Background
CMOS foundries backed by several trillion dollars of funding have established themselves as efficient mass-production platforms that lowered the cost of microelectronic devices significantly. Since their inception, the advancements in CMOS technology have enabled industries to significantly lower costs of microelectronic devices to the extent that they're affordable to customers.
Today's foundry processes have reached the threshold of 15nm and facilitate the manufacturing of highly dense systems with millions of active elements such as Ion-Selective-Field-Effect-Transistors (ISFET).
These advancements in technology coupled with the low cost and highly integrated sensors and circuits, CMOS devices have set a new frontier and found highly varied applications in the field of Life Sciences.
CMOS compatible silicon nanowires configured as field-effect transistor (Si NW-FETs) have shown notable precedence for real-time, label-free and highly sensitive detection of a wide range of biomolecules. The ability to detect very low concentrations of small molecules such as proteins and DNA at a low cost has tremendous applications for medicine and basic biochemistry. Most standard techniques rely on optical characterization methods which involve tagging the analyte of interest with a fluorescent molecule, this approach has plenty of limitations and fundamental constraints.
Biosensors
The term "biosensor" is short for "biological sensor". This device is made of a transducer and a biological element that may be an enzyme, an antibody or a nucleic acid. The biological element interacts with the analyte being tested and the biological response is converted into an electrical signal by the transducer. Depending on their application, biosensors are also known as immunosensors, optrodes, resonant mirrors, chemical canaries, biochips, glucometers and biocomputers.
Every biosensor comprises of: Biological component that acts as the sensor, an electronic component that detects and transmits the signal.
CMOS Applications:
Laboratory-on-chip (LoC) is a multidisciplinary approach that can be deployed for miniaturization, integration and automation of biological assays. Biology and chemistry are experimental sciences that continue to evolve and develop new protocols. Each protocol contains step-by-step laboratory instructions, lists of necessary equipment and required supplies. The engineering aspect of LoC design aims to embed all these components into a single chip for specific applications. Several clear benefits of this technology over traditional methods, including portability, full automation, ease of operation, low sample consumption, fast assays time, make LoCs suitable for highly throughput screening, early detection of disease, point-of-care care testing, and environmental assessment.
Standard complementary metal-oxide semiconductors technology, by offering a distinct cost, integrated circuits (ICs) and embedded sensors and/or actuators, as such, is a good fit for implementation of some of the essential functions of LoCs. Indeed, microelectronics CMOS technology allows the fabrication of an active substrate with different types of sensing or actuating sites that can be addressed in a random access mode by means of decoders.
Photodiodes, ion-selected field-effect transistors (ISFETs), lateral/substrate bipolar transistors and microelectrodes, realized in the topmost metal layer are the front-end devices in the CMOS process, which can be employed for optical sensing, electrical charge detection, temperature measurement and electrochemical sensing respectively. In addition to this, the topmost layer can be patterned in a way that realizes dielectrophoresis microelectrodes or magnetic micro coils for cellular manipulation.
Among several microelectronic devices that are employed for LoCs, CMOS capacitive biointerfaces have received significant interest for several applications, including DNA detection, antibody-antigen recognition, and bacteria sensing.
Figure: CMOS capacitive sensor consisting of IC, sensing electrodes and functionalized sensing layer
A look at Commercial Applications of CMOS Biosensors: Biosensor Chip against infectious diseases
The following recent innovation merely illustrates the potential and capabilities of the CMOS biosensor chips and serves to illustrate the versatility of CMOS. CMOS process technology has established itself as the bedrock of modern integrated circuit technology.
In May 2020, Roswell Biotechnologies and imec announced a partnership to develop the first commercially available molecular electronics biosensor chips.
"The urgent need for a new generation of rapid, low-cost, consumer surveillance and diagnostics tools has been made extremely clear in the current COVID-19 pandemic," said Roswell President & CEO Paul Mola. "In that area, the Roswell molecular electronic platform will transform the way infectious diseases are detected, with powerful new capabilities that enable, rapid screening of many infectious diseases at once, or many viral strains, with portable or handheld devices."
Molecular electronic sensor chips integrate single molecules as electrical sensor elements on standard semiconductor chips, making electronic biosensor devices massively scalable. The Roswell molecular electronic sensors represent an entirely new class of sensors, specifically designed to be maximally compatible with modern CMOS chip technology, delivering a technological breakthrough that significantly increases performance and lowers cost. This advance allows low-cost, high speed biomedical tests, including DNA sequencing and other forms of biomarkers sensing essential to modern medical diagnostics, to be deployed on simple portable handheld devices.
References: 1) CMOS Bio-Microsystems by Krzysztof Iniewski.
-Ishika Mahajan
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