biosensors, afinity based detection, transducer, cmos, cmos fabrication process, electrochemical transducer, analyte

1. Gookyi Dennis A. N.
SoC Design Lab.
BIOSENSOR SYSTEM IN
STANDARD CMOS
PROCESSES: FACT OR
FICTION?
BYUNGCHUL JANG,STUDENT MEMBER, IEEE,
AND
ARJANG HASSIBI, MEMBER, IEEE
June.05.2014

2. 2
Contents
• Introduction
• Biosensor Systems
• CMOS Fabrication Process
• Integrated Biosensors
• Conclusion

3. 3
Introduction: Affinity-Based Detection
• Affinity-Based detection as opposed to catalytic based
detection is a fundamental method in identifying and
measuring the abundance of biological and biochemical
analytes.
• As show below, in Affinity-Based detection, biological
analytes are specifically bound to immobilized capture
probes.
• The main aim of this detection platform is to produce
detectable signals based on the captured analytes
• The generated signal is directly proportion to the amount
of the target analyte in the sample.

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Introduction: Challenges
• Analyte motion in biosensor settings is mainly due to diffusion
which from a microscopic point of view is a probalistic mass-transfer
process.
• This makes the analyte collision with the probes a probalistic
process.
• When the concentration of nonspecific species becomes higher than
that of the target analyte, nonspecific binding may dominate the
measured signal.
• This limits the minimum detectable level (MDL)
• These uncertainties lowers the accuracy of biosensors which does
not satisfy the requirements of many high performance
biotechnological applications.
• In addition, biosensors are not fully portable devices because their
detection platform consist of fluidic system and bulky detectors.

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Introduction: Proposed Solution
• A proposed solution is to use semiconductor fabrication
technologies to build compact, high performance and cost-
efficient biosensor systems.
• Such system will include both the fluidic system and the
sample preparation process and the transduction process.
• The sample preparation processes in recent years have been
addressed in the form of microfluidic and has automated the
liquid handling systems.
• The integration of the detection and the read out circuitry
have not been addressed as of yet
• This is because of the technical challenges of manufacturing
transducers using custom surface and bulk MEMS procedures,
and also the performance and cost justification of monolithic
integration of all components.

6. 6
Introduction: CMOS Solution
• CMOS fabrication processes, which is the most robust and
widely used fabrication processes in semiconductor industry
for biosensors has emerged
• CMOS beats MEMS in terms of yield, cost-efficiency and
integration capabilities
• From an electronic design point of view, CMOS offer huge
degree of flexibility and system level integration

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Biosensor Systems
• Different functional blocks are integrated to measure analyte
specific signals in biosensors
• As shown below, biosensors not only consist of biochemical
systems but also electronic components
• The fundamental functional blocks in all biosensors include the
assay and the transducer
• This is because these components are necessary for the
functionality of the whole system

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Biosensor Systems: Assay
• The assay in all affinity-based biosensors is a technique
used to facilitate binding of probe-target complexes to
produce a detectable signal which indicates the presence
of the targets and its amount in the sample
• Components required for affinity-based detection includes
molecular recognition layer and a transducer

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Biosensor Systems: Assay
• Biosensors functions in solutions that comprised the target analytes
in addition to different biological and chemical molecules.
• The assaying procedure, may include label based detection
• Label-based detection is cumbersome and therefore efforts have
been made to detect target molecules using only their intrinsic
properties such as charge and mass
• Independent of the detection techniques, all measurements in
biosensor systems are counting processes

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Biosensor Systems: Transducers
• To count the number of captured analytes, different
transducers can be used
• A transducer is a device that converts from one type of
energy to another
• The categories of transducers depend on the kind of
signal or parameter the biosensor system creates or
alters

11. Biosensor Systems: Transducers
• Electrochemical transducers exploit analyte capturing to
change the electrochemical characteristics of electrode
electrolyte systems.
• Mechanical transducers: an electromechanical parameter of
the system is changed by the additional mass of the captured
analytes.
• Optical transducers: create or selectively absorb certain
wavelength of light based on the captured analytes.
• Thermal transducers: measure the temperature change during
biological thermal reaction to detect the total number of
molecules involved in the reaction
11

12. 12
CMOS Fabrication Process: Anatomy of
CMOS Integrated Systems
• CMOS fabrication technology is widely used in
microprocessors, microcontrollers and other digital logic
circuits
• Difference between CMOS and other fabrication processes
such as bipolar can clearly be seen in the structure of their
active devices
• The active devices in CMOS include p-type and n-type
MOSFETs

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CMOS Fabrication Process: Anatomy of
CMOS Integrated Systems
• To electrically access the transistors and create a certain
circuit topology, multiple interconnect metals are fabricated
in the process
• These interconnect metals can be connected together and to
the transistor

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CMOS Fabrication Process: Transducers in CMOS
• To implement biosensors in CMOS, we need to identify which
components can be fabricated using the process
• The interface circuitry, data converters and DSP blocks are all
electronic circuits and can be integrated in CMOS
• Building of transducers in CMOS is not as flexible as electronic
components because CMOS is optimized for digital circuits and not
so much for sensors
• Nonetheless, we can build transducers in CMOS and use them to
design high performance sensors

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Transducers in CMOS: Electrochemical
Transducers
• Consist of electrodes where electrons are charge carriers
and electrolyte where ions are charge carriers
• The transducers extract information from the electrical
characteristics of the electrode-electrolyte systems
• Some of the characteristics include: potential, current,
impedance and I-V curves
• The main challenge is to create the system to connect
the electrode to the chip
• The only metal available in CMOS which can be exposed
the electrolyte is made up of aluminum which has
impurities
• A solution to this is to use post-fabrication processes to
create more robust electrode on top of the metal

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CMOS Fabrication Process: Interface and
Packaging
• In standard IC package has CMOS chip electrically connected
to the pins of the package
• In general, signals can be coupled into CMOS ICs either
from the top or from the bottom of the chip

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Integrated Biosensors
• In contrast to conventional biosensors where incubation
and detection are carried out independently, integrated
biosensors detect binding without separate hybridization
and detection processes
• The feasibility of combining those processes on a single
platform allows integrated biosensors to detect binding
in real time

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Integrated Biosensors
• An example of an integrated biosensors is shown below:
• The detectors are integrated using CMOS and each
capturing spot has its own read out circuitry
• The figure above also shows an integrated fluorescence
biosensor
• Photo detectors are fabricated using standard CMOS
• Emission filter and FOF are integrated to the top surface
of the biosensor chip using post fabrication processes

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Conclusion
• Recently, there have been trends to implement CMOS as a the
backbone fabrication method for biosensors
• Although CMOS is optimized for digital electronics, it still can
be used to realize transducers, readout circuitry and digital
signal processing blocks used in biosensors
• The challenge is essentially the interface design which couples
the assay to the IC chip
• This may require additional post fabrication processes