Scoping out the best microscope for the job
Microscopes are fantastic tools for seeing things which are too small for the human eye to detect. But one microscope does not solve all problems. The Applied Optics Lab at the Australian National University, led by Dr Steve Lee, is working on customising optical microscopes to meet the particular needs of life science researchers.
By Elizabeth Thomsen
Microscopes are fantastic tools for seeing things which are too small for the human eye to detect. But one microscope does not solve all problems. The Applied Optics Lab at the Australian National University, led by Dr Steve Lee, is working on customising optical microscopes to meet the particular needs of life science researchers.
Near real time imaging of living cells
The team have built a microscope based on similar technologies to retail bar-code scanners and office laser printers. In bar-code scanners, a laser bounces off a spinning polygon mirror, quickly scanning across a sample. In this microscope a more powerful laser is used, and the spinning mirror has more sides. The result is a microscope that can scan across a biological sample in a few thousandths of a second.
The microscope can analyse complex medical problems and be applied to samples ranging from blood disorders to neurological disorders. It can be used in living, anaesthetised animals, and can film moving blood cells and neurons as they fire, with almost real-time imaging at up to 800 frames per second.
The microscope has double the speed of microscopes on the market with the same imaging resolution. One of the advantages of the high-frequency image capture is that the impact of movement and breathing can be eliminated. This has been particularly useful in early testing of the microscope on living mice. These movements can cause distortion in other imaging techniques. The same microscope can be used with a range of scanning speeds, allowing the user to get the information they need, whether that be a high intensity signal at a slow frame rate, or to capture high speed events using a fast frame rate.
Holographic microscopy for blood-borne diseases
The team has also turned its attention to blood-borne diseases such as sickle cell anaemia, malaria, and beta thalassemia. The size and shape of blood cells often reveal early signs of disease. The team have employed holograms to capture the three dimensional structure of the cells. Holograms may remind some people of seemingly three dimensional postcards based on a similar technique. But holography is a clever way of recreating the light that came from an object, and can be used to create a powerful microscopy tool.
The team have developed an automated holographic microscope for high throughput disease diagnosis. By combining a number of computer vision techniques including shape recognition and machine learning, the microscope can operate without manual intervention to measure red blood cells and determine whether they are infected or not. The technique has passed initial tests on both transparent and turbid systems, and on thick samples (which can be difficult to image). The next step is to test the microscope on live cell cultures.
Wearable microscopy
Researchers and healthcare professionals typically use scientific instruments which are complex, expensive, and unwieldy. For many applications such as point-of-care medicine, geophysics research, education, and nature conservation, it is desirable to use cheap, easily made add-ons to portable devices such as laptops and smartphones. The Applied Optics team have a new solution to this problem with a wearable microscope.
The microscope has several elements: a camera, a display, and a computer. The camera is mounted on a thimble on the index finger, the display is worn on a wristband, and the computer is a credit-card sized Raspberry Pi. The result is a microscope that has higher resolution and is significantly smaller than a similar hand-held device such as a webcam. It also leaves the user essentially hands free to work with the subject – a particularly useful feature when the sample is obstructed such as for imaging insects hidden under leaves.
The most exciting feature of this microscope is that almost the entire system can be fabricated from a regular desktop 3D printer, and commercially available, inexpensive materials. The lens is created using 3D printed tools and commercially available materials (such as transparent silicone, polydimethylsiloxane, and acrylonitrile-butadiene-styrene). This approach allows the user to make the lenses themselves, and potentially customise them to their own needs. The brace to attach the thimble camera to the user’s finger is also 3D printed. The team are now working on further improving the quality of the image from the camera using clever computing techniques such as Fourier Ptychography.
Custom microscopes
The Applied Optics team is interested in customising microscopes to the needs of researchers that study the vascular and immune systems to combat infectious diseases and cancer progression. Dr Steve Lee says, “We focus on the problem not the technique, so that we can produce something that is useful.”
Photo credit: Steve Lee