In 1844, he obtained the Huishoudelyk Woordboek", a Dutch translation of Nöel Chomel's encyclopedia, from which Sakuma learned how to make glass, and then magnets, thermometers, cameras and telescopes.

After the Bakufu ordered Japanese translations of the Military History of the Qing dynasty (聖武記, Shèngwu Ji) and the Illustrated Treatise on the Maritime Kingdoms written by Chinese scholar Wei Yuan (1794–1857), Sakuma was struck by the similarities in their ideas in defending against the west.

[1] His writing brought some fame, and he became the teacher of several future leaders of modernization (Yoshida Shōin, Katsu Kaishū, Sakamoto Ryōma, Nakaoka Shintarō, Hashimoto Sanai, Katō Hiroyuki, Nishimura Shigeki, Yamamoto Kakuma).

In 1853, when Yoshida Shōin was convicted for attempting to stow away on one of Perry's ships, Sakuma was also sentenced by association to house arrest (蟄居), which he endured for 9 years.

During the arrest, he continued to study Western sciences, and developed various electric machines based on the Elekiter and the Daniell battery, Japan's first seismometer, as well as improvements to guns.

He was on a mission to meet with a member of the imperial family to explain his ideas and to seek the permission of Emperor Kōmei to legally open Japanese ports to foreign trade.

On August 12, 1864, as he reached the Sanjō-Kiyamachi district of Kyoto, his retainers, a considerable distance behind and making no effort to catch up with him, failed to notice that two mysterious men were following him on foot.

His son Miura Keinosuke [jp] (三浦啓之助), real name Sakuma Kakujirō, was a member of the Shinsengumi, which he joined in September 1864 to avenge his father's death.