Before I heard of Portable Thunderbird I tried -- successfully but not enough for me -- to do this myself using mainstream Thunderbird and just inputting the removable drive as the installation directory.
This was a Windows 10 Dell laptop that had had the previous installation of Thunderbird on its C: drive deleted, including ALL Mozilla/Thunderbird directories. The removable drive (D:) was an SDHC.
The new Thunderbird was 78.2.2 and the custom install settings were:
Install Location D:\Mozilla Thunderbird\
Install Maintenance Service