Ultrasound based noninvasive real-time cell proliferation process monitoring

Abstract

The proliferation process's efficiency is related to the number of cells grown in culture and the maximum efficiency obtained at the stationary phase. Since the culture's growth speed is different for various cells and even for subgroups of the same cells, it is essential to monitor the process properly to obtain maximum efficiency. In this work, ultrasonic velocity measurement was performed noninvasively for wireless real-time monitoring of the suspension cell culture using a single integrated device to get maximum efficiency from the process by determining the phases. Using the advantage of the developed device's portability and wireless connectivity, the cells are monitored in the incubator without interfering with the actual process. Therefore, a real-time highly sampled growth curve is obtained, which was not possible to obtain with the currently used methods or the offline methods that are based on taking samples from the culture invasively. Filtering and curve fitting methods are also applied to the data to obtain a clean growth curve. The method developed as a result of this study ensures that the suspension cell culture was monitored most conveniently in the actual growth medium in real-time and noninvasively.

The Design of Low‐Cost Stand‐Alone Microcontroller‐Based Wireless Ultrasonic System for Process Monitoring and Analysis

“…In the system, both transmitter and receiver piezo have low power values. When the signals' mean powers are calculated in transmitter and receiver piezo, they are found to be approximately 0.18 and 0.04 mW respectively 17 . In addition to these low power values, the system does not work continuously.…”

“…In the developed system, pitch–catch principle is used 17 . The TOF value is calculated for these two signals' starting time.…”

“…In the developed system, pitch-catch principle is used. 17 The TOF value is calculated for these two signals' starting time. In the system, the start signal is generated the microcontroller, when the transmitted signal is generated.…”

“…Then, this signal is received by receiver piezo and the timer has been stopped and the stop signal is generated. The time difference of these is TOF 17 …”

“…The ultrasonic method is also used for process monitoring in the food industry. This method was used to monitor at malolactic fermentation process in red wines by Novoa‐Diaz et al 12 and Çelik et al, 13 at the lactic fermentation process in yogurt by Alouache et al, 14 for coagulation monitoring in cheesemaking by Budelli et al 15 Unlike these processes, Cha and Hitzmann used ultrasonic techniques to monitor Saccharomyces cerevisiae cultivation, 16 and Keskinoğlu and Aydin used this technique in cell proliferation monitoring in real‐time 17 . According to these studies, the ultrasonic technique is appropriate for process monitoring.…”