UCI Professors Developing Method of Synthesizing Plastic Monoclonal Antibodies

By Anna Lynn Spitzer

12.02.05 – Red Tide, experienced first-hand this summer by Southern California beachgoers, is a neurotoxin-producing algae that is potentially fatal to humans when ingested. The condition requires that seafood be shipped to the Midwest where it undergoes a complicated extraction protocol to ensure safe consumption. Red Tide costs the U.S. an estimated $40 million to $100 million a year, according to ScienCentral News

 “If we could make a relatively inexpensive material that recognizes one of these toxins, we could develop a diagnostic to determine the toxicity level present in foods,” suggests Kenneth Shea, UCI professor of chemistry.

Lee and Shea
Professors Lee and Shea

Shea and Abraham Lee, professor of biomedical engineering, are working to develop such materials. The UCI pair, one of four winners of the Calit2 Nicholas Foundation Award for Cross-Disciplinary Research, is using their funds to develop a method of synthesizing plastic monoclonal antibodies that perform the same function as natural antibodies: recognition of foreign molecules.

In addition to determining toxin levels in seafood, there are plenty of applications for monoclonal antibodies including chemical sensors, biomedical diagnostics and compound purification. “The army is interested in sensors that are capable of detecting the presence of chemical warfare agents,” says Shea. “This requires recognizing the threatening molecule rapidly and efficiently using synthetic, robust materials instead of proteins or antibodies which are rather sensitive.”

Man-made Resilience

The goal is to develop antibodies and proteins out of synthetic polymers vigorous enough to function in organic solvents, at various temperatures and in an assortment of extreme environments – unlike natural antibodies, which are comfortable only in water with a neutral pH.

“We want to make materials – that we can produce in large quantities in a relatively straightforward way – that you can put on a hot plate and heat to 100 degrees without changing their functions,” explains Shea.

He has already developed a method for creating polyclonal antibodies, those that will recognize a wide range of molecules. Creating pure monoclonal antibodies that will recognize only one specific molecule is more difficult. One approach is to reduce the synthetic antibodies to the size of a large protein and then employ affinity chromatography, a technique used to separate proteins. By covering the surface of a column with the desired binding molecule and running a mixture of antibodies down the column, the antibodies with a high attraction for the specific molecule attach to the column while the rest flow through. The high-affinity antibodies can then be released by a change in the pH and collected.

A Complete Manufacturing Platform

It is not a simple task, however, to mass-produce uniform sub-micron size particles and put them through a separation technique. Enter Lee and his research on microfluidic devices. “The device allows you to control the formation of small particles that are more mimicking of a true antibody,” says Lee.

Using nanojet droplet synthesis, a microfluidic device can produce streams of perfectly uniform, sub-micron-size droplets, each containing a catalyst, a template molecule and monomers that will polymerize into the antibody. The droplets will flow down a microchannel where a UV light source will induce the polymerization reaction, turning the droplets into solid particles. The particles will then move through a series of switchbacks with walls coated with the target-binding molecule, stopping the particles with a high affinity. With this process, microfluidic devices will act as complete manufacturing platforms, simplifying the creation of synthetic monoclonal antibodies.

New Field Emerges

According to Shea and Lee, their cross-discipline collaboration looks to be long-term. “This is a major effort and this award has allowed us to begin all of the necessary steps in this complicated process, Shea says.” The process includes obtaining preliminary findings that lend credibility to their hypothesis in order to obtain funding from organizations such as the National Institutes of Health. “The Nicholas Foundation has provided the seed money,” remarks Shea, a sum of $80,000 that has allowed them to begin proving that it is possible to make uniform, sub-micron size particles.

The researchers see promise and possibility in the project. “We’re pretty excited to be opening up a new field,” states Lee. “Once we have our first successes, we anticipate many new research directions based on this technology as other scientists join in.”