An apparatus that includes highly miniaturized thin-film electrochemical sensor array has been demonstrated as a prototype of instruments for simultaneous detection of multiple substances of interest (analytes) and measurement of acidity or alkalinity in bioprocess streams. Measurements of pH and of concentrations of nutrients and wastes in cell-culture media, made by use of these instruments, are to be used as feedback for optimizing the growth of cells or the production of desired substances by the cultured cells. The apparatus is designed to utilize samples of minimal volume so as to minimize any perturbation of monitored processes.
The apparatus can function in a potentiometric mode (for measuring pH), an amperometric mode (detecting analytes via oxidation/reduction reactions), or both. The sensor array is planar and includes multiple thin-film microelectrodes covered with hydrous iridium oxide. The oxide layer on each electrode serves as both a protective and electrochemical transducing layer. In its transducing role, the oxide provides electrical conductivity for amperometric measurement or pH response for potentiometric measurement. The oxide on an electrode can also serve as a matrix for one or more enzymes that render the electrode sensitive to a specific analyte. In addition to transducing electrodes, the array includes electrodes for potential control. The array can be fabricated by techniques familiar to the microelectronics industry.
The sensor array is housed in a thin-film liquid-flow cell that has a total volume of about 100 mL. The flow cell is connected to a computer-controlled subsystem that periodically draws samples from the bioprocess stream to be monitored. Before entering the cell, each 100-mL sample is subjected to tangential-flow filtration to remove particles. In the present version of the apparatus, the electrodes are operated under control by a potentiostat and are used to simultaneously measure the pH and the concentration of glucose. It is anticipated that development of procedures for trapping more enzymes into hydrous iridium oxide (and possibly into other electroactive metal oxides) and of means for imparting long-term stability to the transducer layers should make it possible to monitor concentrations of products of many enzyme reactions — for example, such key bioprocess analytes as amino acids, vitamins, lactose, and acetate.
This work was done by R. David Rauh of EIC Laboratories, Inc., for Johnson Space Center. For more information, download the Technical Support Package (free white paper) at www.medicaldesignbriefs.com .
In accordance with Public Law 96-517, the contractor has elected to retain title to this invention. Inquiries concerning rights for its commercial use should be addressed to:
Jeffrey L. Bursell, Controller/Contract Administrator
EIC Laboratories, Inc.
111 Downey Street
Norwood, MA 02062
Phone No.: (781) 769-9450
Refer to MSC-23578-1, volume and number of this NASA Tech Briefs issue, and the page number.
This Brief includes a Technical Support Package (TSP).
Electrochemical Detection of Multiple Bioprocess Analytes
(reference MSC-23578-1) is currently available for download from the TSP library.
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Overview
The document outlines an innovative approach to the electrochemical detection of multiple bioprocess analytes, primarily focusing on the development of biosensors that can monitor critical components in bioprocessing with minimal sample volume. The technology is particularly relevant for the pharmaceutical industry, where maintaining precise control over nutrient and metabolic waste levels is essential for optimizing the growth of bacteria, cells, or cell by-products.
At the core of this innovation is a planar array of thin-film electrodes housed in a compact liquid flow cell with a volume of approximately 100 microliters. This setup allows for the simultaneous detection of analytes such as glucose and pH, utilizing a potentiostat to control the electrodes. The electrodes are designed to minimize sample loss, enabling more frequent sampling and tighter control of medium composition. The biosensors leverage a metal oxide matrix, specifically hydrous iridium oxide, which serves dual functions: acting as a pH sensor and facilitating electrochemical reactions.
The document highlights the unique features of the technology, including its ability to trap enzymes within the electrochemical matrix, which enhances the stability and performance of the sensors. The sensors have shown excellent stability for pH measurements, although glucose sensors have exhibited some instability in oxygen-containing media. The innovation aims to address the limitations of prior art, which often faced challenges related to low stability and enzyme loading.
Potential commercial applications of this technology extend beyond bioprocessing to include clinical monitoring of blood constituents and urinalysis. The document emphasizes the adaptability of the sensors to a wide variety of enzymes and analytes, suggesting that future developments could enable the measurement of various bioprocess analytes, such as amino acids, vitamins, lactose, and acetate.
Overall, the document presents a significant advancement in biosensor technology, promising to enhance the efficiency and effectiveness of bioprocess monitoring while reducing the volume of samples required. This innovation not only addresses existing challenges in bioprocessing but also opens new avenues for research and application in various fields, including healthcare and pharmaceuticals.
