BACKGROUND INTRODUCTION

Drug screening is a step in the modern drug development process to test and obtain specific physiologically active compounds. It refers to the process of selecting compounds with higher activity for a specific target from a large number of compounds or new compounds through standardized experimental methods. It is a necessary process for the development of clinical new drugs.

With the emergence of high-throughput methods of genomics and synthetic chemistry, drug screeners are faced with more and more new targets or potential effective ingredients. High-throughput screening has emerged in this context. A high-throughput drug screening system includes micro and semi-micro pharmacological experiment models, sample library management systems, automated experimental operating systems, high-sensitivity detection systems, and data acquisition and processing systems. The operation of these systems ensures that the screening system can be operated in parallel Search for a large number of candidate compounds.

Ogilvy & Mather provides automated experimental operating systems for high-throughput drug screening systems, and provides solutions for screening models at the biochemical and cellular levels of pharmaceutical companies.

CASE SHARING

In the field of new drug screening, cisbio biostays' patented technology htrf (homogeneous time-resolved fluorescence) is widely used in major pharmaceutical enterprises, drug research institutes and new drug screening centers around the world. Htrf, in short, is a wash free ELISA that combines fluorescence resonance energy transfer (FRET) and time-resolved fluorescence (TRF, Time-resolved floorescence) only needs three steps: adding liquid, incubation and reading board, which avoids the complicated and variable washing steps. It is not only easy to operate, but also more stable and reliable.

In recent years, PD-1 / PD-L1 immunosuppressive checkpoint inhibitor, as a new type of cancer immunotherapy, has achieved amazing results in a variety of cancer treatment. The case we selected is to use htrf technology to screen PD-1 / PD-L1 inhibitors. The experimental principle is shown in Figure 1. PD-L1 and PD1 fused tag1 and tag2 respectively, which were recognized by anti-tag1 and anti-tag2 respectively. Because of the donor fluorescent dye EU and acceptor fluorescent dye xl665 labeled with htrf on the antibody, when PD-L1 and PD1 are close and combined, the fluorescence resonance excited by EU is transferred to xl665, which makes xl665 emit fluorescence, and thus detected.

When PD-1 / PD-L1 inhibitors exist, they will block the binding of tag1-pd-l1 protein to tag2-pd-1, thus affecting the fluorescence signal intensity of xl665.

Screening experiment steps

Automation solutions

⬛ According to the experimental steps, develop the automation scheme, and the host model is as follows:


⬛ AMTK LH1406Table layout of multifunctional liquid treatment workstation


Analysis of experimental results

⬛ Comparison of IC50 between automatic filling and manual operation





⬛ Consistency analysis of automatic filling and manual operation


⬛ Conclusion: the AMTK lh1406 multi-functional liquid processing workstation has realized the complete automation of the operation process, and the performance indexes have reached the requirements.