Every year, nearly 100 million people in the US receive flu vaccines, accounting for a $2
billion market. Due to antigenic drift, new flu vaccines need to be produced every year under an
extremely tight timeline. Delays in manufacturing have severe healthcare consequences.
A major rate-limiting step in the flu vaccine manufacturing process is the assessment of
vaccine potency. The single radial immunodiffusion (SRD) assay is the current gold standard
method, but suffers from several limitations: 1) the SRD reagents need to be freshly prepared
every year by immunizing sheep, which takes multiple months and presents a bottleneck when
the vaccine is most needed. 2) SRD is labor-intensive and requires trained personnel, and takes
several days to complete; 3) SRD was originally validated against inactivated vaccine; growing
evidence suggests it may not be suitable for novel vaccines. In result, both recent EMA
guidelines and a joint workshop by FDA and WHO concluded that alternative methods should
be developed to address these limitations, and that an ideal assay should be “low cost, not
labor-intensive, high throughput, high specificity, stability-indicating, and indicative of antigenic
structure and vaccine efficacy”.
We propose to solve this problem by developing an aptamer-based multiplex
electrochemical biosensor. Similar to SRD, our sensor is low-cost, highly specific, and can
assess vaccine stability and efficacy. It also has two key advantages that make it an ideal assay
for flu vaccine potency. 1) It uses aptamers (nucleic acid ligands) to overcome the limitation of
antibodies. Because aptamers are developed in vitro, we can create a highly robust and rapid
process that yields new strain-specific aptamers in 4 weeks. Aptamers are more stable and
consistent than antibodies, and have a well-defined composition, and thus support
standardization and broad dissemination within the R&D community. 2) The device utilizes a
microfluidic multiplex electrochemical sensor design which enables rapid and accurate assays,
minimal hands-on time, and ease of manufacture. If successful, our product has the potential to
provide life-saving benefits by overcoming a critical risk in flu vaccine production.
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