Intro BME

Introduction and Overview of the Class

生物医学工程导论
李晨钟 教授
Prof. Chenzhong Li

微信:Chenzhong_li

生物光电子和生物芯片研究室
香港中文大学 ，深圳
Department of Biomedical Engineering
Chinese University of Hong Kong，Shenzhen

2023 秋课BME3001
An Introductory to
Microchips,
Lithography,
and Bio-Microchips
23.10.17
BME 3001
Xinyuan LUO
Shiyu TANG
Qingyuan LI
Introduction
Microchip:
• A microchip, which is an integrated circuit, consisting of
semiconductor materials such as silicon.
• It incorporates multiple electronic components like transistors,
resistors, capacitors.
• Microchips are the fundamental blocks of devices, including
computers, Biological instruments and industrial machinery.
Classification
1. Consumer Electronics Microchips:
Like Microchips in smartphones and computers, it handle various
functions such as processing, memory, and communication,
enabling the them to execute apps, internet browsing, and media
playback.
Classification
2. Industrial Microchips: Industrial microchips play a vital role in
manufacturing and automation environments in factory.
Industrial robots use microchips for precise movement control,
sensor integration, and decision-making capabilities, enhancing
efficiency and productivity.
3. Medical Microchips: Medical microchips are crucial components
in various medical applications.(Microfluidic Chip, Nucleic Acid
Biochips)
Microchips in diagnostic devices enable tasks such as imaging
processing, data analysis, and signal interpretation, aiding in
disease diagnosis and research.
Structure Difference
Consumer Electronics Microchips:
• CPU: It use high-performance general-purpose processors (such as ARM
stucture) to support multitasking and complex computations. These processors
have high clock frequencies and computational capabilities to meet the
demands of rapid response and high performance.

• Graphics Processing Unit (GPU): Consumer electronic products, especially

gaming consoles, smartphones, and TVs, often require powerful graphics
performance. It usually integrate high-performance GPUs to support graphics
and smooth video playback.
Structure Difference
• 2. Industrial Microchips:
• Reliability: Industrial systems operate in challenging
environments (car accident) and require microchips that can
withstand harsh conditions(cold environment) to ensure stable
operation.
• Real-time Control: Industrial microchips are optimized for
precise and fast response, enabling seamless automation and
control in manufacturing equipment and robotics.
• Customized Interfaces: Industrial microchips offer customizable
input/output options and communication protocols to
accommodate diverse industrial equipment requirements.
Structure Difference
• 3. Medical Microchips:
• Biocompatibility: Medical electronic devices must be
biocompatible to ensure they can safely interact with the human
body. Medical microchips are often made from materials that are
compatible with biological tissues and fluids, minimizing the risk
of adverse reactions.
• Sensors and Bio-interfaces: Medical microchips frequently
integrate sensors and bio-interfaces to monitor biological signals,
such as heart rate or glucose levels. These specialized features
enable precise data collection and analysis, aiding in diagnostics
and patient monitoring.
Advantage
• In summary, consumer electronics microchips offer a high-
performance capabilities for devices, so it need higher
effectiveness, and means the most difficulty to design and
manufacture. Industrial microchips focus on robustness, real-time
control, and customized interfaces for automation, while medical
microchips prioritize biocompatibility, specialized sensors and
bio-interfaces to support various medical applications.
INTRODUCTION
How to make microchips?

1 Wafer Preparation
2 Photolithography
Step 1-6 Wafer Preparation
1 Polysilicon
Silica (ore)  Silicon Ingots stacking
2 Ingot growing

(impurity)

 Polycrystalline Silicon (textured

silicon rod)

Simens-Verfahren method
 Step 1-6 Wafer Preparation
1 Polysilicon
stacking
Czochralski process 2 Ingot growing

seed
polycrystallin
e
silicon

Polycrystalline Silicon (textured silicon rod)

 Monocrystalline Silicon (mirror-like silicon rod)
Step 7-15
Wafer Preparation 5 Edge grinding rounding the edges
of the wafer
(also the subsequent quality inspection steps)
6 Lapping pressing heavy supposition
plate together with an abrasive
3 Ingot grinding and ingot
cropping 7 Etching
-- Rod  Sliced Silicon Sheets (a 8 Double side grinding
flat surface: flat/notch) 9 Rapid Thermal Process
(RTP)
10 Polishing
11 Cleaning
12 Inspection
13 Particle counting
14 EPI growing
15 Final product packing
4 Wire sawing
Photolithography
-- uses a beam of photons to transfer a pattern written on an optical mask to the substrate surface. A
wafer will go through the photolithographic step in the order of 20–30 times.

1 A liquid polymer called photoresist is spun

on the surface while the wafer is kept rotating
at high speed.
-- Rotation can make the photoresist layer
very thin and flat.

2 After a thermal bake-out, the substrate is

introduced in an optical projection tool called
stepper/scanner.
Photolithography
-- uses a beam of photons to transfer a pattern written on an optical mask to the substrate surface. A
wafer will go through the photolithographic step in the order of 20–30 times.
3 During exposure, the photoresist material
undergoes some light-triggered chemical
reactions. Positive
The resist can be used as a patterning mask for photoresist
etching, deposition or implantation.
4 The wafer is immersed in a developer solution
to selectively remove either the exposed or
unexposed photoresist, leaving behind a
patterned layer that corresponds to the mask’s
features.
Two types of photoresists after UV light
exposure:
positive (more soluble) & negative (less soluble)
Additional Processes
1 During Photolithography:
Ion implantation (introducing dopants,
change electrical properties)
-- Examples
Boron (B): Boron is used as a p-type dopant. When introduced into
silicon, it creates "holes" in the crystal structure, which act as positive
charge carriers.
Phosphorus (P): Phosphorus is used as an n-type dopant. It introduces
additional electrons into the crystal structure, which serve as negative
charge carriers.

2 During Wafer Preparation:

Chemical vapor deposition, CVD (to
deposit thin films, coatings, or layers of
various materials onto substrates)
--Example: it can be used to deposit dielectric materials for insulating
layers or to create metal interconnects.
The Photolithography Machine
(Video produced by Intel, 2:00-4:00, 2minites)

--UV light generation

Microfluidic chip and Microarray
Microfluidic chip(Lab-on-chip)
• What is the microfluidic?
-Process liquids through tiny channels (microscale or nanoscale)
-The interdisciplinary fields: refer to materials, biomedical engineering, fluid physics and
microelectronics.
 Application
1.Miniaturized, integratable, high-
throughput and automated
biochemical analysis.

2.Fabrication of biomaterials with

precisely controlled structures and
compositions.

3.Construction of organ-on-a-chip
systems with specific organ features
and functions.
Advantags of microfluidic systems
• Cost reduction.
• Save time.
• High resolution and sensitivity.
• Reduce footprint of analytical systems.
• Reduce sample contamination
Fabrication via photolithography
(a) Photolithography generation of the master:
(i) Deposition of photoresist on a silicon substrate.
(ii) Exposure to UV light through the photomask.
(iii) Post development, the UV-cured photoresist layer remains, whereas rest of
the layer is washed away.
 Fabrication via photolithography
(b) Preparation of the PDMS replica and bonding to a substrate:
(i) PDMS and cross-linker mixture is poured over the silicon substrate with photoresist.
(ii) The PDMS layer is thermally cured and pulled out from the silicon substrate.
(iii) Glass and PDMS are exposed to plasma and surface bonded, producing the PDMS-glass
microchannel.
Materials
• Semiconductor(silicon): cannot withstand high voltage and
are not compatible with optical detection technology,
• Glass: good electroosmotic and optical properties
( the perfect microfluidic chip system)
-not easy to photolithography
- Complex process - Waste time - High cost
• Polymer materials: simple processing, cheap raw materials,
good insulation, high pressure resistance, thermal stability,
biocompatibility, gas permeability, and low elastic modulus.
E.g. Polydimethylsiloxane (PDMS) are currently
a popular material for microfluidic chip fabrication.
Microarray
What is microarray?
Binding an array of thousands
to millions of known nucleic acid
fragments to a solid surface,
Application
Aid in the identification of new
genes, as well as in studying
their function and expressions
in different conditions.
How to make microarray

•Photolithography
•Mechanical microspotting
•Inkjet printing
 Photolithography
In situ synthesis (e.g.Affymetrix GeneChip arrays): use light to create pattern , to produce
DNA/RNA microarray.
1. Substrate is covalently modified with a silane reagent to obtain a surface containing reactive.
2.Amine groups are modified with a specific photo protecting group
3.The surface of the specific regions are activated through exposure to light,
4.A single base is added to the hydroxyl groups of these exposed surface regions.
5..The process of photoprotection and nucleotide addition is repeated until the desired sequences
are generated.
 Photolithography
This process is used to synthesize oligonucleotides, the number of
steps is determined by the length of oligos, not their number, since
many different sites could be synthesized simultaneously.
Each probe on the chip requires 4 masks per round
of synthesis: one mask to allow addition of the
required base and three other masks to prevent light from
deprotecting the same spot while the other
three nucleotides are being added.
On average, each probe is 25 nucleotides long,
requiring about 100 masks per chip.
 Mechanical microspotting
Uses direct contact of computer-controlled multiple pins,
tweezers, to deliverpicoliter volumes of
pre-made biochemical reagents
(e.g., oligonucleotides, cDNA,
genomic DNA, antibodies) to
a solid surface.
Inkjet printing
Spotted DNA Microarrays:
the sample is taken from the source plate, and a droplet of the
sample is ejected from the print head onto the surface of the
substrate. Similar to microspotting
Avoiding direct surface contact but cannot be used to produce
microarrays as dense as those prepared by photolithography or
microspotting approaches.
Materials
• Types:
• In the early phase, polyvinylidene fluoride (PVDF) acted as substrate
• After few years ago, glass, polymer, plastic, nitrocellulose, porous gel
sheet and silicon sheet have been applied.
• Chemical treatment
• The surface of original substrate lacks the active functional groups which
are necessary for immobilize
biomolecules （ e.g.DNA 、 antibody 、 protein 、 aptamer,
polysaccharides ） and it also has a high level of non-specific
biomolecular to attach
• According to specific application, substrates needed to be processed by
different kinks of chemical treatments
Thank You