An Implantable Chip for Time Resolved Fluorescence Detection

An Implantable Chip for Time Resolved Fluorescence Detection

Kurvink, J.W.

French, P.J. (mentor)
Margallo Balbás, E. (mentor)

Electrical Engineering, Mathematics and Computer Science

Electronic Instrumentation

Master Thesis

2010-08-30

Photodynamic therapy (PDT) can be used to treat all kinds of (pre-)malignant and non malignant cells, and has some great advantages in comparison with conventional treatments, like radiotherapy and chemotherapy. To be able to perform PDT one needs three things to be present in a cell: photosensitizer, light of a specific wavelength, and oxygen. A photosensitizer is a specially designed drug that that is activated by light of a specific wavelength. When activated, the photosensitizer reacts with oxygen, which leads to cell death. The cell death can occur in two ways: necrosis and apoptosis. A new type of PDT has been introduced recently in the treatment of brain tumors, which is called metronomic PDT (mPDT). The principle of mPDT is similar to that of PDT, but the difference is the length of the treatment. mPDT works with a lower light dose and a longer treatment time compared to conventional PDT. This ensures that the cells dies in a natural way (apoptosis) and do not cause inflammations, which happens in normal PDT. To be able to perform mPDT on a human brain, it is necessary that the treatment can be monitored. For this purpose information on the state of the photosensitizer is necessary. An important aspect of the photosensitizer is the fluorescence, which occurs upon light absorption by the photosensitizer and is related to electronic transition from an excited state to the ground state of the used molecule. From the fluorescence reflection spectrum one can determine the concentration and interaction with cells, as well as localisation and configuration of the photosensitizer. The photosensitizers used for the treatment have a lifetime from 3.5ns to 10ns. To measure the lifetime of the photosensitizer we need to be able to reconstruct the exponential decay of the fluorescence reflection spectrum. In order to do this we use a LED to excite the photosensitizer and a photodiode for detection of the fluorescence reflection spectrum. We integrate the photocurrent on the parasitic capacitor of the photodiode, to make sure the system is fast. When the signal is integrated once, it holds no usable information other than the total charge integrated. For this purpose a tune-able delay circuit has been designed that can delay the beginning of the measurement, which allows us to change the integration window. If we now integrate the same signal several times, while changing the starting time for each integration, we can reconstruct the exponential decay of the fluorescence reflection spectrum. The designed chip houses the timing circuit for the tune-able delay, as well as a photodiode for light detection, and an amplifier to amplify the signal enough for readout with an AD-converter. There is also space for a LED on the chip, which is also controlled by the timing circuit to ensure correct on and off switching of the LED. The chip is designed in such a way that it can work with a external light source as well. The measurements are done without a photosensitizer because they are to expansive to use before proper testing of the chips has been completed. Instead of a photosensitizer the switching behaviour of the LED is used to determine the chips behaviour. The delay circuit works as designed. However we where not able to measure the delays that are created. We where able to show that the chip functions in the a way that is similar to what is expected.

Time Resolved Fluorescence
Fluorescence

http://resolver.tudelft.nl/uuid:ca67021d-9277-4366-98cf-9d33c7e04479

2010-08-31

Student theses

master thesis

(c) 2010 Kurvink, J.W.