New metalens technology from MGH and SEAS researchers gives greater endoscopic optical imaging resolution and sample detail for anatomic pathologists performing diagnostics

Anatomic pathologists and clinical laboratories know that biopsy samples are necessary to diagnose many diseases. But, current endoscopic imaging techniques used by physicians sometimes fail to clearly visualize disease sites. Consequently, biopsies collected during these procedures may make it harder for pathologists and physicians to diagnose certain diseases and health conditions.

Now, a combined team of endoscopic imaging experts at Massachusetts General Hospital (MGH) and flat metalens developers at Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed “a new class of endoscopic imaging catheters—termed nano-optic endoscopes—that overcomes the limitations of current systems.”

That’s according to an article in Nature Photonics that reported on the research team’s study, published in

These nano-optics involved “flat metalenses” that promise to sharpen clarity and increase resolution of endoscopic imaging technology In turn, this contributes to more accurate pathology diagnostics and improve patient outcomes, while furthering the aims of precision medicine.

“Metalenses based on flat optics are a game changing new technology because the control of image distortions necessary for high resolution imaging is straightforward compared to conventional optics, which requires multiple complex shaped lenses,” Federico Capasso, PhD, Robert L. Wallace Professor of Applied Physics and Vinton Hayes Senior Research Fellow in Electrical Engineering at SEAS, and co-senior author of the study paper, told Nature Photonics. “I am confident that this will lead to a new class of optical systems and instruments with a broad range of applications in many areas of science and technology.”

The image above shows a flat metalens taken using a scanning electron microscope. Anatomic pathologists and medical laboratories will benefit from the better quality biopsy specimens collected because of the sharper clarity and increased resolution of endoscopes built with the new nano-optics. (Photo copyright: Harvard SEAS.)

Researchers demonstrated the nano-optic endoscope’s ability to deeply penetrate and capture images at high resolutions in various tissues, including:

  • Swine and sheep airways;
  • Human lung tissue; and,
  • Fruit flesh.

In the human lung tissue, “[T]he researchers were able to clearly identify structures that correspond to fine, irregular glands indicating the presence of adenocarcinoma, the most prominent type of lung cancer,” according to

Improving Endoscopic Imaging through Metalenses

The improved image resolution is due to the flat metalens configuration. “Currently, we are at the mercy of materials that we have no control over to design high-resolution lenses for imaging,” Yao-Wei Huang, PhD, Post-Doctoral Fellow at Harvard’s John A. Paulson School of Engineering and Applied Sciences and co-first author of the paper, told

Yao-Wei Huang, PhD (above), is a Post-Doctoral Fellow at Harvard’s John A. Paulson School of Engineering and Applied Sciences and co-first author of the study paper. “The main advantage of the metalens is that we can design and tailor its specifications to overcome spherical aberrations and astigmatism and achieve very fine focus of the light. As a result, we achieve very high resolution with extended depth of field without the need for complex optical components.” (Photo copyright: Harvard School of Engineering and Applied Sciences.)

The researchers note that current endoscopes using gradient-index (GRIN) lens-prism configurations and angle-polished ball lenses are used in a range of clinical applications due to their basic design. However, this benefit comes with shortfalls. “The ability of the nano-optic endoscope to obtain high-resolution images of sub-surface tissue structures in vivo is likely to increase the clinical utility of OCT [optical coherence tomography] in detection, diagnosis, and monitoring of diseases,” they state in their paper.

“The ability to control other properties of output light, such as the polarization state, enables a host of other applications—implausible to achieve using conventional catheters,” they continue. “Several tissues—such as smooth muscle, collagen (either innate or in fibrosis), and blood vessels—have constituent structures highly organized in one particular direction. Polarization-sensitive imaging can differentiate these structures from surrounding tissue by detecting their innate birefringence and optic axis.”

They further note that nano-optic endoscopes may yield benefits to other endoscopic optical imaging modalities such as confocal endomicroscopy.

Additional clinically-oriented studies will be required to assess how nano-optic endoscopes can elevate the capabilities of endoscopic OCT in examining fine pathological changes in luminal tissues.

Implications for Clinical Laboratories and Pathology Groups

The technology is still in the research stage with more trials needed to confirm the viability and accuracy of the approach. “This preclinical evaluation of the nano-optic endoscope indicated no significant flaws in the design for in vivo endoscopic imaging,” researchers note.

However, should nano-optic catheters gain clearance and change the endoscopy landscape as researchers predict, medical laboratories and pathologists might enjoy higher resolution images with greater information of the sample site—both key components of accurate diagnosis.

“Clinical adoption of many cutting-edge endoscopic microscopy modalities has been hampered due to the difficulty of designing miniature catheters that achieve the same image quality as bulky desktop microscopes,” Melissa Suter, PhD, Assistant Professor of Medicine at MGH and Harvard Medical School (HMS) and co-senior author of the study told Nature Photonics. “The use of nano-optic catheters that incorporate metalenses into their design will likely change the landscape of optical catheter design, resulting in a dramatic increase in the quality, resolution, and functionality of endoscopic microscopy. This will ultimately increase clinical utility by enabling more sophisticated assessment of cell and tissue microstructure in living patients.”

This research project at Massachusetts General Hospital and Harvard John A. Paulson School of Engineering and Applied Sciences is another example of how advances in technologies unrelated to surgical pathology can eventually contribute to improvements in how pathologists diagnose disease and help physicians identify the most promising therapies for their patients.

—Jon Stone

Related Information:

Nano-Optic Endoscope Sees Deep into Tissue at High Resolution

Nano-Optic Endoscope for High-Resolution Optical Coherence Tomography In Vivo

Nano-Optic Endoscope Allows High-Resolution Imaging

High-Resolution Nano-Optic Endoscope for Better Disease Detection