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Pocket Laboratory

Increased random laser efficiency opens the door for the manufacture of low-cost microchips for medical exams

Léo Ramos Chaves Laser-sculpted microchannels at Ipen: network designed to allow the mixture of fluids and reagentsLéo Ramos Chaves

Breaking energy efficiency records when generating laser beams is becoming routine for Niklaus Wetter, a Swiss physicist who has been working in Brazil since 1988. For the last three years, he has been the director of the Lasers and Applications Center of the Nuclear and Energy Research Institute (IPEN) in São Paulo. In 2015, Wetter and physicist Alessandro Melo de Ana, of Nove de Julho University, presented a new configuration of lenses and mirrors for laser generators in the journal Optics Express. It uses crystals containing the chemical element neodymium. With the new arrangement, the device, one of the most used devices in the world in industrial, medical and research settings, was able to use 60% of the energy transferred to its crystal to generate laser light, surpassing the previous record of 50% for this type of equipment.

Now, with Brazilian physicist Julia Giehl and German physicist Felix Butzbach, both former IPEN students, and Spanish physicist Ernesto Jimenez-Villar, from the Federal University of Pernambuco (UFPE), Wetter has achieved an even greater advance in energy efficiency for a different type of laser—the random laser. This variety of laser has drawn the attention of physicists and engineers in recent years due to its low cost and because it uses very small equipment (see Pesquisa FAPESP Issue nº 247). Instead of a using a crystal, random laser equipment produces light with characteristics like those of a conventional laser using a liquid containing micro- or nanometric particles in suspension or a mixture of particles in the solid state (in the form of a powder). The problem is that the efficiency of this type of laser tends to be low. The solutions and mixtures of microscopic particles convert a maximum of 2% of the energy received into laser light. Calculating details of how the laser is generated and amplified as the light is reflected several times by the particles, Wetter’s team discovered how to increase the efficiency of this conversion, which has now reached 60%. “This result is comparable to that of the best [conventional] solid-state lasers available on the market,” states Wetter.

The secret, the researchers discovered, was to mix particles of different sizes. In the experiments, they used 54-micrometer-diameter grains of a crystal and grains almost 10 times smaller, just six micrometers in diameter. In the mixture, the smaller particles filled in the space between the larger ones, creating pockets that increased local scattering of light by 30%. Each time light is scattered, more energy is incorporated into the laser. The final result is a 160% increase in the power of the emitted laser beam. These results were presented on January 31, 2017 at Photonics West 2017, in San Francisco, an important international conference on laser technology. “We hold the current record,” commemorates Wetter.

At IPEN, the Swiss physicist has always worked on improving high-power, precision laser sources, produced using high-purity crystal equipment and lenses and mirrors with special surfaces. These devices cost tens of thousands of dollars. Since 2008, however, his laboratory has been working in parallel on another line of research, that of improving random lasers, whose production costs, according to Wetter, could one day drop to pennies.

His motivation is the technological impact that random lasers promise to have on the development of compact, portable and disposable biomedical laboratories, known as “labs-on-a-chip.” These cards, made of glass or plastic, contain microscopic channels and reservoirs with a thickness on the scale of millimeters or micrometers that allow the storage, passage and mixture of tiny amounts of liquids. The researchers design these networks of channels and reservoirs in a way that permits the mixing of samples of blood, saliva and other body fluids with chemical reagents needed to carry out laboratory exams.

Léo Ramos Chaves Researchers illuminate a solution of microparticles with a green laser, generating a random red laserLéo Ramos Chaves

Handheld laboratories
The goal is to one day use this technology to offer some exams to people without easy access to clinics and laboratories, such as homebound infirm elderly or poor communities located far from urban centers. There are already some lab-on-a-chip models ready for use. In Brazil, a multi-disciplinary team coordinated by physician-scientist Marco Aurélio Krieger of the Oswaldo Cruz Foundation (Fiocruz) in Paraná State, is developing a plastic chip in the form of a three-centimeter-diameter disk capable of detecting up to 20 infectious diseases by analyzing a drop of blood (see Pesquisa FAPESP Issue nº 192). The existing devices, however, only perform simpler diagnoses. They identify, for example, the presence of a pathogen in a drop of blood, but cannot quantify compounds in biological samples.

Some obstacles block the development of more sophisticated, cheaper versions of the labs-on-a-chip. Physicists and engineers already understand the manufacturing techniques used to create the microchannels in which the chemical reactions employed for the most common medical exams—such as blood sugar, cholesterol or to detect infections—take place. But control of these reactions and analysis of the results still require that the chip be attached to external equipment. This equipment could be something simple, such as an ultraviolet light bulb used to evaluate the exams done utilizing the chip developed by Krieger’s team, or a high-precision laser source needed for more sophisticated tests such as those that determine levels of cholesterol, insulin or other molecules in the blood.

In order to develop labs on a chip independent of external equipment, the plastic or glass card must include a structure capable of producing a leaser beam with well-defined direction and wavelength (color), in addition to sufficient power to pass through a microchannel containing blood, saliva or another biological fluid. After passing through the sample, the light must still reach a sensor that will analyze changes in the intensity and color of the laser—alterations of these properties could indicate the presence of molecules and their quantity in the biological material.

In the United States and Europe, some universities and technology start-ups are already manufacturing diagnostic chips able to carry out this type of analysis of biological material. But these devices still use lasers produced by semiconductor diodes or conventional laser-generating crystals that, despite being relatively small, cost hundreds of dollars. The devices that generate high-quality conventional lasers are expensive because they require the use of special polished mirrors and crystals made of very pure material. The purer the crystal and the more polished the mirrors, the more efficient the laser produced and the better defined its properties, which must be precise for biochemical analyses.

The physicists hope to solve this cost problem by using a random laser instead of a conventional one. “I see random lasers as the cheapest way to insert a laser source inside a lab-on-a-chip,” says Wetter.

In an article published in July 2016 in the journal Applied Optics, Wetter’s team, together with the groups led by engineers Marco Alayo and Marcelo Carreño, of the University of São Paulo Polytechnic School (Poli-USP), describe the manufacture and operation of a random laser source that can be easily integrated into a lab-on-a-chip. In the experiment, an external light source stimulated the molecules of a solution containing rhodamine, an organic dye that emits light when illuminated. Instead of mirrors, microscopic particles of titanium dioxide (TiO2) amplify the light produced by rhodamine. TiO2, also known as rutile, is the main component of white paints and sunscreens, has a strong capacity to reflect and spread light. When they correctly adjust the concentration of rutile particles to the size and format of the microchannel containing rhodamine, the researchers can generate a random laser beam with well-defined direction and color.

Technical obstacles
Wetter and his collaborators work with different materials to produce random lasers and try to guide the path of this light inside the microchannels. The goal is to overcome the technological obstacles that prevent manufacture of a cheap and disposable lab-on-a-chip that works with the aid of a cell phone. “We want to use the flash from a cell phone camera as a light source to generate the random laser on the chip,” explains the physicist. The camera of the device would serve to analyze the change in the properties of the laser beam that passed through the sample. “If properly done, this device could perhaps be used in communities far from urban centers to provide diagnoses available only in specialized laboratories today,” says Wetter.

There is still a lot of work to do. At the moment, the random lasers and the active medium developed at IPEN demonstrate that a device of this type can be developed. But there are important barriers to overcome in order to obtain a device that can be used by health professionals. One of them is to decrease the energy needed to activate the emission of light by rhodamine, currently thousands of times higher than that provided by the flash from a cell phone.

An optical phenomenon recently observed by Wetter and Jimenez-Villar may help reduce the energy required to produce the random laser. By coating the rutile particles with a thin layer of silica (SiO2), the researchers produced an effect called Anderson localization for the first time in this type of laser. This increases the interaction between the light and the material, thus reducing the energy needed to generate the laser by more than a factor of 10. Despite this, the flash of a cell phone would still not be sufficient to generate a laser with enough power to analyze a biological sample. “We need to improve the efficiency of the entire device so it can work with a weaker beam of light,” says Wetter.

“The technology of random lasers is evolving rapidly,” says physicist Vanderlei Bagnato of USP, São Carlos. He notes, however, that other types of lasers are being developed for inclusion in labs-on-a-chip, such as vertical cavity lasers. “None are ready yet.”

1. Micromachining with ultrashort laser pulses applied to the production and control of optofluidic circuits (nº 2013/26113-6); Grant Mechanism Thematic Project; Principal Investigator Wagner de Rossi (IPEN); Investment R$3,614,777.92.
2. Lasers in highly diffuse media for structural analysis of tissues (nº 2012/18162-4); Grant Mechanism Regular research project; Principal Investigator Niklaus Ursus Wetter (IPEN); Investment R$279,768.38.

Scientific Articles
JORGE, K. C. et al. Directional random laser source consisting of a HC-ARROW reservoir connected to channels for spectroscopic analysis in microfluidic devices. Applied Optics. V. 55 (20). p. 5393-98, 2016.
WETTER, N. U. and DEANA, A. M. Influence of pump bandwidth on the efficiency of side-pumped, double-beam mode-controlled lasers: Establishing a new record for Nd:YLiF 4 lasers using VBG. Optic Express. V. 23. p. 9379-87, 2015.
REIJN, S-M. et al. Enabling focusing around the corner in multiple scattering media. Applied Optics. V. 54. p. 7740-46, 2015.
JIMENEZ-VILLAR, E. et al. Anderson localization of light in a colloidal suspension (TiO2@Silica). Nanoscale. V. 8. p. 10938-46, 2016.