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The drawback is that the resolution is lower because the specimen is now being sampled (in the example above) by four large pixels instead of 16 small ones. The images below broadly illustrate the effect of increasing binning factors on resolution. In the high resolution imaging modes used in fluorescence microscopy you would have to use binning factors higher than 2 to experience the pixelation seen in the images on the right. 
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Numerical Aperture (NA)
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