August 1, 2015 (Vol. 35, No. 14)

New Single-Use, Column-Free Chromatography Method Raises Efficiency, Lowers Costs

ChromaTan’s continuous and single-use chromatography system breaks the bottlenecks inherent in traditional column chromatography, enabling cost-effective, steady-state operation. This system, Countercurrent Tangential Chromatography (CTC) is designed to accommodate recent advances in bioprocessing and cell culture technology.

“Improvements in cell culture and bioreactor design during the past 15 years have increased antibody titers from less than 0.5 g/L to more than 10 g/L, and downstream processing hasn’t caught up,” says ChromaTan CEO Oleg Shinkazh. “Column chromatography is reaching its limits in throughput and capacity.”

Column chromatography poses another challenge: expense. Costs begin to mount with the purchase and installation of expensive equipment, and keep rising every time pricey resins are ordered. Protein A resins for antibody capture, for example, cost $10,000–15,000/L, Shinkazh tells GEN. “With large-scale column sizes approaching 1,000 L, that’s $10–15 million,” he adds. Cleaning and validation costs further escalate expenses. CTC overcomes many of these challenges.

Boris Napadensky, the vice president of engineering at ChromaTan, installs disposable pump heads on ChromaTan’s pilot CTC system.

How it Works

“The CTC process uses the resin in the form of a slurry that flows through a series of static mixers and hollow-fiber membrane modules,” Shinkazh explains. “The microporous hollow-fiber membranes retain the large resin particles while letting all dissolved species, including proteins and buffer components, pass through the membrane and into the permeate.”

The buffers used in the binding, washing, elution, stripping, and equilibration steps flow countercurrent to the resin slurry in a multistage configuration, enabling high-resolution separations while reducing the amount of buffer needed for protein purification. Because the pressure decrease in CTC is low—less than 20 psi—a disposable flow path can be used.

“Ours is a truly continuous operation,” Shinkazh emphasizes. “In contrast, multicolumn systems are only semicontinuous. Their effluent comes out in pulses.” With ChromaTan’s system, Shinkazh asserts, there are no peaks. “Instead, our system outputs the product at a constant concentration and flow rate, which is a large advantage for post-processing.”

Because the resin is suspended in a continuously circulating slurry, there are no columns to pack, clean, or validate, and little resin to store.

“Unlike prepacked columns, users have the option to recover and reuse resin between batches while using different single-use flow paths. CTC reduces the resin volume by up to 90%,” Shinkazh tells GEN. The gamma-irradiated components in this modular system can enable users to reduce up-front costs. For example, they can run “pay as you make it” campaigns that use the same hardware for multiple products.


ChromaTan’s in-house tests of its CTC system indicate three- to six-fold improvements in productivity compared to column chromatography. The company, says Shinkazh, is pushing that number even higher.

“We’re in the middle of a ChromaTan blitz,” Shinkazh insists. “[We have] alpha trials underway at multiple leading biotech companies.” These companies are assessing ChromaTan’s systems in their own labs, and they are providing feedback to optimize the final product.

While that feedback is protected by nondisclosure agreements, Shinkazh does indicate that output is increasing. “Initial output was 55 g of product per liter of resin per hour (g/L/hour),” he specifies. “We’re currently seeing more than 70 g/L/hour.”

ChromaTan Evolution

While working in R&D at Millipore and in technical support for a Pall distributor, Shinkazh perceived a connection between costs and purification processes: “I saw many companies pouring money down the drain because of inefficient batch column systems.” For example, the low quantity of clinical manufacturing batches within companies means that expensive Protein A media typically is discarded although only 5–10% of its capacity is consumed. He says continuous chromatography could increase chromatographic efficiency by a factor of 10.

Shinkazh founded ChromaTan in 2009 at the Mass Challenge accelerator in Boston and won grants from the National Institutes of Health for Phase I and Phase II development, as well as financing from Ben Franklin Technology Partners of Central Pennsylvania. ChromaTan later moved to the Innovation Park incubator in State College, PA, attracted by its proximity to Penn State.

Since then, ChromaTan has raised approximately $2.9 million in equity and nondilutive grants. It has executed research partnerships with Fujifilm Diosynth, a contract manufacturer; Regeneron Pharma, an antibody developer; and Penn State University, which has helped with laboratory space, initial research, and fundraising.

Key board members include Andrew Zydney, Ph.D., a leading bioseparations researcher and head of Penn State’s chemical engineering department, and Paul H. Silvis, an entrepreneur who founded the chromatography supply company Restek and grew it to a $60 million company.

Now ChromaTan has entered into an agreement with ASI (an international provider of single use solutions, recently acquired by Thermo Fisher) to manufacture the single-use flow path of the CTC system. “ASI is responsible for manufacturing and quality control,” Shinkazh makes clear.

ChromaTan plans to develop its marketing efforts in-house. “We’re currently focused on the technical side, optimizing design,” Shinkazh points out. “Then we will look for additional capital.”

Shinkazh is talking with organizations about their interest in licensing the technology or acquiring the company. He welcomes “inquiries from interested parties with dedicated technology-evaluation programs to engage in co-developing CTC or developing the platform globally.” The system’s commercial launch is slated for 2016.


Location: 200 Innovation Blvd, Ste 260B, State College, PA 16803

Phone: (617) 529-0784


Principal: Oleg Shinkazh, CEO

Number of Employees: 5

Focus: ChromaTan has developed, Countercurrent Tangential, Chromatography (CTC)—a new column-free and single-use, process that can provide a cost-saving alternative to conventional column chromatography.

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