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An Add-On Optical Interferometer Chamber to Phase Microscopes for Sub-Nanometer 3D and Dynamic Information

Technology
An add-on optical module for microscopes allowing for single frame and dynamic capture of amplitude and phase profiles of transparent or semi-transparent biological and non-biological samples. This easyto-use interferometric device is simply positioned in the camera port of a conventional inverted microscope, enabling quantitative structural, thickness and refractive index measurements in a noncontact, label-free manner.

http://www.ramot.org/sites/default/files/project_images/5-2012-370.bmp

The Need and Potential Application
This interferometric module can measure the dynamic optical thickness with sensitivity of less than 0.5 nanometers, and it does not necessitate using a floating optical table, as opposed to other muchmore-expensive interferometric setups. Such sensitivity enables measurements of very small changes in physical thickness, refractive index, and mechanical properties of biological and non-biological samples. Thus, the technology of interferometry becomes portable and available for wide-spread use.
This powerful imaging technique has significant value for immediate, fluorescent-free biological and medical applications, including red blood cell disease diagnosis (such as malaria, sickle cell anemia and thalassemia), cancer diagnosis and monitoring, and neuronal imaging. In addition, this module can be used for nondestructive testing of transparent micro and nano structures; for example, testing the manufacturing quality of micro-lens arrays.

Advantages

  • Suitable for highly dynamic samples - the device will provide a means of acquiring information on thickness and mechanical properties of live biological cells in a label-free manner with subnanometric precision, and without any sample preparation.
  • Module architecture provides precisions currently available only in research labs with optical tables for averting mechanical vibrations. The proposed module does not require optical lab conditions.
  • Inexpensive, utilizing standard-simple-available optical elements. No gratings are required.
  • Very easy to align and use, even by users without an optical knowledge (attractive for biologists and clinicians).

Stage of Development
We have several working prototypes with successful experiments on biological samples and transparent nano-elements (two journal papers so far).

Patents
Published PCT application No. WO 2013/140396

Supporting Publications
P. Girshovitz and N. T. Shaked, “Generalized cell morphological parameters based on interferometric phase microscopy and their application to cell life cycle characterization,”
Biomedical Optics Express, Vol. 3, No. 8, pp. 1757-1773, 2012
N. T. Shaked, “Quantitative phase microscopy of biological samples using a portable interferometer,” Optics Letters Vol. 37, No. 11, 2016-2019, 2012.