A rapid, sensitive, and quantitative high plex biomarker digital detection platform enabled by Hypercoding

Bathina, M.; Blum, A. P.; Brodin, J.; DeBuono, N.; Fu, Y.; Lu, B.; Naticchia, M. R.; Ortiz, D.; Richards, A.; Rozieres, C. d.; Schowalter, R.; Shultzaberger, S.; Snow, S.; Tanner, S.; Trejo, C. L.; Ward, S.; LeCoultre, R.; Read, K.; Sathe, S.; Schlegel, C.; Schlegel, I.; Shaner, S.; Tsay, J.; Weir, J.; Wong, K. M.; Abi-Samra, K.; Alldredge, J.; Anderson, P.; Bailey, J.; Bollig, C.; Bonnardel, J.; Bru, A.; Chan, A. C. S.; Chang, T.; DeBerg, L.; Doorn, J. v.; Driscoll, P.; Duarte, T.; Esparza, A.; Frerichs, D.; Gautherot, A.; Held, L.; Hendricks, G.; Holst, G.; Iwamoto, K.; Jimenez, H.; Khandan,

doi:10.64898/2026.03.23.711448

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bioRxiv · 10.64898/2026.03.23.711448

A rapid, sensitive, and quantitative high plex biomarker digital detection platform enabled by Hypercoding

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Abstract

Low-cost, multiplexed, and automated assays are needed to make omic technologies more broadly accessible in clinical, research, and commercial settings. We present Hypercoding, a scalable technology for detection and quantitation of multi-omic targets. Drawing from data reliability methods in the telecommunications field, Hypercoding uses fluorescent signals from hybridization with an error-correcting code to enable detection of high-plexity targets from biological samples, such as human DNA. In the presence of the target, a linear DNA construct is circularized, immobilized, and amplified to enable single-molecule detection of a target via rapid readout cycles within a 96-well plate. We demonstrate capability for >10,000 code plexity and accurate (98.7%) genotyping of 209 pharmacogenomic variants. Furthermore, we show computation of copy number variation with whole chromosome and sub-gene resolution, as well as quantitation of target abundance down to 10 fM sensitivity with a dynamic range of up to 10 logs.

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Bathina, M., Blum, A. P., Brodin, J., DeBuono, N., Fu, Y., Lu, B., Naticchia, M. R., Ortiz, D., Richards, A., Rozieres, C. d., Schowalter, R., Shultzaberger, S., Snow, S., Tanner, S., Trejo, C. L., Ward, S., LeCoultre, R., Read, K., Sathe, S., Schlegel, C., Schlegel, I., Shaner, S., Tsay, J., Weir, J., Wong, K. M., Abi-Samra, K., Alldredge, J., Anderson, P., Bailey, J., Bollig, C., Bonnardel, J., Bru, A., Chan, A. C. S., Chang, T., DeBerg, L., Doorn, J. v., Driscoll, P., Duarte, T., Esparza, A., Frerichs, D., Gautherot, A., Held, L., Hendricks, G., Holst, G., Iwamoto, K., Jimenez, H., Khandan,. 2026-03-25. A rapid, sensitive, and quantitative high plex biomarker digital detection platform enabled by Hypercoding. https://doi.org/10.64898/2026.03.23.711448

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