Breaking Down Barriers to Protein Sequencing

Protein and proteomic sequencing is an important part of understanding how organisms operate in health and disease. However, protein sequencing technology has lagged behind next-generation nucleic acid sequencing, largely due to the fact that proteins, unlike nucleic acids, cannot be easily amplified.¹ Novel strategies and technologies are aimed at making higher-resolution protein sequencing more streamlined and accessible.

         

To study proteins, researchers commonly turn to mass spectrometry (MS) and antibody-based strategies such as western blotting and enzyme-linked immunosorbent assays (ELISA).¹ However, these techniques have their drawbacks. MS offers high-resolution protein characterization of known and unknown peptides, but the method is costly in terms of expensive instrumentation and the time required to learn and master its use. Indeed, many scientists choose to outsource their MS experiments to dedicated centers rather than maintain in-house instruments. By contrast, antibody-based strategies such as ELISA or immunohistochemistry are easily accessible and highly flexible but offer low resolution and can only detect known targets since each target must be matched with its own specific probe. 

The development of next-generation protein sequencing technology is a priority. Scientists recently established an approach where peptides are immobilized in nanoscale reaction chambers on semiconductor chips.² Here, N-terminal amino acids—exposed one-by-one by aminopeptidases—can be detected in parallel with dye-labeled recognizers in real time. This method drives the Platinum^™ Next-generation Protein Sequencer from Quantum-Si, a benchtop device capable of interrogating proteoforms, post-translational modifications, and low-abundance proteins at single-molecule resolution. This sequencer’s workflow takes less than three hours of hands-on time, and data analysis does not require bioinformatics expertise. Instruments like this make single-molecule protein sequencing possible for any lab anywhere.