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

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Contents•I

ntroduction•B

iosensor Systems•C

MOS Fabrication Process•I

ntegrated Biosensors•C

onclusion

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Introduction: Affinity-Based Detection•A

ffinity-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•A

nalyte 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.

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Introduction: CMOS Solution•C

MOS 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•D

ifferent 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•T

he 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

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

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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•A

n 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•R

ecently, 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