Extreme High full well capacity camera to increase the sensitivity in interferometric microscopy – interview with MIT

Posted by Gretchen Alper on Thu, Jul 21, 2016

Adimec interviews Poorya Hosseini of MIT to discuss the use of extreme high full well capacity camera in interferometric microscopy

Optics Letters recently published a paper titled “Pushing phase and amplitude sensitivity limits in interferometric microscopy”.  For this research, the Adimec high full well (HFW) Q-2HFW-CXP camera was used.  The new 2 Megapixel CoaXPress camera (Q-2HFW-CXP) brings a 1440x1440 resolution at up to 550 fps based on 12 micron pixels. The design of the pixels in this global shutter CMOS image sensor, CMOSIS CSI2100, is optimized for maximum full well performance. The full well capacity (FWC) of over 2 million electrons per pixel is quite unique that is around 100 times higher compared to commonly available high speed CMOS sensor technology today (reference: 20 kel full well). This million-level electrons full well capacity per pixel results in extremely good shot noise performance of up to 63 dB SNR, making it possible to accurately detect very weak contrast variations in bright environments. The camera was developed as part of the FP7 funded CAReIOCA consortium.


I spoke with Poorya who is the lead author of the paper about his research and the types of innovations this technology can enable.


Q. What kind of research are you conducting with Adimec’s high full well capacity camera?

Well, I guess that in simple terms we develop microscopes and imaging technologies for biological or medical applications. My own work has been mainly focused on developing technologies for studying biomechanical factors in blood disorders such as sickle cell disease. The ability to monitor biophysical properties at individual cell level allows us to study the changes in these properties in various pathophysiological conditions and in response to various treatments. The Adimec camera will allows us to make these measurements with unprecedented precision. The same technologies can be used in a variety of other biological and non-biological applications where a small signal needs to be extracted from a large background.


Q. Why is this camera of interest to you?

There has been some debate on what typically limits the sensitivity of the phase measurements in interferometric microscopy and holographic microscopy that has been a few nm in terms of optical path length. We hypothesized that photon shot noise sets the current limit rather than other noise sources such as mechanical vibrations or power fluctuations of the illumination source. After some theoretical calculations and showing shot noise is indeed the limiting factor, we needed a tool to see how far we can push shot noise down before we hit the mechanical limits. This is only possible when you can collect a huge number of photons in a short period of time using this camera, and of course lots of light


Q. What type of improvement did you see with the HFWC camera?

 Using Adimec camera, we experimentally showed that the limit on the sensitivity of the optical path length could be as low as a few picometers which is additionally a testament to the stability of our near-common-path interferometers. Of course if you want to go even beyond this limit, you would want to collect more photons even more quickly to reduce the influence of mechanical vibrations that tends to be more significant at low frequencies. Basically before your system has a chance to see those vibrations, you are done with your measurements!


Q. Do you use the HFW camera for other applications as well?

 Yes, we are now developing another high sensitivity phase microscope system that uses the HFW camera to study neuronal signal transduction along axon on a label-free manner. Basically, each time a neuron “fires” there are some very subtle changes in the local optical properties of the cell. The firing action happens quite fast - within a few milliseconds. Therefore, to detect these firing actions you need to have a system which is both fast with ultra-high sensitivity in detecting the small changes in optical properties. We think HFW would be of great advantage in that project. That aside, the field of interferometric microscopy and holographic microscopy is growing fast and several companies has been formed around it just over the past few years where a camera with higher full well capacity could be quite useful. Besides phase microscopy, another of my colleagues is developing a wide-field measurement technique for nonlinear Raman signals that is often as low as one part in a million of the background signal using the HFW camera. If successful, this new Raman microscope may allow the study of transdermal drug delivery or the diagnosis of diseases such as melanoma.    


Q. What's the next step in your research? Which improvements are required in camera specifications to even get further progress in your research?

Well, as an initial step, we have shown that one can push the sensitivity of phase and amplitude in interferometric microscopy to new limits. I am planning to use this capability to study subtle changes that biological systems, such as my favorites that is the red blood cells, experience during the pathology of various disease and in response to the different treatments. In terms of improvements in the camera, that is an easy question to answer -  we always want cameras with even deeper well depths, more pixels, and faster readout rates. We need cameras with the capacity to collect more photons per unit time, sky is the limit!



Topics: Applications

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