Laser scanning microscope for fast cancer cell detection

Researchers at Germany’s Fraunhofer-Gesellschaft have developed a technology for quickly determining whether a tumour has been fully removed — before the patient even leaves the operating theatre. Using a combination of laser scanning microscopy and fluorescent tumour markers, doctors can detect any remaining cancer cells immediately after an operation.

Surgically removing a tumour is a delicate process. The cancerous tissue must be removed in its entirety, with great precision and as few incisions as possible. Afterward, the surgeon must ask themselves a number of questions. Were all the cancerous cells completely removed? Did the removal damage the surrounding tissue? With brain tumours in particular, it is important to remove as few healthy nerve cells as possible.

Now, Fraunhofer researchers working in the LSC-Onco (Laser Scanning Oncology) project claim to have found a quick, reliable solution to this problem by combining laser scanning microscopes and fluorescent tumour markers. Using the microscope, doctors can examine the tissue surrounding the area the tumour was removed from, without even leaving the operating theatre.

“A fluorescent marker applied beforehand allows doctors to see any cancer cells that may be left behind after the incision,” explained Michael Scholles, Head of the Fraunhofer Center for Microelectronic and Optical Systems for Biomedicine MEOS. “Then these cells can be completely removed, with great precision.”

The technology was developed at the Fraunhofer Center in Erfurt, where MEOS works on key technologies in the fields of life sciences, microelectronics, optics and photonics. The project involved researchers from the Fraunhofer Institute for Photonic Microsystems IPMS in Dresden and the Fraunhofer Institute for Cell Therapy and Immunology IZI in Leipzig.

In the LSC-Onco project, experts from Fraunhofer IPMS developed the concept of a laser scanning microscope further, using a microscanner mirror manufactured with MEMS (micro-electro-mechanical systems) technology. Inside the microscope, the mirror oscillates at a rate of several thousand times per second, directing blue laser light with a wavelength of 488 nm over the entire image field point by point. The mirror simultaneously directs the fluorescent light emitted by the tissue towards a highly sensitive photodetector. The signals from the photodetector can then be used to construct a two-dimensional image. Images can also be recorded on different planes, so that tumour cells beneath the surface also become visible.

“This means that, for the first time, a powerful, portable laser scanning microscope that can be positioned right next to the patient in the operating theatre is a feasible reality,” Scholles said.

The laser scanning microscope from the LSC-Onco project is so small and compact that it can be used to examine patients right on the operating table. Image ©Fraunhofer.

Fluorescent tumour markers

Before the microscope can detect cancer cells, the cells themselves must first be marked. Researchers from Fraunhofer IZI used their biomedical expertise to develop a fluorescent tumour marker liquid that makes cancer cells glow beneath the microscope. The team from Fraunhofer IZI developed the markers for use on brain and skin tumours and are currently investigating whether other types of tumours will react similarly. The Helios Hospital Erfurt provided the tissue samples necessary for developing the tumour markers, with the consent of patients.

After the tumour is removed, the tumour marker is applied to the surrounding tissue and the laser scanning microscope is positioned directly above the wound. When the microscope’s blue laser beam encounters healthy cells, the reflected light is blocked by dichroic filters, which have the ability to pass only specific wavelengths. As a result, the image on the microscope display stays black for those cells. However, if the blue laser encounters cancerous cells, the tumour marker emits a fluorescent green. This light passes through the dichroic filters and appears on the display as a green dot or patch. The resolution of the system is so high that even individual cancer cells can be detected and shown on the display.

“It only takes a few seconds to examine the operating field with the laser scanning microscope,” Scholles said. By referring to the image on the display, doctors can cleanly remove any remaining cancer cells (normally found at the edge of the wound) in their entirety, all without damaging the healthy tissue.

Improving chances of recovery

When compared to current practices in oncological surgery, LSC-Onco represents a huge step forward. Prior to this development, surgeons have generally taken tissue samples from the edges of the wound following the removal of a tumour and sent these samples to a hospital laboratory. After a few minutes’ wait, a diagnosis would be delivered as to whether the sample cells were cancerous. If so, the surgeon would then have to cut away more tissue. This method is very time-consuming, which adds to the strain on the patient undergoing the operation.

“With LSC-Onco, all these steps can be carried out in one go during the operation, and what’s more, the precision is much greater,” Scholles said. “It also protects the surrounding tissue, because you can see exactly where the healthy tissue starts on the microscope display. And now, waiting for lab tests results is a thing of the past.”

As a result, operations can be completed faster and patients can be taken off anaesthetic. The technology also improves the patient’s chances of a complete and permanent recovery, as it ensures clean removal of all cancer cells.

“We have already received extremely positive feedback from doctors,” Scholles said. Now, the project team wants to take the next step and bring LSC-Onco into medical practice.

Top image shows a tumour section recorded with the LSC-Onco microscope. The fluorescent green area indicates cancer cells. Image ©Fraunhofer.

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