3. EMCCD vs ICCD – experimental comparison

The EMCCD

Andor Technology iXon DV887 back-illuminated (up to > 90% QE). 512x512 frame-transfer sensor, 16 µm2 pixel size, capable of delivering up to 34 full frames/sec.

The ICCD

Stanford Photonics XR Mega 10 ICCD, containing a GenIII+ intensifier and 1280 x 1024 CCD sensor, 6.7 µm2 sensor pixel size, capable of 15 frames/sec at full frame readout. The sensor is fiber-coupled to the intensifier tube, with a ~ 1.5 to 1 tapered fiber, yielding an effective pixel size of >10 µm2. Binning (2x2) of the ICCD was used to enable shorter exposure times (faster frame rates) to be employed in this camera, whilst also making the effective pixel size more comparable to that of the EMCCD (better for more accurate sensitivity comparisons). Such binning should result in more favourable S/N performance (a 2x2 binned superpixel collects 4x more light that a non-binned pixel).

The comparison

In order to perform a direct performance comparison between the BV-EMCCD camera and the Gen III+ ICCD, a series of Fluo-4 loaded rabbit urethra smooth muscle cells were imaged using a Nipkow confocal spinning disk, taking a short kinetic series (10 frames) with one camera, then performing the same analysis with the other camera directly after with the same cell still in place. The order of which the images were recorded was alternated for each subsequent cell, in order to rule out photobleaching effects on the differing S/N levels. In general, largely due to the rapid confocal nature of the technique and the short 33 ms exposure times employed (2x2 binning of the ICCD was necessary in order to achieve this exposure), the fluorescent images represent extremely low photon fluxes. All cells imaged were within the same field of cells and subjected to identical dye loading times. However, it was obvious that some cells were inherently weaker than others. This is due to slightly different loading efficiencies, focal fine position and also, the laser power was purposefully varied slightly in order to produce different degrees of signal intensities. The important point was that each cell was imaged ‘like-for-like’, varying only the camera.

raw and smoothed lowlight fluorescent images

(A) Comparative raw and smoothed low-light fluorescent images recorded of a live smooth muscle cell using the BV-EMCCD and the Gen III+ ICCD
(B) Further comparative cell images of weakly loaded cell, representative of an image close to the ‘photon shot noise’ detection limit; 33 ms exposure time per frame; high EMCCD or ICCD gain setting throughout to eliminate read noise.

Figure 1(A) shows one of the cells recorded with each camera type, both before and after applying a smoothing algorithm. It is clear that both signal contrast and resolution is markedly better in the case of the images recorded with the BV-EMCCD. The effect of smoothing is to enhance the contrast further between fluorescent signal and background, at the expense of some resolution. However, even after smoothing of each image, the same improvements are noticeable in the BV-EMCCD images compared to the corresponding ICCD image. Figure 1(B) shows a further representative cell comparison from this experiment, this one of a weakly loaded cell representing a signal intensity that is close to the ‘photon shot noise’ detection limit for this exposure time. It is clear that signal intensity and image contrast is markedly better for the image recorded with the EMCCD, a direct function of a higher S/N ratio afforded by the higher QE of the EMCCD detector (both types of detector have overcome the read noise detection limit). The photon flux was so low that this cell could barely be detected at all with the ICCD, but is certainly identifiable with the EMCCD. The superior signal of the EMCCD is to be expected given the markedly restricted QE of ICCDs compared to the unrestrained QE of the BV-EMCCD. Indeed, at the 516nm max. of Fluo-4 dye, the BV-CCD should have > x2 QE than a GenIII+ photocathode. This should result in > x1.4 increase in Signal-to-Shot Noise ratio.

Furthermore, the resolution from the BV-EMCCD is markedly better, and one can for example more easily identify areas of intracellular dye compartmentalization. This resolution improvement arises to a large extent from the different electron amplification technology used in the EMCCD, which virtually eliminates the pixel cross-talk that is inherent in ICCD measurements (yielding a form of instrumental blurring), but also from the slightly larger area of the 2x2 binned pixel required to run at a faster readout speed (and shorter exposure time). In comparison, the EMCCD produces images of stark resolution – post-acquisition smoothing can be applied artificially through software if required but this is the researcher’s choice. It is interesting also to note that, in terms of sensitivity, a greater number of photons should hit the slightly larger pixel area of the 2x2 binned ICCD than that of the non-binned BV-EMCCD, yet the latter camera clearly maintained a clear S/N advantage (without the need to sacrifice resolution for speed).

It is important to note that all of the images shown here are of extremely weak fluorescence confocal signals, and would be lost entirely within the read noise floor if it were not for the respective signal amplification technologies.

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4 Other detector technologies?