He very soon abandoned the study of law in order to devote himself, under the direction of Prof. Paoli and Abbot Pacchiano, exclusively to mathematics and the natural sciences.

At their urgent suggestion Santini's family, especially his uncle, made great sacrifices to enable him to continue his studies in Milan (1805–1806) under Barnaba Oriani, Cesaris, and Francesco Carlini.

Constantly striving to equip this institute in accordance with the latest requirements of science, he installed in 1823 a new Utzschneider equatorial, and in 1837 a new meridian circle.

With these last he began at once to make zonal observations for a catalogue of stars between declination +10° and -10°, an undertaking which he carried out on a large scale, and which he, with the aid of his assistant, Trettenero, completed in 1857, after ten years of work.

In 1828 appeared his Teorica degli Stromenti Ottici, also published in Padua, in which he explains by means of simple formulas the construction of the different kinds of telescopes, microscopes etc.

A number of his dissertations on geodetic and astronomic subjects appeared in the annals of learned associations, in the Correspondence du Baron de Zach, Astronomische Nachrichten, etc.