Researchers at the Institute of Photonic Sciences (ICFO) have developed a low-cost, compact, portable on-chip light microscope capable of carrying out ultrasensitive analysis of transparent objects.

Holographic, phase contrast and differential interference contrast (DIC) microscopes have been developed in recent years for making transparent objects visible—opening new pathways for the study and characterization of structures such as biological cells or protein layers. While these technologies offer high sensitivity and resolution, they have proven to be severely limited as far as field of view (FOV) and depth of field (DOF)—major drawbacks for large samples, where a scanning method is mandatory and time consuming.

There is always a trade-off: when trying to improve one parameter with a specific combination of lenses, the other will deteriorate. Therefore, in recent years, research has been focused on developing microscopes without optical lenses or objectives that could offer unprecedented FOV while maintaining fair sensitivity and resolution.

ICFO researchers have now built a microscope made with consumer electronic products capable of simultaneously measuring nanometer-thick changes over a large volume (0.5cm^3) in transparent objects such as glass. The researchers developed a large-FOV interferometric on-chip, lens-free microscope based on a novel design with a very high axial sensitivity and DOF, applying a technique suitable for use in microarray platforms for the detection of proteins without the need for labels.

A large-field-of-view interferometric microscope can detect single protein layers. Image credit: ICFO.A large-field-of-view interferometric microscope can detect single protein layers. Image credit: ICFO. By using collimated polarized light, the scientists were able to reconstruct an image by shining light through the transparent sample to observe and analyze the phase shift and interference intensity pattern, a technique known as phase-shifting interferometry.

”The device means a major step forward for light microscopy techniques, especially for microarray platforms, since it could definitely be used as a point-of-care tool in the diagnosis and treatment of major diseases such as sepsis, a critical area where fast and accurate results can translate into life-changing health outcomes for individuals," says Valerio Pruneri, an ICFO researcher who helped develop the microscope.

The new device has proven to be low-cost and compact, making it an ideal device to be fully integrated into cameras of smartphones or tablets and used for detecting and scanning transparent objects or surfaces.

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