Photo Credit: © ChipScope
For
half a millennium, people have tried to enhance human vision by technical
means. While the human eye is capable of recognizing features over a wide range
of size, it reaches its limits when peering at objects over giant distances or
in the micro- and nanoworld. Researchers of the EU funded project ChipScope are
now developing a completely new strategy towards optical microscopy.
The
conventional light microscope, still standard equipment in laboratories,
underlies the fundamental laws of optics. Thus, resolution is limited by
diffraction to the so-called ‘Abbe limit’ – structural features smaller than a
minimum of 200 nm cannot be resolved by this kind of microscope.
So
far, all technologies for going beyond the Abbe limit rely on complex setups,
with bulky components and advanced laboratory infrastructure. Even a
conventional light microscope, in most configurations, is not suitable as a
mobile gadget to do research out in the field or in remote areas. In the
ChipScope project funded by the EU, a completely new strategy towards optical
microscopy is explored. In classical optical microscopy the analyzed sample
area is illuminated simultaneously, collecting the light which is scattered
from each point with an area-selective detector, e.g. the human eye or the
sensor of a camera. In the ChipScope idea instead, a structured light source
with tiny, individually addressable elements is utilized. As depicted in the
figure, the specimen is located on top of this light source, in close vicinity.
Whenever single emitters are activated, the light propagation depends on the
spatial structure of the sample, very similar to what is known as shadow
imaging in the macroscopic world. To obtain an image, the overall amount of
light that is transmitted through the sample region is sensed by a detector,
activating one light element at a time and thereby scanning across the sample
space. If the light elements have sizes in the nanometer regime and the sample
is in close contact to them, the optical near field is of relevance and super
resolution imaging may become possible with a chip-based setup.
To
realize this alternative idea, a bunch of innovative technology is required.
The structured light source is realized by tiny light-emitting diodes (LEDs),
which are developed at the University of Technology in Braunschweig, Germany.
Due to their superior characteristics in comparison to other lighting systems,
e.g. the classical light bulb or Halogen-based emitters, LEDs have conquered
the market for general lighting applications in the past decades. However, to
the present point, no structured LED arrays with individually addressable
pixels down to the sub-µm regime are commercially available. This task belongs
to the responsibility of TU Braunschweig within the frame of the ChipScope
project. First LED arrays with pixel sizes down to 1 µm have already been
demonstrated by the researchers, as depicted in the figure. They are based on
gallium nitride (GaN), a semiconductor material that is commonly used for blue
and white LEDs. Controlled structuring of such LEDs down to the sub-µm regime
is extremely challenging. It is conducted by photo- and electron beam
lithography, where structures in the semiconductor are defined with high
precision by optical shadow masks or focused electron beams.
As
a further component, highly sensitive light detectors are required for the
microscope prototype. Here, Professor A. Dieguez’ group at the University of
Barcelona develops so called single-photon avalanche detectors (SPADs) which
can detect very low light intensities down to single photons. First tests with
those detectors integrated into a prototype of the ChipScope microscope have
already been conducted and have shown promising results. Moreover, a way to
bring specimens into close vicinity of the structured light source is vital for
proper microscope operation. An established technology to realize this utilizes
microfluidic channels, where a fine system of channels is structured into a
polymer matrix. Using high-precision pumps, a micro-volume liquid is driven
through this system and carries the specimen along to the target position. This
part of the microscope assembly is contributed by the Austrian Institute of
Technology AIT. Further partners: Medical Univ. of Vienna, Univ. Tor Vergata
Roma, LMU Munich and FSRM, Switzerland.