Lab-on-a-chip

A lab-on-a-chip (LOC) is a device that integrates one or several laboratory functions on a single chip of only millimeters to a few square centimeters in size. LOCs deal with the handling of extremely small fluid volumes down to less than pico liters. Lab-on-a-chip devices are a subset of MEMS devices and often indicated by "Micro Total Analysis Systems" (µTAS) as well.

Microfluidics is a broader term that describes also mechanical flow control devices like pumps and valves or sensors like flowmeters and viscometers. However, strictly regarded "Lab-on-a-Chip" indicates generally the scaling of single or multiple lab processes down to chip-format, whereas "µTAS" is dedicated to the integration of the total sequence of lab processes to perform chemical analysis. The term "Lab-on-a-Chip" was introduced later on when it turned out that µTAS technologies were more widely applicable than only for analysis purposes.


Chip materials and fabrication technologies
The basis for most LOC fabrication processes is photolithography. Initially most processes were in silicon, as these well-developed technologies were directly derived from semiconductor fabrication. Because of demands for e.g. specific optical characteristics, bio- or chemical compatibility, lower production costs and faster prototyping, new processes have been developed such as glass, ceramics and metal etching, deposition and bonding, PDMS processing (e.g., soft lithography), thick-film- and stereolithography as well as fast replication methods via electroplating, injection molding and embossing. Furthermore the LOC field more and more exceeds the borders between lithography-based microsystem technology, nano technology and precision engineering.


Advantages of LOCs
LOCs may provide advantages, which are specific to their application. Typical advantages are:

1. low fluid volumes consumption (less waste, lower reagents costs and less required sample volumes for diagnostics)
2. faster analysis and response times due to short diffusion distances, fast heating, high surface to volume ratios, small heat capacities.
3. better process control because of a faster response of the system (e.g. thermal control for exothermic chemical reactions)
4. compactness of the systems due to integration of much functionality and small volumes
5. massive parallelization due to compactness, which allows high-throughput analysis
6. lower fabrication costs, allowing cost-effective disposable chips, fabricated in mass production
7. safer platform for chemical, radioactive or biological studies because of integration of functionality, smaller fluid volumes and stored energies

For the chips to be used in areas with limited resources, many challenges must be overcome. In developed nations, the most highly valued traits for diagnostic tools include speed, sensitivity, and specificity; but in countries where the healthcare infrastructure is less well developed, attributes such ease of use and shelf life must also be considered. The reagents that come with the chip, for example, must be designed so that they remain effective for months even if the chip is not kept in a climate-controlled environment. Chip designers must also keep cost, scalability, and recyclability in mind as they choose what materials and fabrication techniques to use.


One active area of LOC research involves ways to diagnose and manage HIV infections. Around 40 million people are infected with HIV in the world today, yet only 1.3 million of these people receive anti-retroviral treatment. Around 90% of people with HIV have never been tested for the disease. Measuring the number of CD4+ T lymphocytes in a person’s blood is an accurate way to determine if a person has HIV and to track the progress of an HIV infection. At the moment, flow cytometry is the gold standard for obtaining CD4 counts, but flow cytometry is a complicated technique that is not available in most developing areas because it requires trained technicians and expensive equipment.

LASER

Light amplification by stimulated emission of radiation (LASER or laser) is a mechanism for emitting electromagnetic radiation, typically light or visible light, via the process of stimulated emission. The emitted laser light is usually a spatially coherent, narrow low-divergence beam, that can be manipulated with lenses. In laser technology, "coherent light" denotes a light source that produces light of in-step waves of identical frequency, phase, and polarization.



Design


A laser consists of a gain medium inside a highly reflective optical cavity, as well as a means to supply energy to the gain medium. The gain medium is a material with properties that allow it to amplify light by stimulated emission. In its simplest form, a cavity consists of two mirrors arranged such that light bounces back and forth, each time passing through the gain medium. Typically one of the two mirrors, the output coupler, is partially transparent. The output laser beam is emitted through this mirror.


Light of a specific wavelength that passes through the gain medium is amplified (increases in power); the surrounding mirrors ensure that most of the light makes many passes through the gain medium, being amplified repeatedly. Part of the light that is between the mirrors (that is, within the cavity) passes through the partially transparent mirror and escapes as a beam of light.


The process of supplying the energy required for the amplification is called pumping. The energy is typically supplied as an electrical current or as light at a different wavelength. Such light may be provided by a flash lamp or perhaps another laser. Most practical lasers contain additional elements that affect properties such as the wavelength of the emitted light and the shape of the beam.




Types and operating principles
 
Gas lasers


Gas lasers using many gases have been built and used for many purposes.


The helium-neon laser (HeNe) emits at a variety of wavelengths and units operating at 633 nm are very common in education because of its low cost.


Carbon dioxide lasers can emit hundreds of kilowatts[14] at 9.6 µm and 10.6 µm, and are often used in industry for cutting and welding. The efficiency of a CO2 laser is over 10%.


Argon-ion lasers emit light in the range 351-528.7 nm. Depending on the optics and the laser tube a different number of lines is usable but the most commonly used lines are 458 nm, 488 nm and 514.5 nm.


A nitrogen transverse electrical discharge in gas at atmospheric pressure (TEA) laser is an inexpensive gas laser producing UV light at 337.1 nm.


Metal ion lasers are gas lasers that generate deep ultraviolet wavelengths. Helium-silver (HeAg) 224 nm and neon-copper (NeCu) 248 nm are two examples. These lasers have particularly narrow oscillation linewidths of less than 3 GHz (0.5 picometers),[16] making them candidates for use in fluorescence suppressed Raman spectroscopy



Chemical lasers


Chemical lasers are powered by a chemical reaction, and can achieve high powers in continuous operation. For example, in the Hydrogen fluoride laser (2700-2900 nm) and the Deuterium fluoride laser (3800 nm) the reaction is the combination of hydrogen or deuterium gas with combustion products of ethylene in nitrogen trifluoride. They were invented by George C. Pimentel



Excimer lasers


Excimer lasers are powered by a chemical reaction involving an excited dimer, or excimer, which is a short-lived dimeric or heterodimeric molecule formed from two species (atoms), at least one of which is in an excited electronic state. They typically produce ultraviolet light, and are used in semiconductor photolithography and in LASIK eye surgery. Commonly used excimer molecules include F2 (fluorine, emitting at 157 nm), and noble gas compounds (ArF [193 nm], KrCl [222 nm], KrF [248 nm], XeCl [308 nm], and XeF [351 nm]).



Solid-state lasers


Solid-state laser materials are commonly made by "doping" a crystalline solid host with ions that provide the required energy states. For example, the first working laser was a ruby laser, made from ruby (chromium-doped corundum). The population inversion is actually maintained in the "dopant", such as chromium or neodymium. Formally, the class of solid-state lasers includes also fiber laser, as the active medium (fiber) is in the solid state. Practically, in the scientific literature, solid-state laser usually means a laser with bulk active medium, while wave-guide lasers are caller fiber lasers.


"Semiconductor lasers" are also solid-state lasers, but in the customary laser terminology, "solid-state laser" excludes semiconductor lasers, which have their own name.


Neodymium is a common "dopant" in various solid-state laser crystals, including yttrium orthovanadate (Nd:YVO4), yttrium lithium fluoride (Nd:YLF) and yttrium aluminium garnet (Nd:YAG). All these lasers can produce high powers in the infrared spectrum at 1064 nm. They are used for cutting, welding and marking of metals and other materials, and also in spectroscopy and for pumping dye lasers. These lasers are also commonly frequency doubled, tripled or quadrupled to produce 532 nm (green, visible), 355 nm (UV) and 266 nm (UV) light when those wavelengths are needed.


Ytterbium, holmium, thulium, and erbium are other common "dopants" in solid-state lasers. Ytterbium is used in crystals such as Yb:YAG, Yb:KGW, Yb:KYW, Yb:SYS, Yb:BOYS, Yb:CaF2, typically operating around 1020-1050 nm. They are potentially very efficient and high powered due to a small quantum defect. Extremely high powers in ultrashort pulses can be achieved with Yb:YAG. Holmium-doped YAG crystals emit at 2097 nm and form an efficient laser operating at infrared wavelengths strongly absorbed by water-bearing tissues. The Ho-YAG is usually operated in a pulsed mode, and passed through optical fiber surgical devices to resurface joints, remove rot from teeth, vaporize cancers, and pulverize kidney and gall stones.


Titanium-doped sapphire (Ti:sapphire) produces a highly tunable infrared laser, commonly used for spectroscopy as well as the most common ultrashort pulse laser.


Thermal limitations in solid-state lasers arise from unconverted pump power that manifests itself as heat and phonon energy. This heat, when coupled with a high thermo-optic coefficient (dn/dT) can give rise to thermal lensing as well as reduced quantum efficiency. These types of issues can be overcome by another novel diode-pumped solid-state laser, the diode-pumped thin disk laser. The thermal limitations in this laser type are mitigated by using a laser medium geometry in which the thickness is much smaller than the diameter of the pump beam. This allows for a more even thermal gradient in the material. Thin disk lasers have been shown to produce up to kilowatt levels of power

Dye lasers



Dye lasers use an organic dye as the gain medium. The wide gain spectrum of available dyes allows these lasers to be highly tunable, or to produce very short-duration pulses (on the order of a few femtoseconds)


Free electron lasers


Free electron lasers, or FELs, generate coherent, high power radiation, that is widely tunable, currently ranging in wavelength from microwaves, through terahertz radiation and infrared, to the visible spectrum, to soft X-rays. They have the widest frequency range of any laser type. While FEL beams share the same optical traits as other lasers, such as coherent radiation, FEL operation is quite different. Unlike gas, liquid, or solid-state lasers, which rely on bound atomic or molecular states, FELs use a relativistic electron beam as the lasing medium, hence the term free electron.




Uses
 
The first application of lasers visible in the daily lives of the general population was the supermarket barcode scanner, introduced in 1974. The laserdisc player, introduced in 1978, was the first successful consumer product to include a laser, but the compact disc player was the first laser-equipped device to become truly common in consumers' homes, beginning in 1982, followed shortly by laser printers.


Some of the other applications include:


Medicine: Bloodless surgery, laser healing, surgical treatment, kidney stone treatment, eye treatment, dentistry


Industry: Cutting, welding, material heat treatment, marking parts


Defense: Marking targets, guiding munitions, missile defence, electro-optical countermeasures (EOCM), alternative to radar, blinding enemy troops.


Research: Spectroscopy, laser ablation, laser annealing, laser scattering, laser interferometry, LIDAR, laser capture microdissection


Product development/commercial: laser printers, CDs, barcode scanners, thermometers, laser pointers, holograms, bubblegrams.


Laser lighting displays: Laser light shows


Cosmetic skin treatments: acne treatment, cellulite and striae reduction, and hair removal.