In a bid to develop synthetic molecules and materials that are capable of mimicking biological recognition and function, intensive research in the fields of synthetic receptor technologies, smart materials, synthetic biology and smart indicators has been under way for the past 20-30 years. The development of synthetic receptors continues to grow rapidly. Novel molecular architectures, with ever improving selective binding properties are constantly being described, and in some cases providing much-needed physical insights into the nature of non-covalent interactions and molecular recognition. Such receptor systems are finding increasingly esoteric applications and this book captures the key developments at the synthetic receptor/biology/detection science interface.
The editor has extensive experience in applying smart materials and synthetic receptors to the development of biosensors. Reddy has developed smart, permselective and biocompatible molecularly imprinted polymers and membrane materials for the sensor/sample interface and the advancement of smart materials-based electrochemical, quartz crystal and optical sensors for medical, food and environmental applications.
Chapters demonstrate how growing disciplines such as biomimetics, synthetic receptor technologies, pattern recognition and nanotechnology are being used to develop new smart materials for diagnostic sensor and biosensor applications. Postgraduate students and researchers in academia and industry will benefit from this resourceful handbook.
About the Author
Dr. Sub Reddy (C.Chem. MRSC) obtained his first class degree in Chemistry from the University of Manchester. He received his Ph.D. in Membrane-based Electrochemical Biosensing from the same University (1996). His post-doctoral research interests have included the development of quartz crystal-based biosensors, operating in the liquid phase (University of Wales, Bangor; 1994-1997) and the development of application-specific odour sensors (UMIST, Manchester; 1997-1998).
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Advanced Synthetic Materials in Detection Science
By Subrayal Reddy
The Royal Society of ChemistryCopyright © 2014 The Royal Society of Chemistry
All rights reserved.
Biomimicry and Materials in Medicine
LARISA-EMILIA CHERAN, ALIN CHERAN AND MICHAEL THOMPSON
Past generations have attempted to tame, harness and conquer nature, and bring her to her knees. Such efforts have transformed over the years into a wiser, enthusiastic pursuit to unravel her secrets and copy the "engineering" afforded by nature. Implicit in this is the recognition that literally billions of years of evolution have resulted in the refining of biological structures at the macro- and nano-scales.
A living cell that grows and multiplies looks much like a robot that has learned to build itself. We are still not sure exactly how this machine was first assembled and programmed. In comparison, strident announcements with respect to scientists "creating life" in the lab are only lame self-promoting marketing strategies. The reality is that there is a failure to acknowledge the fact that the inception of such efforts were initiated with existing living cells before any major manipulations were made inside the cells. There is no clear definition of life; we even struggle to ascertain the difference between a living cell and a dead one. All the chemicals and physical properties are essentially identical, with the most remarkable feature being the inefiable force that controls those 100 000 chemical reactions in each second, in each living cell. For that matter, we are required to recognize that we do not even have a real definition of reality, only hypotheses which contradict the Copenhagen interpretation because of the need of an observer, explicitly the multiverse theory, Bohm's implicate order, Everett's parallel universes, and orchestrated quantum coherence. Troublesome as it is, we do not have a definition of time either, since the vibrations of the cesium atoms and quartz crystals only measure something that does not exist when we dream, for example; something that expands exasperatedly when we are bored and contracts when we are in the flow.
Leaving such big questions under the rug of modern science, where they belong, we turn to the somewhat more uncomplicated quest of mimicking nature by creating synthetic materials capable of both detecting biochemical and biophysical changes at the molecular level that reflect sensory mechanisms. Additionally, synthetic materials can replace natural biological components for medical corrective procedures and/or healing. Such activities are often characterized as being incorporated in the relatively new field of "biomimicry", a word coined by Schmitt some years ago.
1.2 Advanced Synthetic Materials
New materials which have features that can be modified under specific conditions are pushing forward the frontiers of scientific and technological capabilities. Synthetic materials designed to change their size or shape when exposed to heat, change from a liquid to a solid in magnetic fields, or dramatically change their volume, viscosity, conductivity, work function, etc., will allow new and interesting applications to emerge, not only for sensing and detection purposes, but also for everyday use. Smart materials with piezoelectric, magneto-rheostatic, electro-rheostatic, and memory hysteresis are already used in cars, coffee pots, glasses, or in space missions. Relevant to this chapter, intelligent biomaterials that respond to biological signals show great promise in regenerative medicine, diagnostics, and drug delivery.
Common examples include piezoelectric materials which produce a charge under mechanical stress and, conversely, contact or expand when a voltage is applied. In shape-memory alloys and polymers, large deformations can be induced and recovered by temperature changes or stress changes. This pseudoelasticity is the result of martensitic phase changes. In magnetostrictive materials, changes in shape can be instigated by magnetic fields; on the other hand, these materials also exhibit changes in magnetization under mechanical stress. Magnetic-shape memory alloys change their shape when under a magnetic field, and pH-sensitive polymers change in volume when exposed to alterations in the pH of the solution in which they are immersed. Halochromic materials change their color as a result of change in acidity; they are very suitable detection materials for applications such as corrosion detection. Chromogenic materials change color as a response to electrical, thermal, or optical changes. When an electric voltage is applied, electrochromic materials change their color or opacity, as in liquid crystal displays. Thermochromic materials change in color depending on temperature changes and photochromic materials respond to light changes (used in light-sensitive sunglasses which darken when exposed to bright sunlight). Photomechanical materials change shape when exposed to light. Dielectric elastomers produce large strains under external electrical fields. Magnetocaloric materials change reversibly in temperature under a changing magnetic field. Thermoelectric materials convert temperature differences into electricity. Such active materials are ideal for sensor devices and for such applications as resorbable bioceramics, adaptive bioglasses, biomimetic polymers and gels, active nanoparticles, smart textiles, and active optical fibers. Manipulation of material properties at the atomic and molecular scale is leading to self-assembling materials, nanolithography, DNA-based technologies (such as DNA computing), nano- and micro-engineered devices for diagnostics, pharmaceuticals, therapies, drug delivery systems, biocompatible implants and prostheses, and bio-functional systems.
We now turn to the employment of new materials in a plethora of applications in biology and medicine.
1.2.1 Nitinol and Memory Metals
A shape memory transformation was first observed in 1932 in an alloy of gold and cadmium, and then later in brass in 1938. The shape memory effect was seen in the gold–cadmium alloy in 1951, but this was of little use. Some 10 years later, in 1962, an equiatomic alloy of titanium and nickel was found to exhibit a significant shape memory effect and Nitinol (so named because it is made from nickel and titanium and its properties were discovered at the Naval Ordinance Laboratories) has become the most common shape memory alloy (SMA). Other SMAs include those based on copper (in particular CuZnAl), NiAl, and FeMnSi, although it should be noted that the NiW alloy has by far the most superior properties.
Metal alloys of nickel and titanium have the remarkable properties of remembering the shape by undergoing a phase change in which atoms are shifting their position in response to a specific stimulus, such as temperature or stress. The phase change temperature can be tuned by varying the ratio of nickel to titanium. The resulting structure has a highly symmetrical cube structure called austenite at temperatures above the phase change temperature and a much less symmetrical structure at temperatures below the phase change temperature, called the martensite state. In the latter state the material is very elastic, but the austenite state is rigid. The modification of the crystal lattice during the transformation can be carefully controlled. The shape change may exhibit itself as either an expansion or contraction. The transformation temperature can be tuned to within a couple of degrees by changing the alloy composition. Nitinol can be made with a transformation temperature anywhere between -100 °C and +100 °C, which makes it very versatile.
The memory mechanism is based on the thermal energy acquired by the sample through heating, providing the energy necessary for the atoms to return to their original positions so the sample regains its original shape. Springs made of such alloys return to their original shape in warm water or in streams of hot air. Nitinol and superelastic materials made of shape memory alloys of gold–cadmium, copper–aluminum–nickel, copper–zinc–aluminum, and iron–manganese–silicon are used today in medical applications, aerospace, and the leisure industry, namely in vascular stents, for anchors attaching tendons to bones, medical guidewires, medical guidepins, root canal fillings, bendable surgical tools, cardiac catheters, orthodontic wires, flexible eyeglass frames, etc.
Still many years away is the use of SMAs as artificial muscles, i.e. simulating the expansion and contraction of human muscles. This process will utilize a piece of SMA wire in place of a muscle on the finger of a robotic hand. When it is heated, by passing an electrical current through it, the material expands and extends the joint; on cooling, the wire contracts again, flexing the finger. In reality this is incredibly difficult to achieve since complex software and surrounding systems are also required. NASA has been researching the use of SMA muscles in robots which walk, fly, and swim.
SMA tubes can be used as couplings for connecting two tubes. The coupling diameter is made slightly smaller than the tubes it is to join. The coupling is deformed such that it slips over the tube ends and the temperature changed to activate the memory. The coupling tube shrinks to hold the two ends together but can never fully transform so it exerts a constant force on the joined tubes.
In addition to the shape memory effect, SMAs are also known to be very flexible or superelastic, which arises from the structure of the martensite. This property of SMAs has also been exploited in mobile phone aerials, spectacle frames, and underwires in bras. The kink resistance of the wires makes them useful in percutaneous angioplasty, a surgical procedure requiring catheters which need to remain straight as they are passed through the body. Nitinol can be bent significantly further than stainless steel without suffering permanent deformation.
1.2.2 Smart Ceramics
Ceramics are more chemically stable and inert than metals. They can be classified into three distinct categories:
1. Oxides such alumina, beryllia, zirconia, and ceria
2. Non-oxides such as carbide, boride, nitride, and silicide
3. Composite materials such as particular reinforced fibers or combinations of oxides and non-oxides
Ceramics are used in numerous technical applications. Since ceramics are so much more biocompatible when used inside the human body, they play a major role as synthetic biomaterials that can be part of the systems which treat or replace a living tissue or lost function. Depending on the particular application, the major requirements beside biocompatibility are resistance to abrasion and wear, fatigue, strength, durability, and resistance to corrosion, especially when they are used as an implant material. The most common materials are alumina, zirconia, bioglass, hydroxyapatite, and tricalcium phosphate. Not only they are inert, but they are also resorbable. They can dissolve and integrate actively in physiological processes such as bone healing. Hydroxyapatite can be actually found in the human body, in teeth and bones. The synthetic material is commonly used as a filler to replace amputated bone or as a coating to promote bone ingrowth into prosthetic implants. Natural coral skeletons can be transformed into hydroxyapatite at high temperatures. Their porous structure encourages the rapid ingrowths of bones. The high-temperature treatment destroys any organic molecules such as proteins, thus preventing immune rejection.
Zirconia is used on the artificial femoral heads employed in hip replacements. It gives strength to the structure, so its dimensions can be smaller and less traumatic for the patient. It is also used in shoulder, knee, spinal implants, and phalangeal joints. In dentistry, it is used with increased frequency for crowns, bridges, and implant abutments. Crystal zirconia is a modern dental ceramic replacement for the metal substructures used under porcelain crowns and bridges. It is translucent, thus giving the overlaid porcelain a brighter and more natural look. It is biocompatible and, unlike amalgams and metal alloys, does not generate adverse reactions or allergies. It is virtually unbreakable, so the dental work can last for a lifetime.
Finally, a particularly interesting application of ceramic materials is their use in the treatment of cancer, through hyperthermia and radiotherapy. In the quest to avoid the devastating effects of chemotherapy, glass microspheres are inserted into the tumor using a catheter and the radiation is focused on the tumor, similar to brachytherapy for prostate cancer. This causes minimal damage to the surrounding tissue. It is a simple treatment that can be performed on an outpatient basis.
1.2.3 Smart Polymers
Smart polymers are used for industrial purposes, in medicine, sports, and agriculture due to their inert or bioactive properties. Biodegradability is also a great advantage of such polymers. High-performance polyethylene is used in medicine for total or partial joint replacement of hip, knee, or intervertebral implants due to its high impact strength given by extremely long chains. It is highly resistant to corrosion, has very low moisture absorption and a very low friction coefficient. It is self-lubricating and highly resistant to abrasion, more resistant than carbon steel.
Hydrogels, networks of hydrophilic polymer chains in colloidal gels, with water as the dispersion medium, are highly absorbent materials; they possess a high degree of flexibility, very similar to natural tissue, due to their significant water content. Smart gels contain fluids, usually water in a matrix of large, complex polymers. These polymers are unique in that they respond to stimuli in an advanced way. Types of stimuli that affect smart gels are physical and chemical factors. Temperature, light, electric forces, magnetic forces, and mechanical forces are types of physical interactions on the gel that will precipitate a reaction. Chemical stimuli are usually pH changes or solvent exchanges. The reaction of the smart gel is always an expansion or contraction within milliseconds upon stimulation. When a gel swells, it absorbs additional fluid into it. When it deflates, it expels this fluid out of its membrane. The expansion and contraction are usually caused by a change in the polymer; the stimulus alters the polymer by making it more or less hydrophilic. For example, a significant pH decrease will neutralize ions in the gel, precipitating the polymers to be less hydrophilic and causing the gel to contract.
The effects of such synthetic gels are greatly aided by using nanoparticles. While microparticles usually allow the gel to function properly, smaller particles at the nanoscale increase intended effects dramatically. A great example of this is in the use of ferromagnetic particles. Ferromagnets are tiny particles that act as little bar magnets; applying a magnetic field on a smart gel encourages the ferromagnets to move. This movement raises the temperature of the gel and consequently causes the gel to expand. While microparticles of iron still allow the gel to expand, nanoparticles make the gel more responsive to the magnetic field.
Gels are used as scaffolds in tissue engineering to support living cells for tissue repair, as coatings of wells for cell cultures. Smart hydrogels use their environmental sensitivity to detect changes in pH, temperature, or concentration. They are also used in drug delivery systems, as biosensors, contact lenses (silicone hydrogels), EEG and ECG electrodes, and for dressings used in the healing of burns or hard-to-heal wounds.
Applications of smart gels permeate into various fields, including both medical and industrial. The two main applications for smart gels are in artificial muscle fabrication and drug release. In drug release, a smart gel containing the desired water-soluble drug is injected into the patient. After receiving a certain stimulus (usually temperature or pH), a hydrogel will expand by allowing the water and salt in the blood to enter the gel. The drug will be released from the gel in the desired environment. This concept can be used to release drugs to attack tumors or aid specific areas of the body (i.e. eye drops for the eye). This concept is beneficial because the area, duration, and speed of the release can be better controlled with a smart gel. Nanoparticles will help this medical technology by increasing the effectiveness of the gel by increasing the surface area of its constituents.
Excerpted from Advanced Synthetic Materials in Detection Science by Subrayal Reddy. Copyright © 2014 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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Table of Contents
Biomimicry and Materials in Medicine; Biomimetic Materials and Surfaces in Detection; Hydrogel-based Molecularly Imprinted Polymers for Biological Detection; Nanoparticle Technologies in Detection Science; Smart Indicator Technologies for Chemical and Biochemical Detection; Supramolecular Chemistry: Calixpyrroles; Macrocyclics; Ion and molecularly selective electrodes; Application of Pattern Recognition Techniques in the Development of Electronic Tongues