Affinity chromatography— controlled by light, not chemistry.

Why the elution step is the one worth changing

Classical affinity chromatography binds a target under gentle conditions and then changes the solution chemistry to let go of it — for Protein A, an acid step around pH 3.0 to 3.6. The chemistry that releases the product is also the chemistry the product has to survive, and for formats whose stability is marginal that trade is the constraint the whole process is designed around: collection into pre-loaded neutralisation buffer, small fractions, additives, sometimes a different ligand altogether. What changes with a light-controlled ligand is that the release is triggered physically rather than chemically, so the elution buffer becomes a choice about the next step instead of a compromise with this one.

The mechanism is a photoswitch built into the ligand scaffold. Under red light it holds the high-affinity conformation; a blue pulse isomerises it, the affinity collapses, and the target leaves in whatever buffer is flowing. Because the switch is reversible, the same capsule goes back to binding when the light changes again — demonstrated over more than 100 cycles with IgG, with performance declining across that range rather than staying flat.

What this does not solve

Four limits are worth stating plainly, because they decide whether the technology is relevant to a given process.

The light has to reach the whole bed. This is the physical constraint on any photo-controlled chromatography, and it dictates the format rather than the other way round: the switch only happens where the light arrives, so illumination has to be uniform across the adsorbent — which a deep packed column does not allow and a flat convective body does. It is the reason PureLight® is built on a monolith and not on a resin, and it is a real boundary on how such a device scales: by area rather than by bed depth.

The viral inactivation hold stays. In a licensed Fc process the longest acid exposure is not the elution but the low-pH hold that inactivates enveloped viruses, typically around pH 3.5 for 30 to 60 minutes. Light-controlled release takes the elution out of that acid budget; it does not take out the inactivation step, which has to be solved on its own terms where a product cannot take it.

Today the ligand is Protein A. Affinity capture of AAV runs on camelid VHH ligands and lentiviral capture usually on anion exchange, so for viral vectors the acid problem is real but the ligand does not exist yet on this platform. Extending beyond Protein A is what PureLight® is designed for, and it is a development programme rather than a catalogue.

What has been demonstrated is IgG. The formats this technology is aimed at — bispecifics, ADCs, Fc-fusions — are exactly the ones we have not yet run on it. That is what the Beta programme is for, and we would rather run the experiment with you than describe the result in advance.

How this differs from other light-controlled purification methods

Light-controlled protein purification is an active research field, and it is worth being precise about which part is being controlled. The published academic approaches put the photoswitch on the target protein: a genetically encoded photoswitchable side chain or a light-switchable binding domain is engineered into the molecule to be purified, which is then released by ultraviolet or blue light. For a recombinant research protein that is an elegant solution. For a therapeutic antibody it is not available at all — the product cannot carry a tag, and the molecule is what it is.

PureLight® puts the photoswitch in the ligand instead. The antibody is captured natively, with nothing added to it and nothing engineered into it, and the switch happens on the stationary phase. Two consequences follow: the method works on a molecule that was never designed for it, and the light that does the switching is visible rather than ultraviolet, which keeps the product out of the wavelength range where photodamage is a concern in the first place.

Whether light is the right answer at all depends on what is failing in your process. The full set of options for getting an antibody off a Protein A column without taking it to pH 3 — mild-elution ligands, amino-acid and arginine buffers, salt and calcium systems, detergents, alternative ligands, and simply shortening the acid contact — is compared in how to elute from Protein A without acid. Light-controlled release is one of nine routes there, and for most molecules it is not the first one to try.

Frequently asked questions

What is light-controlled affinity chromatography?

Affinity chromatography in which the ligand releases the target in response to light rather than to a change in pH or salt. In PureLight® the ligand carries a photoswitch: red light (630 nm) holds it in its binding conformation, a blue pulse (480 nm) isomerises it reversibly and the affinity collapses, so the product elutes in the buffer already flowing through the column.

How is it different from a mild-elution Protein A ligand?

Mild-elution ligands move the release to a higher pH — useful, and available today from several suppliers. They still release by changing the solution chemistry, so the elution buffer is still decided by the ligand. A light trigger separates the two questions: the release condition and the buffer your next step needs no longer have to be the same decision.

Does the light reach the ligand inside the matrix?

That is the first question any spectroscopist asks, and it is a device question rather than a chemistry one: the illumination is part of the Solaris® hardware rather than a lamp pointed at a column, and the geometry of matrix and light path is evaluated together with the chemistry. It is also one of the reasons the technology ships as a Beta programme rather than as a catalogue item.

Does the light damage the product?

The wavelengths are in the visible range — 630 and 480 nm — not the ultraviolet region associated with photodamage to proteins, and the pulse is short. Whether a specific molecule is indifferent to it is part of what an evaluation establishes.

When can I buy it?

Solaris® Protein A is in Beta evaluation by application, not commercial supply. If classical elution is the bottleneck in your process, that is the conversation to have — and if it is not, MonoCore™ Protein A runs the classical cycle on the same matrix today.