The Next Big Thing In Science Is Really, Really Small.
Nanosensors 101: the basics of what they are, how they work, and how we build them all in one place.
“There is plenty of room at the bottom.” — Richard P. Feynman, an American theoretical physicist and Nobel Prize winner. Feynman believed in 1959 that it could be possible to directly manipulate individual atoms. He suggested that these atoms assembled could be swallowed and used as tiny surgical robots.
And he was right. Today in the field of nanotechnology scientists are building nano-sized sensors to detect changes in the environment, allowing us to get closer to swallowing a pill and unleashing millions of tiny surgical robot-like sensors into our bodies to find diseases.
What Is A Sensor?
We use sensors all the time — to keep your home the temperature you want, to detect smoke indoors, the much coveted ‘clap on’ sensor that turns your lights on with the mere sound of a hand clap. A sensor is an instrument that responds to physical stimulus such as heat, light, sound, pressure, magnetism, or motion and sends the information to other electronics, frequently a computer processor. Sensors are created with one of these stimuli in mind and when the stimuli is present sensors measure and send a signal, which can automate an action.
What Is A Nanosensor?
A nanosensor is a microscopic sensor that is so small it can travel through your bloodstream inside of a cell. Nanosensors are measured using a nanoscale of measurement, which refers to anything that is 1–100 nanometers. One nanometer is equivalent to a billionth of a meter.
Materials at nanoscale have different properties than their equivalent “normal size” material. “Normal size” water boils at 100 degrees Celsius, but a drop of water with a 5 nanometer diameter boils at 95.9 degrees Celsius. Other materials like gold and silver go from a more malleable state in their “normal size” to a stronger, harder to bend state at their nanosize.
Why Size Matters
Nanosensors are extremely powerful because they can measure things at a scale other sensors can’t and have extreme sensitivity due to their small scale. Thanks to their microscopic size they only need a microscopic sample size to get a reading. Think of them as a teeny, tiny canaries in a coal mine; alerting us whenever a shift in the environment has taken place. The smaller the system, the more efficient and fast it is. Due to their microscopic size, nanosensors are super-efficient and provide real time monitoring.
For an example, current MRI technology identifies cancer in the form of tumors or large cellular masses, but a nanosensor can detect the presence of a cancer causing protein in a cell. This shift from monitoring cell masses to monitoring for the first sign of a protein created, could be the difference in a stage 1 treatment vs a stage 4 treatment plan; vastly affecting the chance of patient survival.
Advantages of Nanosensors
· Higher accuracy
· Increased data density
· Faster, real time monitoring
· Better signal to noise ratio
· Little impact to phenomenon being measured
What Can Nanosensors Detect?
Nanosensors can sense and detect biological, chemical, and physical signals at a microscopic level; which means they can report on changes in volume, concentration, dislocations, displacement, and temperature in small systems like cells, genes, viruses, etc.
Examples of what they can detect:
· Various chemicals in water for pollution monitoring or unsafe conditions like pesticides and heavy metals in river water
· Remote sensing of airborne pathogens during an epidemic, or before an outbreak
· Levels of toxic substances before and after bioremediation
· Measurement of folic acid, biotin, vitamin B12
· Toxic metabolites such as mycotoxins
· Bacteria identification in contaminated food
· Physical parameters such as temperature, displacement, flow or speed like in the case of accelerometers in Micro-Electro-Mechanical Systems (MEMS) devices like airbag sensors, microphones, tire pressure sensors, etc.
· Important medical diagnostic changes — quickly uncovering organ failure, contamination in the body, cancerous cells, glucose level
Electrical Signal Measurement Types
Nanosensors convert observations into data, which are sent through electrical signals. They are classified based on the form of electrical energy signal they detect: physical, chemical, or biological. However, there are many type of sensors within these three classifications, such as optical nanosensors and magnetic nanosensors. The particles nanosensors monitor are called analytes. The analyte will inform the mechanism for measurement, which then determines the type of nanosensor needed.
Physical/Mechanical nanosensors measure environmental changes like temperature, pressure, flow, stress, strain, position, displacement, force, acceleration, mass, volume, and density. Physical/mechanical nanosensors change their electrical conductivity when the material is physically manipulated and this physical change invokes a detectable response.
Use case example: In order for a specific treatment to be successful we need to administer it when a cell is at an exact temperature. Using a physical internal nanosensor we can monitor when the cells are at the temperature to administer treatment for maximum success.
Chemical nanosensors monitor molecular, composition, and concentration of electrical conductivity changes. Most nanomaterials have a high electrical conductivity, which reduce upon binding or absorption of a molecule. This detectable change is then measured.
Use case example: We need to ensure there isn’t any lead in the water from the older pipes supplying drinking water to an elementary school. Using a chemical nanosensor we are notified when there are trace amounts of lead leaking into the water supply and immediately stop students from drinking the water.
Biological nanosensor monitors detect biological changes in proteins, antigens, and DNA strands (nucleic acids). When an analyte connects to a biological receptor (like a key and lock) a detectable change is then measured.
Use case example: When there is a presence of a specific protein that we know is a cancer biomarker, then a disease is present. Using a biological nanosensor we can quickly identify the protein’s presence before the disease spreads beyond treatment or repair.
Measurement Process
In order for the nanosensor process to begin we need the presence of the analyte [the particle(s) we’re trying to measure] or physical change to occur. Once the analyte is present or physical change happens, the nanosensor will react. If no analyte presents or physical occurs, then the nanosensor will not activate. These are the core components of a nanosensor:
1. Receptor (can be chemical, physical, or biological) — reacts to the environmental change
2. Electrical Interface — produces a signal
3. Signal amplifier — transmits the signal to the processor
4. Signal processor — computer software
5. Display — translation to human interface
Nanostructures
There are many types of nanostructures that can be used for nanosensors. These are some of the more popular types of nanosensor structures:
Biosensors. A biosensor is an analytical device that converts a biological response into a quantifiable and processable signal. They take the shape of biological structures that currently exist in nature.
What sample do we have and what particles are we planning to monitor? The answers to these questions will determine the type of bioreceptor that will specifically bind to the analyte, therefor producing a signal. Once the bioreceptor is chosen the transducer is selected. A transducer signal (which could be anything from the in-coupling angle of a laser beam to the current produced at an electrode) is converted to an electronic signal and amplified by a detector circuit using the appropriate reference and for processing by computer software that converts into data a human operator would understand.
Cantilevers. A cantilever-based sensor has multiple cantilevers which look like rows of tiny diving boards, with carefully balanced molecules on them. When there is a change in the environment the cantilever bends and sends a signal of change (aka presence of the analyte). Cantilevers will bend when there is a heat source, changes in surface tension, or magnetic pull. This triggers the transducer to send an electronic signal to the signal conditioning circuit which sends an electrical signal used for processing by computer software that converts it to data a human operator would understand.
Nanotubes. A nanotube sensor contains a multitude of carbon atoms arranged in hexagons in the shape of a tube. They act as transistors and pairs of nanotubes can act as logic structures. They have been added to golf balls, tennis rackets, and other materials to increase strength.
Buckministerfulleren C60, aka Buckyballs. A buckyball sensor consists of 60 atoms of carbon arranged in hexagons in the shape of a ball. They were created by vaporizing carbon. They can be used for reinforcement, adding strength to substances, and for drug release in buckysomes (buckyballs + liposomes).
Nanowires. A nanowire sensor is an extremely thin wire with a diameter on the order of a few nanometers. Germanium and silicon nanowires can be made and are used for lithographic printing and silicon chips. In 2007, orderly arrays of nanowires were grown on crystals with a technique that could lead to high density memory chips and transparent LEDS. Nanowires conductivity changes when it binds to cancer proteins, allowing for detection of cancer.
Sensor Standards
What qualities does a nanosensor posses in order to be used?
· Accurate, precise, reproducible results
· Free from electrical noise
· Structural stability
· Sensitivity to analyte
· Cheap, small, portable, and capable of being used by a semi-skilled operator
· Reaction should be independent from physical parameters when not measuring for physical environment (i.e. stirring, pH, and temperature)
How Nanosensors Are Made (Nanofabrication)
Nanosensors are made through a process called nanofabrication; the design and construction of nanometer-sized objects. There are two main types of nanofabrication: top down lithography and bottom up assembly.
Top Down Lithography
Starts with a pattern generated on a larger scale which is then reduced to nanoscale. Lithography is a process that uses focused radiant energy to create precise temporary patterns in silicon wafers and other materials that have been coated on a substrate.
Typically, an oxidized wafer is coated with a photoresist (light sensitive) layer. The process consists of starting with a large piece of material and dwindling it down. Light is used to transfer a geometric pattern from a photomask to the photoresist; essentially using the photomask as a stencil. After UV exposure the photoresist undergoes a photochemical reaction. When the wafer is rinsed in a developing solution, like film, there is a clear outline of the mask and the exposed areas are removed. A series of chemical treatments engraves the exposure pattern into, or enables deposition of a new material onto the desired pattern upon the remaining material.
There are four major processes that need to happen:
1. Lithography — process of printing from a flat surface treated so as to repel the ink except where it is required for printing
2. Etching
3. Deposition — action of depositing
4. Doping — add an impurity to produce a desired electrical characterstic
…and possibly repeat.
The most used approach is photolithography (optical lithography or UV lithography), which is used to pattern parts of a thin film or the bulk of substrate. It’s often applied to semiconductors manufacturing of microchips.
Pros:
· It’s the fastest method currently
· Large production ability
· Currently being used in electrical applications.
Cons:
· Actual implementation is very complex
· Very expensive
· Needs to be precise
· Wasteful
· Requires a flat substrate and is not effective at creating other non-flat shapes
· Requires extremely clean operating conditions
· Requires an optical mask
· Becomes less accurate as the size gets smaller than 100nm
Bottom Up Assembly
Begins with the atoms or molecules and builds up to nanostructures. It’s a process of starting with the smallest possible parts of a structure and using them to build a larger, ordered structure. There are two types of bottom up assembly methods: self-assembly (outside forces) and molecular assembly. Self-assembly is a theoretical concept by which outside forces create nanofactories that use atoms to form structures that resemble gears and other nanorobots in perpetual motion building molecular structures. Want to see what it could look like? Check it out here.
Molecular bottom up assembly is a process that naturally occurs in living organisms. Molecular assembly is the coordinated action of independent entities to produce larger, order structures, or to achieve a desired shape at the atomic scale. We see this self-organizing process commonly in nature at the molecular level (i.e. protein folding and cells) to the planetary scale (i.e. weather systems) and beyond (i.e. galaxies). Chemical bonds define the physical structure; the angle of the bonds formed create the structure. Strong interactions at the chemical level will define some assembly, including: covalent bonds (sharing of electrons between atoms) and ionic bonds (transfer of electrons).
Within self-assembly there are two major techniques. The first, colloidal has exciting possibilities in terms of generating novel materials by combining nanoparticles with different properties into well-defined crystalline structures. The second is DNA, which is the archetypal self-assembling system. For more information on DNA self-assembly structures (like DNA origami) check out “What Is Nanofabrication” by nanowerk.
Pros:
· More efficient
· Less expensive
· Amazing use cases for chemical and biological purposes
· High reproducibility
· Less waste
Cons:
· Takes longer to build
· Lack of understanding of complex biological structures
· Contamination on devices
· Requires a nano-sized factory with nano-sized robotic components that do not currently exist (assisted assembly)
· Constant and consistent energy source at the nanoscale
· Due to particle structure sometimes no structure will occur
· Fabrication of robust structures is difficult
Directed Self Assembly
This is a combination of both the top down and bottom up methods. Using the boundaries/templates created by top down methods in collaboration with the local interactions built into the molecular structure of the material (bottom up).
Overall Fabrication Drawbacks
Nanofabrication is a developing science and as such has a high cost, is prone to error, and will have future unforeseen challenges. Besides the cons previously listed, most nanofabrications aren’t compatible with current the electronic industry’s current use for amplifiers and signal processing, which means that even if a nanosensor was fabricated, monitored a change, and sent a signal there will be no way of communicating it to the macro world.
How To Improve
Engineers, researchers, scientists, students, and companies are doing extensive research to figure out how to resolve these critical issues.
It’s possible that we could see nanofabrication improve by:
· Focusing on advancing the nanoamplication system and signal processing components. Can other molecules and structures in the environment turn into conductors, creating a massive game of telephone?
· Increasing community collaboration within the sciences across different fields of expertise. Just as the nanosensors are complex and made up of many parts, the team creating them should be just as diverse.It will take a group of diverse experts in the fields of mechanical engineering, molecular biology, computer modeling, chemists, and more to increase the speed of building successful nanosensors.
· Simulating new structures using software with molecular modeling and machine learning. This would allow us to better understand the building blocks of all living organisms and their complexities. Running different hypothetical models faster could virtually test new structures faster, cheaper, and more efficiently.
· Testing the bottom up molecular assembly method in different physical environments could lead to new approaches. Changing the temperature or magnetic field may affect the properties of the molecules and atoms, which would affect how they assemble with each other. These new environments may speed up the process of molecular self-assembly.
· Using structures found in nature that we have a deeper understanding of to create nanosensors, such as DNA. Using current knowledge of DNA structures, specifically a scaffold strand formation and hundreds of short staple strands for the assembly of three dimensional DNA origami objects. These structures mirror the size of virus capsids and have already gained interest as nanocontainers for drug delivery. Since they can be programmed to carry out specific tasks (i.e. transporting molecules and releasing them at a target site), these assemblies could act like a nanorobotic system.
Sources (Thanks, Google Search Bar!) and Continuing Education:
https://www.youtube.com/watch?v=Q9RiB_o7Szs
· https://www.azonano.com/article.aspx?ArticleID=1840
http://uotechnology.edu.iq/dep-materials/lecture/thirdclass/Nanotechnology2.pdf
http://uotechnology.edu.iq/dep-materials/lecture/thirdclass/Nanotechnology2.pdf
