A chip-scale microscope for high-throughput fluorescence imaging

Chip technology presents a whole different view on microscopy. Chips are compact and can integrate multiple functionalities. The scaling possibilities could allow chip-based microscopes to be produced at a fraction of the cost of standard devices. Niels Verellen, principal scientist at imec, has designed a high-resolution, on-chip microscope with a scalable field of view. At the halfway point of the five-year project, he talks about the early successes and challenges ahead.

Lens-free fluorescence microscopy

To downsize the microscope, Niels Verellen's team removed the quintessential part of standard optical microscopes: the lens. Lens-free options exist for , which directly image scattered light. Imec's lens-free microscope, for example, uses the interference pattern of the excitation light to reconstruct the image holographically. These solutions don't work for fluorescence microscopy because fluorescence light is not coherent, meaning that there is no time-distance relationship between the excitation light and the fluorescence emission.

Niels Verellen says, "The goal of the ERC project is to achieve the same advantages as the existing lens-free optical microscope (small size, scalability, large field of view and high resolution) for . The operating principle of our microscope is similar to that of a traditional confocal laser scanning fluorescence microscope. The lens-free microscope contains an image sensor (a pixel array), topped with an integrated consisting of waveguides and phase modulators that form focused illumination spots. Unlike in a that operates traditionally with one focus point, we can generate and scan many spots simultaneously."

The fluorescence microscope on-chip is compact with a large field of view and high resolution. Credit: imec

The concept of the fluorescence microscope on chip. Illumination spots are generated in the photonic circuit. The imager picks up a signal where the light excites the fluorophore. Credit: imec

The interference patterns can be precisely controlled to form illumination spots. Credit: imec

Top: 200mm Si wafer with integrated photonic circuits. Bottom: A scanning electron microscope (SEM) image showing the cross-section of a photonic circuit integrated on an imager. Credit: imec