The oblique-incidence reflectivity difference (OI-RD) microscope is a label-free detection system for microarrays that has many successful applications in high throughput drug screening. The increase and optimization of the detection speed of the OI-RD microscope will enable it to be a potential ultra-high throughput screening tool. This work presents a series of optimization methods that can significantly reduce the time to scan an OI-RD image. The wait time for the lock-in amplifier was decreased by the proper selection of the time constant and development of a new electronic amplifier. In addition, the time for the software to acquire data and for translation stage movement was also minimized. As a result, the detection speed of the OI-RD microscope is 10 times faster than before, making the OI-RD microscope suitable for ultra-high throughput screening applications.