Over the past two decades, tremendous progress has been made in scientific research on optical label-free biosensing devices, including plasmonic and optical resonators, waveguides and meta-structures. Now it is time to combine the advanced device technologies with real world biosensing applications and find industrial breakthroughs. At this point, it is very important for the device research community to form a correct and common view about the true capabilities and performance limits of these devices, and about the key technical challenges in our way to the desired applications. In this paper, we focus on instructing how to measure low concentration biomolecule samples convincingly and support limit-of-detection (LOD) claims. We will first comment on the core values and pitfalls of this research area, and briefly review the fundamental physical principles. Then after elaborating on the biomolecule interaction process and the interference factors, we provide a checklist of the essential points and the proper practices for measuring low concentration biomolecule samples and supporting LOD claims.