Unmanned reaction condition experiments for small molecule drugs jointly developed by Shimadzu and Astellas

Shimadzu Corporation, in collaboration with Astellas Pharma Inc., has developed "AtmosOrchestra," a robotic High-Throughput Experimentation (HTE) automation device designed for screening reaction conditions of small and medium molecule pharmaceuticals. By fully automating complex sample synthesis steps, the device achieves rapid and efficient screening experiments, supporting the search for optimal synthesis conditions for small and medium molecule drugs. The device was introduced to Astellas Pharma's Tsukuba Research Center in late April.

AtmosOrchestra automates a complicated sample synthesis step at the early stage of drug development by utilizing industrial robots and Shimadzu's liquid dispensing devices in which liquid is injected into multiple containers. It is a specially designed machine that achieves complete unmanned operation of the entire process. Through "Analytical Transformation" (AX), an analytical process innovation powered by AI and robotics, Shimadzu has been aiming to automate laboratory workflows, and this joint development is part of these efforts.

HTE is a methodology that uses robotics and AI to rapidly and concurrently conduct compound exploration in drug discovery and the optimization of reaction conditions in process chemistry.

CMC (abbreviation of chemistry, manufacturing, and controls) research is indispensable in the steps from small molecule drug discovery to stable supply. In CMC research, screening experiments must be repeatedly performed to find the optimal synthesis conditions from a vast combination of factors, such as the types and ratios of raw materials used in the synthesis, reaction temperatures, and stirring conditions.

In recent years, because the "analysis" and "evaluation" stages in the cycle of searching for optimal conditions have become more efficient, the manual "experimentation" stage has increasingly become the bottleneck of the exploratory cycle.

The experimental workflow automated by AtmosOrchestra consists of the following steps: dispensing (injecting the sample solution into a dedicated plate), solvent drying (drying the solution on the dedicated plate using a centrifugal concentrator), dispensing (adding another solution required for the reaction into the dedicated plate), reaction (heating with a volatile-preventive lid while stirring and maintaining temperature to facilitate the reaction), and solvent drying (drying the solution inside the dedicated plate once again).

Screening experiments deal with compounds that are sensitive to oxidation and moisture absorption. The inside of the reaction chamber is purged with nitrogen during operation of the device to maintain a low-oxygen, low-humidity environment. Variability is also minimized through precise time control between steps and the prevention of solvent volatilization via sealing with dedicated caps. The functional modules executing each step and the robotic arms are enclosed within the reaction chamber. Furthermore, reagents can be supplied and completed samples can be recovered via pass boxes installed at the front and back of the reaction chamber, supporting efficient testing execution.

Inside the chamber, eight dedicated heating and stirring modules and three dispensing devices allow for the processing of up to 768 samples (96-specimen vials × 8 dedicated plates) in a single run. Automating long-duration reaction experiments enables them to run unattended during nights and days-off, contributing to labor savings and enhanced throughput. Furthermore, screening to find optimal conditions requires sample synthesis based on complex parameter configurations.

At the start of a screening experiment, using Shimadzu's control software product, "LabSolutions DB," simplifies the parameter setup while securing sample traceability through features such as account management and automated report generation.