Real‐time monitoring of shake flask fermentation and off gas using triple disposable noninvasive optical sensors

Ge, Xudong; Rao, Govind

doi:10.1002/btpr.1528

Cited by 18 publications

(6 citation statements)

References 39 publications

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“…The method was applied to monitor pH changes caused by the growth and metabolism of a culture of the pathogen Staphylococcus aureus. Rao and co-workers integrated optical pH sensors (hydrogel-immobilized 6,8-dihydroxypyrene-1,3-disulfonic acid or Dowex-immobilized HPTS) and oxygen sensors in (micro)bioreactors for mammalian cell culture, 100,394 cultivation of E. coli 380,1169,1170 and effective clone selection. 1171 Good agreement was found between values obtained by optodes and electrodes, respectively.…”

Section: Sensing and Imaging Of Ph Values In Biotechnologymentioning

confidence: 99%

Optical Sensing and Imaging of pH Values: Spectroscopies, Materials, and Applications

2020

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This is the first comprehensive review on methods and materials for use in optical sensing of pH values and on applications of such sensors. The Review starts with an introduction that contains subsections on the definition of the pH value, a brief look back on optical methods for sensing of pH, on the effects of ionic strength on pH values and p K a values, on the selectivity, sensitivity, precision, dynamic ranges, and temperature dependence of such sensors. Commonly used optical sensing schemes are covered in a next main chapter, with subsections on methods based on absorptiometry, reflectometry, luminescence, refractive index, surface plasmon resonance, photonic crystals, turbidity, mechanical displacement, interferometry, and solvatochromism. This is followed by sections on absorptiometric and luminescent molecular probes for use pH in sensors. Further large sections cover polymeric hosts and supports, and methods for immobilization of indicator dyes. Further and more specific sections summarize the state of the art in materials with dual functionality (indicator and host), nanomaterials, sensors based on upconversion and 2-photon absorption, multiparameter sensors, imaging, and sensors for extreme pH values. A chapter on the many sensing formats has subsections on planar, fiber optic, evanescent wave, refractive index, surface plasmon resonance and holography based sensor designs, and on distributed sensing. Another section summarizes selected applications in areas, such as medicine, biology, oceanography, bioprocess monitoring, corrosion studies, on the use of pH sensors as transducers in biosensors and chemical sensors, and their integration into flow-injection analyzers, microfluidic devices, and lab-on-a-chip systems. An extra section is devoted to current challenges, with subsections on challenges of general nature and those of specific nature. A concluding section gives an outlook on potential future trends and perspectives.

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Section: Sensing and Imaging Of Ph Values In Biotechnologymentioning

confidence: 99%

Optical Sensing and Imaging of pH Values: Spectroscopies, Materials, and Applications

2020

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“…To our knowledge, this is the first study to report that the CO 2 concentration increases (~85.0 mg/L) during shake-flask culture using a culture plug-capped Erlenmeyer flask, compared with the initial culture condition (~4.0 mg/L). A previous study has reported the monitoring of dissolved CO 2 in shake-flask culture (Ge and Rao 2012 ). However, this study focused on the development of a sensor for dissolved CO 2 and O 2 , and the pH in the flask was different from that at standard conditions of shake-flask culture (a milk filter and 2 L flask filled with 50 mL of medium).…”

Section: Discussionmentioning

confidence: 99%

Development of a circulation direct sampling and monitoring system for O2 and CO2 concentrations in the gas–liquid phases of shake-flask systems during microbial cell culture

Takahashi

Sawada²,

Aoyagi

2017

AMB Expr

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Monitoring the environmental factors during shake-flask culture of microorganisms can help to optimise the initial steps of bioprocess development. Herein, we developed a circulation direct monitoring and sampling system (CDMSS) that can monitor the behaviour of CO2 and O2 in the gas–liquid phases and obtain a sample without interrupting the shaking of the culture in Erlenmeyer flasks capped with breathable culture plugs. Shake-flask culturing of Escherichia coli using this set-up indicated that a high concentration of CO2 accumulated not only in the headspace (maximum ~100 mg/L) but also in the culture broth (maximum ~85 mg/L) during the logarithmic phase (4.5–9.0 h). By packing a CO2 absorbent in the gas circulation unit of CDMSS, a specialised shake-flask culture was developed to remove CO2 from the headspace. It was posited that removing CO2 from the headspace would suppress increases in the dissolved CO2 concentration in the culture broth (maximum ~15 mg/L). Furthermore, the logarithmic growth phase (4.5–12.0 h) was extended, the U.O.D.580 and pH value increased, and acetic acid concentration was reduced, compared with the control. To our knowledge, this is the first report of a method aimed at improving the growth of E. coli cells without changing the composition of the medium, temperature, and shaking conditions.

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“…Based on similar principles, a fiber‐optic sensor has been made for on‐line monitoring of dissolved CO 2 using pH sensitive dye entrapped in gas permeable membrane . In another design, a patch with a responsive layer of pH sensitive fluorophore can be affixed to the inside wall of the flask to measure CO 2 concentration in both gas and liquid phases .…”

Section: Sensors Commonly Used In Bioprocessmentioning

confidence: 99%

Advances in process monitoring tools for cell culture bioprocesses

Zhao

Zhou

et al. 2015

Engineering in Life Sciences

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Practical applicationThis review summarizes recent progress and current status of bioprocess monitoring. There has been an increasing emphasis on the applications of process analytical tools in bioprocessing for biologics manufacturing. The integration of in-line, on-line and at-line sensors and the real-time characterization of the physiological state of cells will lead to robust processes and enhanced product quality. AbstractThe productivity of cell culture manufacturing for biologics has increased momentously in the past decades. Increasingly, the process research efforts are devoted into improving product quality and consistency. Consistent process performance and successful implementation of quality by design (QbD) practice requires well-utilized process analytical technology (PAT). This review summarizes recent progress and current status of bioprocess monitoring. Many sensors for bioprocess monitoring have been available for decades while new ones, especially spectrometric sensors, are making their way into cell culture bioprocesses. On-line sampling devices have grown mature in the past decade thus making many instruments traditionally used for off-line analysis available for at-line use. With a general trend of using better defined medium for cell cultivation and increasing emphasis of process analytical tools, the spectrometric methods are also making headway in cell culture process monitoring. The integration of those sensing technologies will be important to advance the real-time monitoring of the state of cellular physiology for the control for process consistency and product quality.

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Real‐time monitoring of shake flask fermentation and off gas using triple disposable noninvasive optical sensors

Cited by 18 publications

References 39 publications

Optical Sensing and Imaging of pH Values: Spectroscopies, Materials, and Applications

Optical Sensing and Imaging of pH Values: Spectroscopies, Materials, and Applications

Development of a circulation direct sampling and monitoring system for O2 and CO2 concentrations in the gas–liquid phases of shake-flask systems during microbial cell culture

Advances in process monitoring tools for cell culture bioprocesses

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