electroosmosis Pump

Electrostatically Actuated Micropump Example

Passive valve examples

Thermopneumatic valve example

Microreactors

Liquid-Phase Reactors

Gas-phase reactors

Microneedles

Stratum corneum (SC): a dead tissueViable epidermis (VE): It consists of livingcells which have blood vessels capable oftransporting drugs, but contains very fewnerves (painless).The microneedle should penetrate intothe skin about 100 μm.

Microneedles fabricated by fs laser

Drug Delivery

(a) Bifurcating channel geometry used to halve droplets at each junction(b) Pillar in channels demonstrates asymmetric fission of water-in-oil droplets(c–e) Active fission of droplets using DEP through surface electrodes in EWOD system

DIGITAL MICROFLUIDICS

Nanofluidics is the study of the behavior, manipulation, and control of fluids that are confined to structures of nanometer (typically 1-100 nm) characteristic dimensions. Fluids confined in these structures exhibit physical behaviors not observed in larger structures, such as those of micrometer dimensions and above, because the characteristic physical scaling lengths of the fluid, (e.g. Debye length, hydrodynamic radius) very closely coincide with the dimensions of the nanostructure itself.

When structures approach the size regime corresponding to molecular scaling lengths, new physical constraints are placed on the behavior of the fluid. For example, these physical constraints induce regions of the fluid to exhibit new properties not observed in bulk, e.g. increased viscosity near the pore wall; they may effect changes in thermodynamic properties and may also alter the chemical reactivity of species at the fluid-solid interface.

All electrified interfaces induce an organized charge distribution near the surface known as the electrical double layer. In nanometer dimensions the electrical double layer may completely span the width of the nanopore, resulting in dramatic changes in the composition of the fluid and the related properties of fluid motion in the structure.

Nanofluidics

Structure for Single DNA Observation

Structure for Single DNA Observation

300 x 140 nm channels

Fluorescent images showing the stretching of 103 kb DNA in the nanofluidic channels. DNA stretching reaches about 95%, and in some cases 100%. The scale bar is 20 µm.

Creating a Pore of 20nm

Experimental set-up

Knudsen Number

The Knudsen number is useful for determining whether statistical mechanics or the continuum mechanics formulation of fluid dynamics should be used: If the Knudsen number is near or greater than one, the mean free path of a molecule is comparable to a length scale of the problem, and the continuum assumption of fluid mechanics is no longer a good approximation. In this case statistical methods must be used.

Diffusion in Nanofluidics

Micro-Particle Image Velocimetry (micro-PIV) :Experimental investigates of the flow behavior of

blood in microchannels.

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Sk microfluidics and lab on-a-chip-ch2