Solvent Correction: One More Extra Step To Accurate Data
November 29, 2016
Reduce or Eliminate Bulk Responses from Solvent Effects in Your Measurements
Getting the data needed to characterize drug candidates can be fraught with hurdles. Surface plasmon resonance (SPR) and BioLayer Interferometry (BLI) tools provide affinity and kinetic analysis, but they require solvent correction with carefully prepared reference samples to subtract large bulk responses. Organic solvents such as DMSO have bulk responses orders of magnitude larger than the response of a potential drug candidate and require reference samples prior to or in parallel with the actual experiment. These reference samples can consume additional sensor cells and precious biomaterial, and any difference between the reference run and experimental run adds inaccuracy to the data. Isn’t getting accurate data hard enough already?

You Can’t Hear a Whisper in a Thunderstorm
On SPR and BLI tools, organic solvents cause a large optical response relative to the targeted binding interaction. Essentially, you’re trying to hear a whisper with a storm raging around you. SPR and BLI measurements require solvent correction to subtract background noise and provide accurate results. There is a new technique available that doesn’t require solvent correction called Field-Effect Biosensing (FEB). Unlike SPR and BLI which are optical methods, FEB systems are electronic and charged-based, leveraging advances in solid state electronics to put more computing power into your pocket than was used by the entirety of the NASA to put men on the moon. FEB measures the electrical current across an atomically-thin conductive sensor surface with immobilized capture molecules. The electrical current changes in real-time as binding occurs at the sensor surface, enabling accurate affinity and kinetic data. On a charge-based FEB system, organic solvents have minimal effect because they are net-neutral molecules that do not significantly affect the biosensor. Now you’re listening for the whisper in a quiet room.

Avoid Lab Fires with DMSO-resistant FEB technology
The standard way to find a needle in haystack is to set it on fire and then use a magnet, but your facilities crew and PI won’t appreciate a fire in the lab. It’s probably safer to utilize an FEB assay.

For those who are more Jerry Maguire-minded and need to be shown the data, here are four standard curves from an FEB sensor (Agile Biosensor Chip from Nanomedical Diagnostics) functionalized with TNF-α, a cell signaling protein implicated in Alzheimer’s disease and cancer. The target analyte is SPD304, a small molecule inhibitor of TNF-α. Each colored set of data points represents a concentration series of SPD304 in a buffer containing 0%, 1%, 3%, or 10% DMSO. The overlapping fit curves with identical dissociation constants (deviations are not statistically significant) demonstrate that sensor response is unaffected by DMSO concentration and does not require additional multi-step referencing protocols such as solvent correction.


Related Literature

More about solvent correction, SPR, BLI, and FEB: