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Portfolio Company Spotlight

RedShiftBio Finds a Better Way to Visualize Biomolecules  

FEBRUARY 2023 – 

For proteins and other biomolecules, structure is everything. A molecule’s form often dictates its function, making analyzing biomolecular structures a critical task for developing biologic drugs. Both science and the FDA demand it. 


Life sciences companies and academic labs spend a lot of time and effort interrogating protein structures; however, RedShiftBio would rather they didn’t have to work quite so hard for structural information. The company has created a platform that combines microfluidic modulation spectroscopy (MMS) and quantum cascade lasers to generate precise, ultra-sensitive molecular structure measurements. 


“Accurate structural data is a must-have,” said Wouter Meuleman, Partner at Illumina Ventures. “Structure has a profound impact on a large molecule’s safety, efficacy, stability, and more. RedShiftBio has developed a groundbreaking technology that makes producing this essential structural information faster and easier, and that’s a huge win for everyone.” 

Eliminating the Background Noise Problem

Measuring biomolecular structures is hard because they live in liquids – large molecules surrounded by small molecules. In addition, these media contain salts and other ingredients to increase the drug’s stability and safety. Any effort to understand biomolecular structures must somehow subtract that background information, which can dwarf the protein’s signature.  


Until RedShiftBio came along with MMS, researchers often relied on two techniques: Fourier transform infrared (FTIR) and circular dichroism (CD). With FTIR, any water in the sample reads as a huge infrared signal, and researchers must subtract that signal manually. CD is poorly suited for higher protein concentrations and susceptible to interference from buffers and other media. 


“These methods are slow, imprecise and pose a significant drug development bottleneck,” said RedShiftBio’s Chief Executive Officer Julien Bradley. “They also require substantial manual intervention and provide relatively poor sensitivity.” 


MMS addresses these limitations, enabling structural analyses over wide concentration ranges and complex formulations. The technology uses a mid-infrared quantum cascade laser, which is 1,000 times brighter than conventional FTIR. In addition, MMS features two microfluidic streams – the biomolecule in a buffer and the buffer alone. The laser rapidly alternates between the two streams to gain the most timely and accurate information about the buffer’s molecular traits, which are automatically deleted from the biomolecule’s readout.  


“We are using the quantum cascade laser to create a spectral fingerprint,” said Bradley. “Five times per second, the flow cell switches between sample and reference. It’s almost like putting an object on a scale and taring out the weight of the container. That gives us a lot of information about the protein, including its primary structure and how it's folded.” 


MMS Applications  

Companies must ensure their molecules – biologics, biosimilars, monoclonal antibodies, antibody-drug conjugates, etc. – are structurally consistent. MMS gives them a fast and accurate tool to make that happen. 


“We’ve seen significant growth in formulation,” said Bradley. “A company discovers several candidate molecules and needs to figure out which one can become a product. Can it be formulated so it’s stable? If the molecule is stressed by temperature or pH over time, does it maintain the same structure? MMS answers these questions in a fast and automated way.” 


RedShiftBio’s technology could also play a role in mRNA therapeutics. Like proteins, mRNA drugs must be fully characterized before they can move forward. Another promising area is cell and gene therapy, particularly adeno-associated viruses (AAVs), which are difficult to characterize.  


“We are helping our customers see things they simply could not see before because it was too challenging or they didn't have the sensitivity or resolution,” said Bradley. “This technology opens doors in both drug development and academic research, giving labs a much better discovery tool.”   

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