High-resolution Scanning Surface Plasmon Resonance Microscopy for Imaging of Colorectal Cancer Sensor Array

With the changes of living style and diet habit, the occurrence of colorectal cancer (CRC) has steadily increased in recent years. More than half of new CRC patients are initially diagnosed and received treatments beyond stage II or even III and thus have lower 5-years relative survival percentage due to metastasis or relapse. Thus, it is critical to develop a better tool to assist the clinician for appropriate prognosis of recurrence or prediction of survival rate in different cancer stage or in different tumor site or even to deliver a proper personalized treatment. Multiplex detection of prognostic cancer biomarkers has been an important trend in translational medicine and the grand challenge is to achieve higher detection sensitivity at lower sample volume.
In this thesis, our study was based on the foregoing researches of scanning surface plasmon resonance microscopy (sSPRM) and applied this technique to novel detection of submicron scale protein array. It is a label-free optical sensing method of high resolution and sensitivity. Based on the foregoing system researches on scanning surface plasmon resonance microscopy, we firstly characterized the quality of imaging system with fabricated nano-structure. According to measurement results, the lateral resolution of system was 1 μm and the resolution of surface plasmon resonance angle was 0.0045 degrees, which is equal to 〖10〗^(-4) of effective refractive index changes on thin film measurement. It revealed that this sSPRM can serve as a high sensitivity image-type sensing technique.
At the second part of this thesis, we applied this sSPRM system to cancer biomarker array detection. We used the placental growth factor (PlGF), one of colorectal cancer prognostic biomarkers, as the sensing target. According to the experimental results, compared to the conventional SPR senor chip (gold film), the sensitivity of detection improved 10 folds at low sample concentration (below the 100 pg/mL) by gold array senor chip in submicron scale. The limit of detection was down to the 10 pg/mL in reference to the negative control and the linear range of detection included the prognostic threshold 20.6 pg/mL of placental growth factor. In conclusion, the using of test cost of the sensor array was lower than ELISA method and our detection method can enhance the sensitivity and the detection limit without additional fluorescent label by Au array imaging of SPRM. In the future, we expect that the advantage of sensor array, detecting many prognostic biomarkers by SPRM system, can provide an appropriate prognosis and increase the survival rate of colorectal cancer.