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SENSORS FOR DETECTION OF PROTEINS AND VIRUS PARTICLES IN COMPLEX STREAMS OF BIO-MANUFACTURING PROCESSES

IP.com Disclosure Number: IPCOM000245177D
Publication Date: 2016-Feb-17

Publishing Venue

The IP.com Prior Art Database

Abstract

A technique for selective real-time sensing of protein aggregation and virus particles in a complex stream such as that of a bio-manufacturing process (for example, a biopharmaceutical manufacturing) is disclosed. According to one embodiment the sensor is an electrical resonator for detecting protein aggregates. According to another embodiment, the sensor is a radiofrequency resonator for detecting viral particles.

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SENSORS FOR DETECTION OF PROTEINS AND VIRUS PARTICLES IN COMPLEX STREAMS OF BIO-MANUFACTURING PROCESSES

BACKGROUND

 

The present disclosure relates generally to biopharmaceutical manufacturing and more particularly to a technique for real-time sensing of protein aggregation and virus particles in a complex stream such as that of a biopharmaceutical manufacturing is disclosed.

Generally, for producing high quality and safe biopharmaceuticals monitoring manufacturing parameters is critical. Various sensors are available for continuous monitoring of temperature, conductivity, pressure, pH, glucose, dissolved oxygen, and cell mass. However, all parameters that are critical for high quality production cannot be monitored using sensors generally available in the art.

Some parameters such as protein aggregation and virus concentrations are measured in real-time using laboratory analytical instruments because of unavailability of sensors for these parameters. These methods for real time in-line detection of protein aggregation present multiple challenges. Key challenges include inability to perform accurate measurements over diverse environmental conditions and in presence of numerous interferences and the need to use auxiliary reagents to visualize aggregation.

Further, virus sensing is also critical. For example, detection of minute virus of mice (MVM) is of primary importance in biopharmaceutical manufacturing. MVM adventitiously infects Chinese Hamster Ovary (CHO) cell lines that are commonly used for production of monoclonal antibodies (mAb). Therefore, detection of viral infection in the upstream process at multiple points in the manufacturing process is critical. These check points include testing of culture media components, cell-lines, seed-train, and bioreactor where virus concentrations are typically in the range of 103 – 105/mL. Therefore, lack of virus sensors is one of the most important deficiencies in bio-manufacturing.

It would be desirable to have a technique for sensing protein aggregation and virus concentration in complex streams such as those of biopharmaceutical manufacturing process.

BRIEF DESCRIPTION OF DRAWINGS

Figure 1 depicts principle of measurements of protein aggregation in the presence of variable background: (A) Sensing region where the resistance and capacitance of the sensing region change as a function of sample composition; and (B) Protein aggregates predictably affect the electric field of the sensing region..

Figure 2 depicts operation principle of passive RFID sensors which includes measuring impedance spectrum (real part Zre(f) and imaginary part Zim(f) of impedance) and calculated parameters from the measured Ž(f) spectra that included the frequency position Fp and magnitude Zp of Zre(f) and the resonant F1 and antiresonant F2 frequencies, their impedance magnitudes Z1 and Z2 of Zim(f), and zero-reactance frequency FZ of Zim(f).

Figure 3 depicts a sampling-centrifugation-sensing process for quantitation o...