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The pharmaceutical manufacturing industry has long struggled with the issue of monitoring the characteristics of a drying mixture, a critical step in producing medication and chemical compounds. At present, there are two noninvasive characterization approaches that are typically used: A sample is either imaged and individual particles are counted, or researchers use a scattered light to estimate the particle size distribution (PSD). The former is time-intensive and leads to increased waste, making the latter a more attractive option.

In recent years, MIT engineers and researchers developed a physics and machine learning-based scattered light approach that has been shown to improve manufacturing processes for pharmaceutical pills and powders, increasing efficiency and accuracy and resulting in fewer failed batches of products. A new open-access paper, “Non-invasive estimation of the powder size distribution from a single speckle image,” available in the journal Light: Science & Application, expands on this work, introducing an even faster approach. 

“Understanding the behavior of scattered light is one of the most important topics in optics,” says Qihang Zhang PhD ’23, an associate researcher at Tsinghua University. “By making progress in analyzing scattered light, we also invented a useful tool for the pharmaceutical industry. Locating the pain point and solving it by investigating the fundamental rule is the most exciting thing to the research team.”

The paper proposes a new PSD estimation method, based on pupil engineering, that reduces the number of frames needed for analysis. “Our learning-based model can estimate the powder size distribution from a single snapshot speckle image, consequently reducing the reconstruction time from 15 seconds to a mere 0.25 seconds,” the researchers explain.

“Our main contribution in this work is accelerating a particle size detection method by 60 times, with a collective optimization of both algorithm and hardware,” says Zhang. “This high-speed probe is capable to detect the size evolution in fast dynamical systems, providing a platform to study models of processes in pharmaceutical industry including drying, mixing and blending.”

The technique offers a low-cost, noninvasive particle size probe by collecting back-scattered light from powder surfaces. The compact and portable prototype is compatible with most of drying systems in the market, as long as there is an observation window. This online measurement approach may help control manufacturing processes, improving efficiency and product quality. Further, the previous lack of online monitoring prevented systematical study of dynamical models in manufacturing processes. This probe could bring a new platform to carry out series research and modeling for the particle size evolution.

This work, a successful collaboration between physicists and engineers, is generated from the MIT-Takeda program. Collaborators are affiliated with three MIT departments: Mechanical Engineering, Chemical Engineering, and Electrical Engineering and Computer Science. George Barbastathis, professor of mechanical engineering at MIT, is the article’s senior author.