TOPICS IN (NANO) BIOTECHNOLOGY

Microfabrication techniquesJanuary 9th, 2007

PhD Course

Introduction

Microsystem components

Definition

Terminology

Benefits of Microsystems

Benefits of microsystems

Benefits of Microsystems

Benefits of Microsystems

History

Applications

Example...

Microsensors

Microactuators

Microfluidics

Microsystem Applications

Concentrated System in a Single Box

Bipolar, BCD, CMOSBiCMOS, VIP,µ-Machining

Power Management

InformationProcessing(Super Integration)

MultifunctionPeripheral (System

Oriented Tech.)

Data Acquisitionand Conversion

Bipolar, CMOS,RF-BiCMOS,µ-Machining

Central Processing(µP, DSP)

Digital CMOS

PowerActuators

Bipolar, BCD,CMOS, HVCMOS,VIP, µ-Machining

Memories

CMOS, Flash,DRAM, µ-Machining

Line, Batteries,Alternators, Solar Cells, Fuel Cells

Sensors

Antennas

Keyboards

LineInterfaces

Switches

Clock Clock

Clock

Lamps

Motors

Displays

Solenoids

Speakers

CRTs

Inkjets

Antennas

Microfabrication - applications

Microfabrication - applications

History of Lab-on-a-Chip-Systems and µTAS

1975: Gas chromatograph by S. Terry (Stanford-University)

1990: Micro channel liquid chromatograph

1990: „Micro Total Analysis System (µTAS)“ introduced by A. Manz

1992: Development of first capillary electrophoresis chips

1994: massive increase of publication about Lab-on-a-Chip and µTAS

1998: First PCR-micro chips

End 90th: Start of several Lab-on-a-Chip- and Bio-MEMS-companies

Applications of Lab on a Chip

• Medical diagnostics (PoC, …)

• Pharmaceutical development (HTS, HCS, …)

• Environmental analysis (monitoring, portable analysis, …)

• Food analysis

• Process control

• Process development (screening)

• Small scale production (e.g. fine chemicals, rare molecules, …)

µTAS

Design Scheme for a Lab on a Chip / µTAS

Sample inlet

Target identification• DNA primer• Antibody• Aptamers

Amplification• Enzymatic reaction• PCR / NASBA• “Secondary reaction”

Sample preparation• Cell sorting• Filtration• Washing• Cell lysis• Purification

Sensor

• Electrochemical / Amperometric / Voltametric / Impedance /…

• Optical / Fluorescence / Absorption /…

• Mechanical / Oscillator / Deflection / …

• Temperature

Instrument output

User

Lab-on-a-Chip Systems

Generic Characteristics

• Integrated

• Miniaturized (Small channels)

• Automatic operation

Lab-on-a-Chip Systems: Derived Characteristics

• Low chemistry consumption

• Laminar fluidics

• High control (no chaotic processes)

• Fast diffusion (fast operation for diffusion limited processes)

• Easy parallelization

• “New” effects due to smaller dimensions

• Higher production costs (with respect to system volume)

What is special in µ-fluidics?… At least one characteristic dimension in the

micron range (1-100 µm)

• Inertia has low effects

• Surface tension is dominant

• Gravity has minor importance

• Mixing is due to diffusion mainly (not due to convection)

• Fast heat transfer due to small distances

• High Surface-To-Volume: Inhomogeneous reactions (surface reaction) are essential (e.g. catalysis, sensors, unspecific binding)

• …

Challenges during developmentPerformance

• Sensitivity

• Selectivity

• Reproducibility

Hardware

• Speed of development

• Availability of sufficient systems /chips

Know how

• Intellectual property situation

• Theoretical understanding

Challenges for commercialization

• Robustness

• Reproducibility (QM, GMP, …)

• Approval of the product (CE, FDA, …)

• Self life

• Pricing

• Availability of sufficient systems (producibility of the product)

Reaction

Protocol

• Metering of sample

• Mixing of sample and reagents

• Optical detection

Detection principle

• Absorption at 545 nm

Lab-on-a-Chip an Example

Commercial Systems: Glucose detection

Roche; AccuCheck

Glucose in blood

Lifescan; SureStep Flexx

Glucose monitor

Commercial Systems: Blood Analyzer

Abbott; i-STAT

Siemens; Quicklab

CARESIDE

Analyzer

Commercial SystemsAdvalytix

1 µl PCR slides for forensic

Commercial Systems

Nanostream; Velove microparallel LC

(micro parallel liquid chromatography)

Tecan; LabCD(development stop 7.05)

Gyros; Gyrolab

Commercial Systems

Agilent/Caliper

Product: Bioanalyser

Electrophoresis

Commercial Systems

Aclara Biosciences

Product: Labcard

(Electrophoresis)

Microfabrication Techniques

Overview

Overview • Micromachining technologies

• Bulk micromachining• Surface Micromachining

• Basic Processes• Lithography• Wet etching• Dry etching• Deposition

UV-lithography • Lithography refers to a process whereby the

top layer on a wafer is selectively removed or patterned.

• Photolithography; light-stone-writing in greek

UV-lithography

Laser Sources

Wmin = k1 .

NA

Types of UV-lithography

UV-lithography

UV-lithography • Mask making

• Resist spinning

• Alignment of wafer and mask

• Resist tone, Tg, critical dimensions

• Lithography resolution

• Depth of Focus

• Resist wall profile manipulation

• Clean-rooms, wafer cleaning

• Process sequence

UV-lithography

• Resist applied to the surface using a spin-coating machine, which holds the wafer of a semiconductor, using a vacuum, and spins it at high-speed (3000-6000 rpm) for a period of 15-30 seconds.

• Preparation concluded by a pre-bake, where wafer is generally heated in a convection oven and then a hotplate to evaporate resist solvent

Photoresist

Developer

Process

UV-lithography

• Fiducals are patterns used for alignment on wafer steppers. These fiducials are located outside of the array or fields.

• Alignment of the mask is critical and must be achieved in the x-y plane

• Double alignment is especially important in the fabrication of micromachines

Advanced Lithography

• Electron-beam lithography

• Ion beam lithography

• X-ray lithography

• Extreme UV-lithography

Wmin = k1 .

NA Reduce k1

Reduce

Increase NA

Advanced Lithography

Advanced Lithography

Wavelengths started with the g-line (436 nm) of Hg - good down to 0.4m

Next came the 365nm i-line in the near-UV - this took us down to 0.3m

BUT no light bulb that emits enough intensity at wavelengths considerably smaller than 365nm

The solution was excimer lasers - 248nm, 194nm and 157nm (deep UV lithography)

this spelt …… the END of UV-lithography!

Advanced Lithography

Extreme UV Lithography

Technology breakthrough - 13.4nm wavelength of this light is more than 10 times shorter - allows patterning of lines below 50nm dimensions

Intel leading a consortium of six semiconductor companies called the EUV LLC to develop this technology

Extreme UV Lithography: Sources

Electron beam Lithography

Pattern directly written into resist by scanning e-beam

Eliminates the diffraction limits of optical lithography

Performance records:

- in PMMA (organic resist): 7nm

- in AlF3(inorganic resist): 2nm

Optical Electron Beam

Advantage

Low ~High precision Fast exposure speed Relatively low cost

No diffraction Easy to control Available for small features

Disadvantage

Light diffraction Alignment problem Debris between mask and wafer

Needs vacuum High system cost Slow

UV vs E-beam Lithography

Ion-beam Lithography• Variation of the electron-beam lithography technique - uses a focused ion beam instead of an electron beam

• The ions are field extracted from a liquid metal ion source (LMIS) that consists of a tungsten needle with a radius of curvature of 1mm that is wetted by a liquid metal.

• The application of an electric field (>108cm/V) to the wetted tip results in the formation of a cone with a radius of curvature of 10nm from which the ions are field extracted

• The extracted ions are accelerated, collimated and focused by a series of apertures and electrostatic lenses

• Spot-sizes of 10nm to 500nm are possible.

Ion-beam Lithography

X-ray Lithography

As shown in this figure, the penumbral blur, , on the adge of the resist image is given by:

= ag/L

a is the diameter of the x-ray source

g is the gap between mask and wafer

L is the distance from the source to the x-ray mask

LIGA

© M.J, Madou

LIGA

Allows the creation of 3-D structures with excellent tolerances and extremely high aspect ratios

Main drawback – very expensive to implement

Soft LithographyTransfer of a self-assembled monolayer precursor with an elastomeric stamp onto a substrate

1) A master is generated by photolithography and a stamp is obtained by casting of an elastomer (PDMS etc.)

2) A pattern is generated by stamping a SAM on a substrate

Ink-jet micromachining

Bulk, surface, DRIE

Bulk micromachining • As the name implies, bulk micromachining

focuses on the creation of patterns or features within the bulk of some sort of starting material. In doing so, we rely on the physical structure of the material in question (amnogst other variables) to control the shape of these features

• Although materials such as quartz, pyrex, GaAs, Ge, etc. Are used as teh starting material for this technology, the material that is most commonly used is silicon

• Silicon has well understood lattice structure composed of two interpenetrating face-centered-cubic (FCC) lattices

Silicon

Miller Index

Miller Index are symbolic vector representations of the orientation of the atomic planes that make up the crystal lattice

Miller Index

Greater density of atoms slower etch rates

Silicon wafer

• Silicon boules are grown using a seed material of known orientation. The boule is subsequently sliced into wafers that will have this same orientation.

• Silicon etchants and silicon wafer orientations are selected to create the necessary features within the bulk of the wafer.

Silicon wafer

Bulk micromaching

Bulk micromachining

• Anisotropic etchants such as KOH:H2O (alkaline) tend to

etch different crystal planes at different rates, thus giving rise to structures having well defined sidewalls with precise and predictable angles of inclination (very little undercutting).

Anisotropic etchants

Examples

• Isotropic etchants such as mixtures of HF:HNO3:CH3COOH (acidic) tend to etch different crystal planes at the same rate, thus giving rise to rounded structures with much undercutting.

Isotropic etchants

Isotropic etchants

Wet isotropic etching

Examples of etchants

Examples of etchants

Etch Stop

Dry isotropic etching

Dry anisotropic etching

Deep reactive ion etching

Deep reactive ion etching

Surface micromachining • In the case of surface micromachining,a different

approach is taken in that rather than etching into the bulk of the starting material, structures are built up on the substrate surface

• These structures are created via the repetitive addition of layers selected for their various material properties, followed by the selective removal of these layers in a specific sequence.

• The vast array of materials that can be “deposited” includes polysilicon, silicon nitride, oxide, polyimide, metals, etc.

Deposition

a) Chemical Vapor Deposition (CVD) systemsWhich rely on the chemical reaction of the constituents of a vapor phase at the substrate surface to deposit a solid film on this surface.

b) Physical Vapor Deposition (PVD) systemsWhich directly deposit the source material onto a given substrate in a “line-of-site impingement type deposition”.

Deposition systems may be divided into two groups:

a) CVD: Common film types & sample chemistries

Polysilicon:

Silicon Nitride:

Silicon Dioxide:

Deposition

DepositionTable 1. APCVD, LPCVD, and PECVD Comparisons          CVD

ProcessAdvantages Disadvantages Applications

APCVD Simple, Fast Deposition,Low Temperature

Poor Step Coverage,Contamination

Low-temperature Oxides

LPCVD Excellent Purity,Excellent Uniformity,Good Step Coverage,Large Wafer Capacity

High Temperature,Slow Deposition

High-temperature Oxides, Silicon Nitride, Poly-Si, W, WSi2

PECVD Low Temperature,Good Step Coverage

Chemical and Particle Contamination

Low-temperature Insulators over Metals, Nitride Passivation

Deposition

b) Physical Vapor Deposition (PVD) systems

– In these types of thin film deposition systems, the source materials to be deposited take on a variety of forms:

• Solid• Liquid• Vapor

– In the case of PVD systems, the materials to be deposited are physically deposited using a variety of methods including:

• Thermal Evaporation • Sputtering• Etc. (Laser Ablation, Molecular Beam Epitaxy)

Deposition

a) Physical Vapor Deposition (PVD) systems -

continued

– The range of materials that may be deposited using these methods include:

• Metals such as:

– Al – Cu– Au– Ag– etc.

• Compound & hard materials such as:

– Cr– TiN– CrN– AlCuSi– etc.

Deposition

– The material to be deposited is placed in a crucible within a high-vacuum chamber.

– After the chamber is pumped down, the source is heated via (typically) resistive or e-beam heating. The material is heated to its boiling point such that it sublimates onto all exposed surfaces in the vacuum chamber.

– The amount of material deposited is controlled via a thickness monitor which is placed within the deposition chamber.

– The source material must be of high purity.

– Vacuum levels are on the order of 10-5 to 10-7 Torr.

Thermal Evaporation –

Resistive Heating

Thermal Evaporation –

e-Beam

Thermal Evaporation - General

Deposition

Thermal Evaporation - drawbacks

– Resistive heating is the simplest method of evaporating metals such as Al

or Au, but it is also the “dirtiest” in that contaminants which find their way

onto the filament tend to be evaporated along with the metal.

– The purity issue can be addressed via e-beam evaporation since the

cooled, non-molten high-purity material to be deposited acts as a crucible

during the process (see schematic on previous slide).

– In the case of resistive heating, temperature uniformity across the filament

is difficult to control and therefore, evaporation uniformity onto the

substrates may be a problem. This is not an issue with e-beam

evaporation

– E-beam evaporation may cause surface damage due to ionizing radiation

and/or X-rays (@ voltages above 10kV, the incident electron beam will

give rise to X-ray emission).

Deposition

Sputtering

Sputtering – principle of operation• A solid slab (ie., target) of the material to be deposited is placed in a

vacuum chamber along with the substrate on which the deposition is to

take place.

• The target is grounded.

• Argon gas is introduced into the chamber and ionized to a positive

charge.

• The Ar ions bombard the target and cause the target atoms to scatter,

with some of them landing on the substrate.

• The plasma is composed of the Ar atoms, Ar ions, the sputtered

material, gas atoms and electrons generated by the sputtering process.

• Allows the deposition of a large assortment of materials on any type of

substrate

Deposition

Deposition: sputtering

Sputtering – advantages/disadvantages

M.J. Madou

Deposition

Surface micromachining

Surface micromachining

Surface micromachining

Sealed cavity

Examples

Examples

Bulk vs Surface

• Both bulk and surface micromachining concepts are most often combined to create both intricate and simple devices and systems.

• Other observations (M.J. Madou):

Process Flow

Process Flow

Process Flow

Process Flow

Process Flow

http://www.thoughtequity.com/video/clip/1659037_021.do