Implantierbares optisches Sensorsystem zur Überwachung von rezidivierenden Glioblastomen

Despite combination therapy, glioblastoma patients face poor prognoses and eventual relapse, commonly at the site of resection. With conventional MRI surveillance, histologic changes might be overlooked or misinterpreted. We propose an implantable system that provides accurate continuous monitoring of recurrence through the optical detection of fluorescently labeled cancer cells.

A 5ALA-fluorescence detecting precision sensor was designed and manufactured. To evaluate the sensor's ability to detect fluorescence in cancerous tissue, human glioblastoma cells from the BTSC322 and NCH421K cell lines were employed. These cells were cultured in 3D spheroid models and encapsulated within extracellular matrix domes. The samples were incubated with two concentrations of 5-ALA (0.1mM; 1mM) for 8 hours prior to measurements. Further, to devise an extracorporeal wireless energy supply for the implant, electromagnetic field simulations were conducted with three transmitter and receiver coil configurations. The most promising design was then implemented in a prototype energy transmission system, manufactured and subjected to energy transfer tests through animal tissue. Lastly, a comprehensive bi-modal implantable system was designed.

All 5-ALA-treated samples were successfully detected by the sensor, with effectively suppressed interfering signals such as excitation light. The relationship between 5-ALA concentration and the measured signal could be accurately modeled for both cell lines using the power law, proportional to the forth root of the 5-ALA concentration (linear regression, β = 567.4 & 1293.3 for BTSC322 and NCH421K respectively, CI: 482.2 – 652.5 & 805.6 – 1781.1, R2 = 0.99 & 0.95, p < 0.01). Energy transfer simulations showed maximum energy transfer efficiencies of 0.7, 0.8 and 0.47 for the three alternative coil configurations. The configuration featuring a 4-layer implantable receiver coil and an external transceiver flat coil was fabricated and achieved an efficiency of 0.6 at the resonant frequency during testing.

The examined prototype successfully detected samples with human cancer cells even at dimensions of a few millimeters. The proposed monitoring system could enable early detection of recurrences and contribute to the optimization of treatment for GBM patients.