Real-time monitoring of cellular biomass: Methods and applications

Kell, Douglas B.; Markx, Gerard H.; Davey, Christopher L.; Todd, Robert W.

doi:10.1016/0165-9936(90)87042-k

Cited by 126 publications

(58 citation statements)

References 16 publications

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“…A body of literature exists that has both measured and modelled the electrical changes in cells and tissue both in vivo and in vitro, as well as provided correlations between electrical properties and cell types; this work has been summarized previously [6][7][8][9][10][11] . From an electrical perspective, a cell can be represented as an ion-rich conductive centre (cytoplasm) embedded in an ion-rich conductive medium (extracellular fluid), separated by a relatively non-conductive barrier (cell membrane).…”

mentioning

confidence: 99%

“…For example, in vitro impedance measurements have been shown to detect cell proliferation and cell-drug interaction 12 , quantify biomass in suspensions 11,13 and create two-dimensional images of cell migration 14 . Much of this work utilizes the electrical 'signature' of the cell membrane: a well-functioning cell membrane is relatively impermeable and thus behaves like a capacitor in the presence of electric current [9][10][11]13,15 . Cell damage or death results in a loss of membrane structure and integrity, allowing ions and current to pass through the membrane.…”

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Impedance sensing device enables early detection of pressure ulcers in vivo

et al. 2015

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When pressure is applied to a localized area of the body for an extended time, the resulting loss of blood flow and subsequent reperfusion to the tissue causes cell death and a pressure ulcer develops. Preventing pressure ulcers is challenging because the combination of pressure and time that results in tissue damage varies widely between patients, and the underlying damage is often severe by the time a surface wound becomes visible. Currently, no method exists to detect early tissue damage and enable intervention. Here we demonstrate a flexible, electronic device that non-invasively maps pressure-induced tissue damage, even when such damage cannot be visually observed. Using impedance spectroscopy across flexible electrode arrays in vivo on a rat model, we find that impedance is robustly correlated with tissue health across multiple animals and wound types. Our results demonstrate the feasibility of an automated, non-invasive 'smart bandage' for early detection of pressure ulcers.

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Impedance sensing device enables early detection of pressure ulcers in vivo

et al. 2015

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“…There are several disadvantages associated with optical biomass measurement (see e.g. Harris and Kell, 1985;Kell et al, 1990;Sonnleitner et al, 1992, Junker et al 1994, the most important of which are that optical density is linear with biomass only over a very narrow range of low biomass concentrations, such that for most organisms the O.D. fails to be linear at concentrations well below those at which they would be of industrial interest.…”

Section: Introductionmentioning

confidence: 99%

“…Harris et al, 1987;Kell et al, 1987Kell et al, , 1990Davey, 1993a,b)). Continuous cultures in which the biomass is set by the Biomass Monitor have been called 'permittistats' because the biomass is kept at a constant level by a feedback mechanism based on the dielectric permittivity of the suspension, and this approach has previously been used with great success for controlling anaerobic yeast cultures (Markx et al, 1991a).…”

Section: Introductionmentioning

confidence: 99%

“…A third problem with turbidity measurements is that it is not only biomass that is measured, since necromass, particulate solids, and gas bubbles will all contribute to the optical density to some extent. For these reasons, novel methods for the on-line and realtime measurement of the biomass content of industrial fermentations have long been an area of interest (Harris and Kell, 1985;Clarke et al, 1986;Kell et al, 1990;Sonnleitner et al, 1992). …”

Section: Introductionmentioning

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Oscillatory, stochastic and chaotic growth rate fluctuations in permittistatically controlled yeast cultures

Davey

Woodward

et al. 1996

Biosystems

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We describe a continuous culture syste,m related to the turbidostat, but using a feedback system based on biomass estimation from the dielectric permittivity of the cell suspension rather than its optical density. It is shown that this system provides an excellent method of maintaining a constant biomass level within a fermentor. The computercontrolled system was able to effect the essentially continuous registration of growth rate by monitoring the rate of medium addition via the time-dependent activity of the pump. At some biomass setpoints for aerobically grown cultures of baker's yeast substantial time-dependent fluctuations in the growth rate of the culture were thereby observed. At some biomass setpoints, however, or under anaerobic conditions, or when using a nonCrabtree yeast, the growth rate was constant, indicating that the fluctuations were inherent to the biological system and not simply a property of the fermentor and control system. A variety of time series analyses (Fourier transformations, Hurst and Lyapunov exponents, the determination of embedding dimension, and non-linear time series predictions based on the methodology of Sugihara and May) were used to demonstrate, for the first time, that as well as stochastic and periodic components these fluctuations exhibited deterministic chaos. 'Trivial predictors' were unable to give accurate predictions of the growth rate in these cultures. The growth rate fluctuations were studied further by means of offline measummenta of changes in percentage viability, bud count, and in the external ethanol and glucose concentrations; these data and other evidence suggested that the growth rate fluctuations were closely linked to the primary respirofermentative metabolism of this organism. The identification of chaotic growth rates in cell cultures suggests that there may be novel methods for controlling the growth of such cultures.

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Quantification of microbial productivity via multi-angle light scattering and supervised learning

Jones

Young

Taylor

et al. 1998

Biotechnol. Bioeng.

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This article describes the use of chemometric methods for prediction of biological parameters of cell suspensions on the basis of their light scattering profiles. Laser light is directed into a vial or flow cell containing media from the suspension. The intensity of the scattered light is recorded at 18 angles. Supervised learning methods are then used to calibrate a model relating the parameter of interest to the intensity values. Using such models opens up the possibility of estimating the biological properties of fermentor broths extremely rapidly (typically every 4 sec), and, using the flow cell, without user interaction. Our work has demonstrated the usefulness of this approach for estimation of yeast cell counts over a wide range of values (105–109 cells mL−1), although it was less successful in predicting cell viability in such suspensions. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 59:131–143, 1998.

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Real-time monitoring of cellular biomass: Methods and applications

Cited by 126 publications

References 16 publications

Impedance sensing device enables early detection of pressure ulcers in vivo

Impedance sensing device enables early detection of pressure ulcers in vivo

Oscillatory, stochastic and chaotic growth rate fluctuations in permittistatically controlled yeast cultures

Quantification of microbial productivity via multi-angle light scattering and supervised learning

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