Persistent identifiers (PID) to identify digital representations of physical specimens in natural science collections (i.e., digital specimens) unambiguously and uniquely on the Internet are one of the mechanisms for digitally transforming collections-based science. Digital Specimen PIDs contribute to building and maintaining long-term community trust in the accuracy and authenticity of the scientific data to be managed and presented by the Distributed System of Scientific Collections (DiSSCo) research infrastructure planned in Europe to commence implementation in 2024. Not only are such PIDs valid over the very long timescales common in the heritage sector but they can also transcend changes in underlying technologies of their implementation. They are part of the mechanism for widening access to natural science collections. DiSSCo technical experts previously selected the Handle System as the choice to meet core PID requirements. Using a two-step approach, this options appraisal captures, characterises and analyses different alternative Handle-based PID schemes and the possible operational modes of use. In a first step a weighting and ranking the options has been applied followed by a structured qualitative assessment of social and technical compliance across several assessment dimensions: levels of scalability, community trust, persistence, governance, appropriateness of the scheme and suitability for future global adoption. The results are discussed in relation to branding, community perceptions and global context to determine a preferred PID scheme for DiSSCo that also has potential for adoption and acceptance globally. DiSSCo will adopt a ‘driven-by DOI’ persistent identifier (PID) scheme customised with natural sciences community characteristics. Establishing a new Registration Agency in collaboration with the International DOI Foundation is a practical way forward to support the FAIR (findable, accessible interoperable, reusable) data architecture of DiSSCo research infrastructure. This approach is compatible with the policies of the European Open Science Cloud (EOSC) and is aligned to existing practices across the global community of natural science collections.