Medical Imaging

Each year, around 500,000 people in Germany are diagnosed with cancer. While diagnostic tools and treatment methods are continually improving, surgeons still face a major challenge: determining in real time whether a tumor has been completely removed during surgery. Currently, it is standard practice to extract tissue samples from the resection margin and send them to pathology for analysis - a process that typically takes up to 20 minutes.

What’s needed is a fast, reliable, and on-site solution that can be used directly in the operating room. To meet this demand, researchers from Fraunhofer IPMS and Fraunhofer IZI have developed a new confocal laser scanning microscope for intraoperative tumor diagnostics.

Differentiating Tumor from Healthy Tissue in Real Time

A key challenge in tumor surgery is clearly distinguishing between healthy and cancerous tissue. The goal is to achieve tumor-free resection margins while preserving as much healthy tissue as possible - a critical requirement especially in sensitive areas such as the brain.

Current intraoperative diagnostic methods such as histology are limited: they take time, may not work on certain tissue types like bone, and typically do not provide 3D visualization of tumor margins. This has created a strong need for a rapid optical method that can reliably differentiate tissue types during surgery.

MEMS-Based Confocal Microscopy with Fluorescent Tumor Markers

To address this need, Fraunhofer IPMS and Fraunhofer IZI have developed a MEMS-based confocal laser scanning microscope combined with a fluorescent antibody staining technique for tumor cells. The system is designed to identify tumor boundaries with high spatial precision, aiding surgeons in preserving critical structures like brain tissue and arteries.

The process begins by staining the tumor tissue with fluorescence-labeled antibodies, developed by Fraunhofer IZI. Then, the microscope, which is equipped with a MEMS scanning mirror from Fraunhofer IPMS, captures real-time images of the tissue surface. The mirror deflects light in both x and y directions to produce live, high-resolution images.

Key technical specifications:

• Lateral resolution: < 1.0 μm
• Field of view: 200 x 200 μm² (960 x 960 pixels)
• Z-axis imaging: 2000 μm range, 5 nm step size

First Demonstrator and Next Steps

In 2021, a functional demonstrator of the microscope was successfully tested at the Fraunhofer Center MEOS in Erfurt, using tissue samples provided by clinical partner Helios Klinikum Erfurt.

Looking ahead, future developments will include:

• AI-assisted detection of tumor margins
• Robotic integration to support surgical workflows
• System adaptation for use in clinical settings

This technology represents a significant step toward real-time, image-guided tumor surgery, improving patient outcomes and reducing surgical risk.

Ultrasound imaging (sonography) is a well-established technique in medical diagnostics and industrial measurement technology. Central to these systems are ultrasound transducer arrays, which are responsible for generating and receiving acoustic signals.

Today, most ultrasound arrays in medical systems use piezoelectric ceramic materials, especially lead zirconate titanate (PZT). These rely on the inverse piezoelectric effect to generate mechanical vibrations. While effective, PZT-based solutions come with several limitations:

• High manufacturing costs for high-frequency or air-coupled arrays
• Complex fabrication processes
• Use of toxic materials that are not RoHS-compliant

CMUTs: Capacitive Micromachined Ultrasound Transducers

Capacitive micromachined ultrasound transducers (CMUTs) offer a promising alternative. Based on MEMS fabrication techniques, CMUTs allow for cost-effective production and enable a wide range of applications, especially in miniaturized and invasive scenarios such as intravascular ultrasound (IVUS).

Key Advantages of CMUT Technology

Research and development results show that CMUTs are well-suited for high-frequency, high-resolution ultrasound imaging. Key benefits include:

• Very high acoustic bandwidth
• Extremely low mechanical coupling between elements
• Adaptability for operation in water and air
• Integration with electronic components (e.g., ASICs) on a single chip
• Non-toxic materials, ensuring full RoHS compliance

Moreover, the high bandwidth and low crosstalk between elements are essential for image quality comparable to conventional PZT-based systems. The high level of integration enabled by MEMS technology also allows on-chip signal processing, resulting in compact designs and flat, media-contacting surfaces through monolithic bonding between the sensor and readout electronics.

This enables the development of the next generation of ultrasound devices - more compact, more sustainable, and ready for future diagnostic and industrial needs.

Confocal fluorescence laser scanning microscopy is a powerful imaging technique that irradiates samples point-by-point and measures the emitted fluorescence signal with high precision. This advanced technology enables the capture of high-resolution horizontal sectional images as well as the creation of accurate 3D models of structured surfaces and fluorescent samples. It plays a crucial role in biological research, medical diagnostics, and industrial quality assurance.

Traditional confocal fluorescence microscopes tend to be large, complex, and expensive, limiting their use to specialized research laboratories. Addressing these challenges, Fraunhofer IPMS has developed a compact, robust, and portable MEMS-based fluorescence laser scanning microscope that uses standard optical components to deliver excellent imaging performance in a small form factor.

The core innovation lies in the integration of a high-precision 2D MEMS microscanning mirror, developed in-house, which enables fast and accurate laser beam steering. This technology makes the microscope ideal for on-site applications, including field research, point-of-care diagnostics, and industrial inspection.

Key benefits of Fraunhofer IPMS technology:

• High-resolution 3D fluorescence imaging
• Compact and portable design for mobile use
• Cost-effective alternative to traditional stationary systems
• Versatility for applications in medical, biological, and industrial sectors

Project MicroFlow aims to develop a compact, novel measurement system for precise, independent, and practical monitoring of microperfusion - the blood flow in organs and tissues.

Core Technology: CMOS-Integrated Sensor with Optoelectronic Approach

At the heart of the system is a CMOS-integrated sensor that combines optical and mechanical measurement methods. This sensor can be integrated into wearable clothing and enables secure, energy-efficient data transmission via DECT NR+.

Applications and Benefits

The system is designed to improve the diagnosis of microcirculation disorders and the monitoring of patients with cardiovascular, metabolic, and vascular diseases, severe infections, or post-surgery recovery. Additionally, the technology offers applications in ophthalmology and ear, nose, and throat (ENT) medicine.

Proof-of-Concept and Development

Fraunhofer IPMS and TU Dresden have successfully demonstrated the detection of capillary refill time using an optoelectronic method in a proof-of-concept project. Building on this, an application-oriented sensor is now being developed to serve as the foundation for innovative medical technology products.

Future Outlook

Planned next steps include initial patient studies and expanding applications into leisure and sports to enable microperfusion monitoring beyond clinical settings.