Abstract
In recent years, phenotypic drug screening has achieved renewed prominence, because it can develop drugs for some rare diseases with unknown etiology and without effective therapeutic drugs. Combined with biochip microarray technology, surface plasmon resonance imaging (SPRi) technology based on changes in reflected light intensity has been widely used to analyze interactions between biomolecules, especially for in vitro drug screening. However, changes in reflected light intensity are merely derivative of changes in surface plasmon resonance angles, so current SPRi technology suffers from low accuracy, poor sensitivity, and narrow linear range. In this study, we built an improved SPR microscopic imaging system capable of directly detecting SPR resonance angle (SPR-dip) shifts, with a sensitivity of 8.14 × 10−6 RIU, and a stability less than ± 2 m°. By optimizing the optical path system, the linear correlation coefficient of the system within the scanning range of 3800 m° is 0.9975. Based on this imaging system, we established a reliable screening system for single living mast cell allergy drugs. By developing small molecule microarray chips, we achieved high-throughput screening of 2400 sample points at one time. Our SPR microscopic imaging system integrates the comparative advantages of existing angle-scanning SPRi systems and opens the possibility of new applications in phenotypic drug screening.
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