Numerous therapeutic or biopharmaceutical protein products enhance our daily lives. Unfortunately, many of these biopharmaceutical products are cost-prohibitive to a substantial portion of the country’s population. High production costs associated with conventional manufacturing techniques are the principal driving factor for high drug costs. Biopharmaceuticals are produced in commercial bioreactors by genetically-modified organisms that are suspended in a growth medium that contains nutrients such as glucose and vitamins. In times past, large stainless steel reactors were used to produce biopharmaceuticals such as penicillin. However, as the biopharmaceutical market continues to expand, there is a strong momentum to reduce manufacturing costs by replacing stainless steel bioreactors with smaller single-use bioreactors (SUBs) fabricated from polymeric materials like polyethylene. SUBs require a much lower capital investment than stainless steel bioreactors, and do not need to be repeatedly sterilized, because they are used only once. One of the industry leaders in the manufacture of SUBs is located in Logan, Utah: Hyclone (now a division of ThermFisher Inc.). Unfortunately, the development of sensors has not kept pace with the development of SUBs, because most of the currently-available sensors were developed for use in stainless steel bioreactors. Sensors are needed to maintain bioprocess conditions such as the glucose concentration within the bioreactor in order to optimize the quality of the end-products. Sensors used to monitor bioprocess conditions within stainless steel bioreactors do not translate well to SUBs. According to a 2014 report of The Economist, development of single-use sensors designed for SUBs could reduce biopharmaceutical manufacturing costs by 30%.
In the Department of Chemical Engineering we are addressing this commercial need by developing microfabricated sensor arrays for bioreactors that use stimuli-responsive hydrogels as the recognition elements for determining the concentration of target analytes in the growth medium within the bioreactor. This work is a collaboration between Professor Magda of the Department of Chemical Engineering, and Applied Biosensors, Inc. (http://appliedbiosensors.com/), a local start-up company formed by Dr. Prashant Tathireddy, a graduate of our chemical engineering department (PhD 1995). A stimuli-responsive hydrogel is a cross-linked polymer network that reversibly absorbs water and changes its degree of swelling in response to the change in concentration of a target analyte of interest such as glucose or salt. Stimuli-responsive hydrogels that selectively respond to pH, glucose concentration, and salt concentration are being synthesized in the laboratory of Professor Magda of the Department of Chemical Engineering. The swelling response of these stimuli-responsive hydrogels can be transduced into a measurable electrical signal using a microfabricated piezoresistive pressure sensor or a magnetometer. The single-use bioreactor sensors so obtained has advantages over traditional stainless steel bioreactor sensors such as lower cost, longer shelf-life, and greater stability to sterilization protocols such as gamma-sterilization. This research is being funded by the National Science Foundation Small Business Innovation Research program.