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12 Apr 2007
Precision laser micromachining is at the heart of a project to fabricate lasers and LEDs with reaction chambers formed directly into the semiconductor device. Nadya Anscombe questions Huw Summers about the work of the UK’s Optical Biochip Consortium.
Water and electricity don’t mix. Although the idea of placing a biological sample inside a reaction chamber formed on a semiconductor wafer goes against conventional wisdom, it is one that the UK’s Optical Biochip Consortium is successfully pioneering.
Lab-on-a-chip technology has applications in genomics, chemical analysis, environmental monitoring, medical diagnostics and cellomics. Advances in microengineering have enabled the development of highly portable and even disposable devices for applications such as fluorescence sensing where the optical elements, excitation sources and detectors are incorporated directly into a chip.
But most lab-on-a-chip designs are simply scaled-down versions of macro systems, with the optical excitation source, detector and biological sample remaining as distinct and separate entities. Microscaling and integration brings these elements closer together, but their operation within a fluorescence assay platform remains essentially the same as the macro system.
Huw Summers and his colleagues from Cardiff University, the University of Wales Bangor and the Gray Cancer Institute hope to change this. They are working on light-emitting devices (lasers or LEDs) with reaction chambers formed directly into the semiconductor device. These chambers, or microwells, enable close-range illumination to maximize excitation efficiency without the use of optical elements, and also give precise control over the assay location.
The group has already built and tested demonstrators to show individual aspects of the optical biochip in action. These demonstrators, around the size of a mobile phone, can perform live cell biology using fluorescence techniques for analysis. They are unique because they incorporate fine temperature control, delivery of cell nutrients and control of gaseous environment such as CO2 levels.
“We envisage them being used for various point-of-care applications,” Summers told OLE. “This includes cancer diagnosis and could eliminate the need for patients to wait weeks for test results to come back from a central laboratory.”
Making the wells
The Optical Biochip Consortium is working on a variety of demonstrators, but the two main types involve LEDs or lasers. In the LED-based systems, the biological sample sits in a well within the LED and is illuminated; whereas in the laser-based systems the biological sample becomes part of the active medium of the laser.
In both cases, the reaction chambers are formed in standard semiconductor wafers using a combination of femtosecond and excimer-laser micromachining. The challenge has been to fabricate chambers of varying size and shape in the surface of a semiconductor wafer with minimal post-processing while maintaining the light-emission capability of the material itself.
The wafer also needs to be protected from the aqueous solutions found in cell samples. This is done by lining the microwells with an optically clear epoxy layer to mechanically and electrically isolate the semiconductor wafer from any analyte.
“The fabrication technology is independent of the semiconductor wafer design, so a microwell can just as easily be fabricated within a laser structure as within an LED,” commented Summers.
The researchers used a direct-write machining system that incorporates a Ti:sapphire laser with a pulse duration of 120& thinsp;fs and a beam-power density of up to 3.5 W/cm2. The beam was typically focused to a 20 µm spot delivering power densities of up to 0.3 MW/cm2.
Using femtosecond laser micromachining it is possible to machine semiconductor wafers in a manner that allows arbitrary-shaped 2D light sources to be created. The delivery of high-energy laser pulses in time periods close to 100 fs leads to an ionizing ablation process capable of cleanly removing only the region of the workpiece illuminated by the tightly focused laser beam.
In the case of light-emitting semiconductors, where the emission occurs in a defined junction region typically located within 1.5 µm of the surface of the wafer, the ionizing ablation process allows the junction to be cleanly machined without affecting its emission. The lack of large physical debris from the machining process reduces the likelihood of the semiconductor junction being short circuited and the tightly focused beam restricts machining to a highly defined area or path.
Laser micromachining allows real-time monitoring of the semiconductor device while the holes are being ablated. “This is a real advantage of the technique,” explained Summers. The introduction of holes in the laser structures reduces the amplification length and increases the optical loss, which in turn increases the laser threshold. “But this increase of around 10–20% is surprisingly small,” said Summers. “Using micromachining means that we can run the laser while it is being ablated and can therefore machine it to produce a given increase in threshold current.”
New directions, crucial differences
This is the direction in which the group’s work is now going. The LED work has been completed and is ripe for commercialization. The group is now focusing its efforts on developing an optical biochip based on laser technology.
There is a fundamental difference in how these two technologies are used. LEDs, like traditional light sources used in biotechnology, excite specially designed fluorescent markers that can reveal important features about each cell, such as how it responds to a drug or whether or not it is diseased. However, making the cell part of a laser cavity measures the effect of the cell itself on the laser output and not the fluorescence from the marker. “The laser light passes through the cell many times,” said Summers. “This gives an intense laser signal rather than a diffuse and weak fluorescence signal.”
Specimens placed into the laser cavity behave like tiny lenses as light traverses the sample. Because human cells are very transmissive and have low absorption between 600 and 1200 nm, they are sampled hundreds of times as the light bounces between the mirrors. Within the cell laser, the measurement is based on cell scattering and refractive index, not absorption. The idea is that lensing due to the refractive index change at the cell and/or light scattering controls the amount of light that can reflect around the laser cavity.
The devices currently used by the Optical Biochip Consortium have wavelengths of 630–650 nm, but Summers and his colleagues are planning to use infrared wavelengths as well (800–1100 nm), as this minimizes absorption of light by the cells.
The group is currently looking for more funding to do further research in this area. Meanwhile, patents have been filed and commercialization routes are being investigated for particular demonstrators that have immediate application.
• This article originally appeared in the April 2007 issue of Optics & Laser Europe magazine.
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