Applied Biosensors

Applied Biosensors' device, AB Sense

Enabling Growth in the Bioprocessing Industry

A growing percentage of pharmaceutical drugs on the market today are biologics, medicines grown from living cells in bioreactors. A bioreactor is, in essence, an enclosed brewing system that supports a biologically active environment where microorganisms make complex molecules, including biologic drugs.

For much of the history of modern drug making such biologics have been grown in giant, sophisticated steel-based bioreactors that cost millions of dollars and nearly the same amount to maintain and operate. Between each batch of drugs considerable cleaning, sterilization, and validation steps must be meticulously performed. Such downtime has become a major bottleneck in the biopharmaceutical industry. The time lost between each batch significantly lowers the number of batches of drugs these multi-use bioreactors can produce. The downtime and cost is multiplied when cross contamination takes place from failure to properly sterilize, a problem that is estimated to occur around five percent of the time.

Seungoh Ko, Vishal Bhola, Rich Barra, Prashant Tathireddy, Jules Magda, Seung Hei Cho, and Tram Nguyen

Eliminating the cost, time, and risk of contamination associated with these cumbersome processes has been the driving force behind the rapid growth of single-use technologies in this industry over the last 10 years. Unlike their multi-use competitors, single-use bioreactors are often small, mobile, inexpensive, and pre-sterilized. They are significantly reducing overall expenses and speeding up the time it takes drugs to get to market.

Lack of Disposable Sensors

The adoption of single-use technologies has, however, encountered its own significant bottleneck in recent years: the lack of disposable sensors. Bioreactor sensors are what give biomanufacturers the ability to measure what is taking place in a bioreactor. Analytes such as pH, glucose, and lactic acid are monitored through these sensors in an effort to maintain consistent process performance. “The relative lack of single-use sensors in the market is one of the factors limiting the growth and adoption rates of single-use technologies,” explains Prashant Tathireddy, Ph.D., research associate professor of electrical and computer engineering at the U, and founder and CTO of U-spinout Applied Biosensors. “Customers who purchase single-use bioreactors are having to sterilize and reuse available sensor probes, and perform off-line sampling for most analytes, which defeats the purpose of contact-free, sterile, single-use technologies.”

Current classical methods for measuring most analytes involve removing samples from the bioreactor and then performing measurements using expensive laboratory equipment. “This approach,” Tathireddy explains, “suffers from several drawbacks: it only provides intermittent values and it increases the risk of bioreactor contamination.”

Applied Biosensors’ Single-Use Sensor

Tathireddy is confident that the sensor Applied Biosensors developed, AB Sense, will eliminate this major bottleneck. This inexpensive, single-use sensor can monitor multiple new analytes simultaneously and in real-time, something its competitors cannot achieve. It is able to do this because it is compartmentalized like a pie with each piece containing a hydrogel made sensitive to a specific analyte. This design eliminates the need for the biomanufacturer to have multiple sensors and perform off-line measurements.

A single-use bioreactor

AB Sense is able to monitor multiple analytes largely because of the special hydrogels it uses. Developed by Jules Magda, Ph.D., professor of chemical engineering at the U, these hydrogels are made up of smart polymers that respond in a dramatic way to slight changes in their environment. “For example, if the concentration of glucose increases in the environment the polymer network swells,” Magda explains. “When the concentration goes down, it de-swells.” The sensor detects these often minute changes by monitoring the magnetic field produced by magnetic particles embedded in the hydrogels. When the polymers change in volume, the magnetic field changes as well, which directly correlates to the concentration of the chemical being measured.

Measuring changes in the magnetic field enables continuous monitoring. With the long-lasting biocompatible hydrogels on the inside of the bioreactor, the electronics are attached as long as needed to the outside and are thus never in contact with the medium. The electronics also transmit data wirelessly and continuously to process control systems, completely eliminating the need to take samples intermittently. “This benefit,” explains Rich Barra, Applied Biosensors’ CEO, “is very important to the industry because the production of biologics depends entirely on the process in which they are made.” Drug consistency, quality, and purity must remain highly stable from batch to batch and the only way this can be achieved is through extensive control of the environment inside the bioreactor. Even the slightest of adjustments in the manufacturing process can result in dramatic, costly, and unacceptable changes to the drug. Continuous and accurate monitoring provided by AB Sense will significantly reduce the risk of such setbacks from occurring.

Moving to Market

Barra anticipates having a commercially-ready product available on the market in 18 months. This, he explains, can’t come soon enough for the industry: “We have talked to 15 big companies in this space and from these conversations we know that there is considerable demand for quality disposable probes and sensors like ours. They are the final item needed for having a fully disposable operation.”

Return to Report Home Next Article: iCORDS: Mitigating the Risk of Oil Exploration