Figure 1: Fluorescence light microscopy images of endoscopic spraying attempts with different nanoparticle concentrations (dye: FUTC).

During the course of minimally invasive tumor resection, it is often difficult for the surgeon to clearly distinguish between healthy and sick tissue on the endoscopic image. Furthermore, the surgeon does not perceive the haptic and tactile sensations needed to evaluate the tissue by means of palpation. The use of navigation systems to localize the tumor usually fails due to the presence, quality, accuracy or the informational content of the image data. Therefore, a tumor sample is usually taken during surgery and given to the pathologist. This procedure can take up to one-half hour and requires that the operation be “put on hold” for this period of time. However, a final laboratory examination can take significantly longer. To minimize the risk, the surgeon supplements the expertise of the pathologist and a mutual assessment of the tissue status is usually made. This decision is extremely risky, for example, if the partial resection of a tissue or an entire organ depends on it. Quality control of the resection margins is so far not possible by any means. Thus, the necessity of resecting large volumes remains for reasons of safety. Project C-VIS concerns an alternative method which in a short period of time can directly help visualize the tumor tissue in the body.

Making tumor tissue visible with nanoparticles

Figure 2: REM images of a pretreated sample after spraying with nanoparticles and subsequent rinsing steps. It is clear that the nanoparticles only attach to the intended locations. From left to right, magnifications of 500; 2,500 and 25,000 are shown.

The C-VIS method is based on the property of modified nanoparticles attaching to tumor cells, but not to healthy cells. To this purpose, we at Fraunhofer IGB are producing nanoparticle hybrid systems consisting of synthetic nanoparticles and biologically active proteins. For example, these biomimetic constructs are able to detect tumor tissue and distinguish it from healthy tissue. The nanoparticles are produced by means of colloid chemistry and are provided with surface functions that are complementary to those of the introduced protein reactivities. In other words, they can form bonds with the anchor sites. The protein constructs are then conjugated with the nanoparticles in a chemically mild and thus protective reaction.



Unambiguous marking during the operation

Figure 3: The progress of an operation is shown: 1. Positioning of the endoscope, 2. Spraying of the nanoparticles: The marked TNF-functionalized silica nanoparticles bind to cells.

During surgery, these particles should be sprayed through the endoscope and onto the tissue surface or the resection margins. The particles which have previously been treated with fluorescent markers are then stimulated by a light source of the appropriate wavelength and thus made visible in contrast to the healthy tissue. On the video endoscope image the surgeon can see the stimulated and passive surface segments in vivo. With this information, he can treat the tumor and the resection margins in a targeted manner. In this collaborative research project the Fraunhofer IPA is working on the design of this novel endoscope.


The C-VIS project is an alternative or complementary solution to computer-assisted diagnosis (CAD) which presently focuses on approaches using technical analysis software. After an evaluation of the spraying processes subsequently with tissue, preclinical studies which will examine the procedure for its suitability in the actual practice of medicine are still outstanding. If these prove successful, the next step will focus on developing different nanoparticles to detect specific tumors, investigating solutions for automatic image evaluation and pursuing the options for precise spatial localization of the tumor. In the future C-VIS could be integrated into an automated resection procedure such as one that uses a robot system. 

Project partner

Fraunhofer Institute for Production and Automation IPA, Stuttgart