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08 Feb 2008
Using a laser to manipulate cells on a silicon substrate could be the stepping stone towards medical applications such as drug screening. Marie Freebody finds out how Matthew Lang and David Appleyard overcame the challenges of trapping on and through silicon wafers.
When you think about silicon photonics, the first thing that tends to come to mind is silicon lasers, but Massachusetts Institute of Technology's Department of Biological Engineering, US, is focused on something entirely different. Researchers there have just unveiled a way to trap particles, including cells, on silicon wafers with performances that rival trapping on conventional glass coverslips (Lab on a Chip 7 1837).
"My interest is probing how different biological entities adhere to silicon," researcher David Appleyard told OLE. "We are also interested in assembling cells at different relative positions and placing them near sensors for example. Our lab specializes in single-molecule interaction, biological motors and other molecular machinery, and our work is geared towards studying these for the first time in this new environment."
Trapping on silicon has not been without its difficulties, and Appleyard and colleague Matthew Lang have had to experiment with various silicon wafers and optical configurations. After much iteration, it turns out that the optimal set-up is a straightforward extension of conventional trapping involving two optical microscopes and lasers emitting at commonly used wavelengths (see figure 1).
"We went through multiple designs starting from the very complex, but it came down to the fact that it is not a big modification from a conventional optical trap," said Appleyard. "By demonstrating you can do this with laser wavelengths currently in use, part of our hope is that it will be much easier to integrate. I think it is a feasible extension for groups that are not familiar with optical trapping."
Two key challenges
The two key challenges for Appleyard and Lang were getting to grips with silicon and designing a suitable optical set-up. "The main challenge is that you cannot see through silicon and it wasn't an obvious substrate to utilize," commented Lang. "Most optical traps are made through conventional microscopes that allow you to visualize objects with visible wavelengths. Our work required a complete redesign of the imaging system."
To tackle the non-transparency of silicon, it was evident to Appleyard and Lang that a second optical microscope was going to be required. "One microscope is needed to form the optical trap itself, but we could not see what we were doing," said Lang. "We needed to build another microscope to peer into the region directly above the silicon wafer that is non-transparent to visible light. The second microscope allowed us to visualize this and also to capture some of the signals that we use to calibrate our optical trap."
Picking the appropriate silicon wafer for the experiment was also an issue. Lang and Appleyard started with a single-side polished wafer before moving on to a double-sided polished wafer due to its favourable optical properties.
"As glass coverslips are typically 150 µm thick, we thought that we might need equivalent silicon wafers," said Lang. "But because silicon has different optical properties and a different index of refraction, we were able to use 200 and 500 µm thick wafers. It should be feasible to use wafers up to 800 µm thick."
Trapping geometries
Running in tandem with a conventional microscope, the team's second microscope uses a 1064 nm laser to trap the particles and a 975 nm laser (following the same beam path) to track the position of the trapped particles.
"Silicon starts to become transparent around 1000 nm and continues to become transparent the further you get into the infrared," said Appleyard. "The main reason we went with 1064 nm is that it is a very common laser for biological applications. Water also has a low absorption at 1064 nm, so this means that we will not heat up and damage the biological organisms at this wavelength."
Appleyard and Lang's instrument offers two distinct geometries for trapping, which are referred to as "before" and "through". In the before system the trap focus is formed before the beam path reaches the silicon substrate, whereas in the through system the laser penetrates the silicon substrate and then forms the trap focus. The two geometries require a reflective imaging arrangement and the dual microscope set-up.
"Before is probably the more flexible option, with the trap being formed before it penetrates the silicon wafer," explained Appleyard. "This is a convenient option if you want to move cells on top of a sensor."
The through set-up is slightly more complicated. "One microscope objective focuses the laser to a point on the other side of the silicon so the focal point occurs after the laser beam has penetrated the silicon," said Appleyard. "The second microscope objective, on the same side as the focal point, focuses visible light to the same point to give you an idea of what you are manipulating. This would be useful for microfluidic devices."
The researchers estimate that approximately 10 mW is the minimum optical power required to trap a particle, although the precise figure will depend on the size of the particle, what the particle is made of and how tightly focused the beam is. They add that around 2 mW at 975 nm is sufficient to perform the position tracking.
To date, Appleyard and Lang have successfully trapped and manipulated glass and polystyrene spheres up to 5 µm in diameter, as well as E-coli, and are confident that their system could cope with rods and elliptical bacteria. They have also used a time-sharing technique, which they liken to someone spinning plates, to trap multiple particles simultaneously.
"We trap one particle and then juggle the trap to another particle," explained Lang. "We can juggle 3, 4 or up to 16 particles in this way. The trick is to return to the first particle before it moves through Brownian motion. We're running at about 1 kHz so if we have five particles, we're coming back to each one 200 times per second."
To move the particles in two dimensions, the researchers simply translate the silicon wafer using a positioning stage or manipulate the position of the laser using optical elements. There is also an element of 3D control, which is achieved by adjusting the position of the beam focus with respect to the silicon surface.
Applications The motivation behind this work has been to explore what Appleyard and Lang call the biological–electrical interface. "We want to connect some of the sensors that are available on microchips with biological systems that are used for disease diagnosis," said Appleyard. "For example, using the precise positioning of the trap to connect cells to sensors and do things such as active assembly of cells at specific locations on a chip."
And Lang agrees. "The silicon community can make exquisite structures and sensors, and control properties to nanometre levels," he said. "It is going to be critical to explore the interface between these structures and biology as well as peptide interactions at these interfaces."
Non-biological applications could also benefit from this trapping technique. "Instead of building things in two dimensions on silicon wafers, techniques like this or a combination of this and self-assembly, can produce three-dimensional structures," concluded Lang. "Optical traps could be added to MEMS where we could fabricate components separately, flow them into position and build up a structure using an optical trap instead of one complex fabrication step."
• David Appleyard and Matthew Lang work in MIT's Department of Biological Engineering. For more information visit the Lang Laboratory website, http://web.mit.edu/~langlab/.
• This article originally appeared in the January 2008 issue of Optics & Laser Europe magazine.
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