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Cell CANARY (Cellular Analysis and Notification of Antigen Risks and Yields) is a recent technology that uses genetically engineered B cells to identify pathogens. [1] Existing pathogen detection technologies include the Integrated Biological Detection System and the Joint Chemical Agent Detector. [2]
In 2007, Benjamin Shapiro, Pamela Abshire, Elisabeth Smela, and Denis Wirtz were granted a patent entitled “Cell Canaries for Biochemical Pathogen Detection. They have successfully manipulated the sensors so that they are sensitive to exposure of certain dangers, such as explosive materials or biological pathogens. What sets CANARY apart from the other methods is that the system is quicker and has a lower number of false readings. [3] Existing pathogen detection methods required that a sample be packaged and sent to a lab where techniques such as mass spectrometry and Polymerase Chain Reaction ultimately provided a blueprint of the nucleotide sequences present in a sample. The pathogen was then determined based on a database of pathogen nucleotides on file. This often resulted in a large amount of false positives and false negatives due to the non-specific nature of nucleotide binding. These techniques also required time that is not feasible in imminent situations. [4]
Cell CANARY is one of the newest, fastest, and most viable approaches to pathogen detection in a sample. [5] It has the ability to detect pathogens in a variety of media, both liquid and air, at a fraction of the concentration that older methods required to produce a viable signal. CANARY uses the B cell, a form of white blood cell that forms the basis for natural human defense. [6] An array of these b-cells is attached to a chip. Genes for producing antibodies are naturally on in these b-cells, which allow antibodies to coat the exterior surface of the cells. The genes for coding antibodies are then up-regulated in these cells, which allows for greater antibody production and therefore more of the cell surface to be coated in antibodies. [7]
This engineering principle allows lower concentrations of antigen to be detected by the cells. Antigens can then bind to the antibodies, resulting in a few naturally occurring B-cell reactions. At the final step of these reactions, Ca2+ ions are released, and in the presence of aequorin, photons are emitted. Aequorin is a photoprotein that can be extracted from marine organisms such as luminescent fish. [8] The emitted photons can then be read by a chip, on which the array of modified B cells have been attached to, ultimately providing a readout of the pathogen(s) present.
A unique set of responses is exhibited after exposure to each individual pathogen. [9] Therefore, cells will react differently to the introduction of a specific pathogen, the specific nature in which the “canary” cells respond to the pathogen indicates the unique identity of the pathogen that has been introduced. The more responses of a cell to a pathogen that are measured the more precisely the pathogen can be identified. Finally, after determining the presence and identity of the pathogen, all infected people can be effectively treated. [10]
There still need improvements on specific aspects of this complicated process. Some of the challenges include "building circuits that can interact with the cells and transmit alerts about their condition", developing technology to control the position of the cells on the chip, keeping the cells viable once on the chip and creating a living environment that supports the cells but protects the sensitive parts of the sensor. [11] The implications of a faster pathogen detection technology are widespread. A patient would be able to visit a medical professional, provide a sample of blood or urine, and get an analysis within minutes. [12] No longer would the patient and doctor have to wait on lab results to determine the presence of foreign bodies. The military would be able to test air samples and water samples to discover threats immediately before dispatching. High profile and even regular office buildings could have these sensors in every corridor to proactively hunt out air-borne pathogens, leaving enough time for evacuation. [13] This goes back to the idea of “canary in a coal mine”, where the B cells act as the canary to sniff out danger ahead of time. [14]
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.
Immunology is a branch of biology and medicine that covers the study of immune systems in all organisms.
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable disease, is an illness resulting from an infection.
Biodefense refers to measures to restore biosecurity to a group of organisms who are, or may be, subject to biological threats or infectious diseases. Biodefense is frequently discussed in the context of biowar or bioterrorism, and is generally considered a military or emergency response term.
An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellular bacteria, protozoa, helminths, and fungi which could cause serious problems to the health of the host organism if not cleared from the body.
Electrophysiology is the branch of physiology that studies the electrical properties of biological cells and tissues. It involves measurements of voltage changes or electric current or manipulations on a wide variety of scales from single ion channel proteins to whole organs like the heart. In neuroscience, it includes measurements of the electrical activity of neurons, and, in particular, action potential activity. Recordings of large-scale electric signals from the nervous system, such as electroencephalography, may also be referred to as electrophysiological recordings. They are useful for electrodiagnosis and monitoring.
Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium Francisella tularensis. Symptoms may include fever, skin ulcers, and enlarged lymph nodes. Occasionally, a form that results in pneumonia or a throat infection may occur.
Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.
A biosensor is an analytical device, used for the detection of a chemical substance, that combines a biological component with a physicochemical detector. The sensitive biological element, e.g. tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, etc., is a biologically derived material or biomimetic component that interacts with, binds with, or recognizes the analyte under study. The biologically sensitive elements can also be created by biological engineering. The transducer or the detector element, which transforms one signal into another one, works in a physicochemical way: optical, piezoelectric, electrochemical, electrochemiluminescence etc., resulting from the interaction of the analyte with the biological element, to easily measure and quantify. The biosensor reader device connects with the associated electronics or signal processors that are primarily responsible for the display of the results in a user-friendly way. This sometimes accounts for the most expensive part of the sensor device, however it is possible to generate a user friendly display that includes transducer and sensitive element. The readers are usually custom-designed and manufactured to suit the different working principles of biosensors.
Nanosensors are nanoscale devices that measure physical quantities and convert these to signals that can be detected and analyzed. There are several ways proposed today to make nanosensors; these include top-down lithography, bottom-up assembly, and molecular self-assembly. There are different types of nanosensors in the market and in development for various applications, most notably in defense, environmental, and healthcare industries. These sensors share the same basic workflow: a selective binding of an analyte, signal generation from the interaction of the nanosensor with the bio-element, and processing of the signal into useful metrics.
In molecular biology, biochips are engineered substrates that can host large numbers of simultaneous biochemical reactions. One of the goals of biochip technology is to efficiently screen large numbers of biological analytes, with potential applications ranging from disease diagnosis to detection of bioterrorism agents. For example, digital microfluidic biochips are under investigation for applications in biomedical fields. In a digital microfluidic biochip, a group of (adjacent) cells in the microfluidic array can be configured to work as storage, functional operations, as well as for transporting fluid droplets dynamically.
In artificial intelligence, artificial immune systems (AIS) are a class of computationally intelligent, rule-based machine learning systems inspired by the principles and processes of the vertebrate immune system. The algorithms are typically modeled after the immune system's characteristics of learning and memory for use in problem-solving.
The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.
Polyclonal B cell response is a natural mode of immune response exhibited by the adaptive immune system of mammals. It ensures that a single antigen is recognized and attacked through its overlapping parts, called epitopes, by multiple clones of B cell.
Autonomous Detection Systems (ADS), also called biohazard detection systems or autonomous pathogen detection systems, are designed to monitor air or water in an environment and to detect the presence of airborne or waterborne chemicals, toxins, pathogens, or other biological agents capable of causing human illness or death. These systems monitor air or water continuously and send real-time alerts to appropriate authorities in the event of an act of bioterrorism or biological warfare.
Bioreporters are intact, living microbial cells that have been genetically engineered to produce a measurable signal in response to a specific chemical or physical agent in their environment. Bioreporters contain two essential genetic elements, a promoter gene and a reporter gene. The promoter gene is turned on (transcribed) when the target agent is present in the cell’s environment. The promoter gene in a normal bacterial cell is linked to other genes that are then likewise transcribed and then translated into proteins that help the cell in either combating or adapting to the agent to which it has been exposed. In the case of a bioreporter, these genes, or portions thereof, have been removed and replaced with a reporter gene. Consequently, turning on the promoter gene now causes the reporter gene to be turned on. Activation of the reporter gene leads to production of reporter proteins that ultimately generate some type of a detectable signal. Therefore, the presence of a signal indicates that the bioreporter has sensed a particular target agent in its environment.
Elizabeth Marie Nolan is an American chemist and associate professor at Massachusetts Institute of Technology.
Signs Of LIfe Detector (SOLID) is an analytical instrument under development to detect extraterrestrial life in the form of organic biosignatures obtained from a core drill during planetary exploration.
Pamela A. Abshire is an American engineer. She was elected a Fellow of the Institute of Electrical and Electronics Engineers in 2018 for her contributions to CMOS biosensors.
