Fluorescent Sensing and Process Analytical Applications

Dickens, Jason E.

doi:10.1002/9780470689592.ch11

Cited by 4 publications

(5 citation statements)

References 45 publications

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“…At higher material densities, which were generated by forming compacts on a Carver Press, the LIF signal decreased with increasing density. This quenching phenomenon has been ascribed to competing excited state processes, interacting species, and sample matrix effects that can lead to a decrease in LIF response (5). A statistically significant MD-API% w/w interaction was also observed in this earlier study.…”

Section: Resultssupporting

confidence: 59%

“…where I f is the fluorescent intensity, P o the incident irradiance or power per unit area, γ the fluorescent collection efficiency, ϕ the fluorophore quantum efficiency, ε the molar absorptivity at the fluorophore excitation wavelength, b the optical path length, and C the concentration of the fluorophore (5). The fluorescent intensity equation shows that fluorescent intensity response is directly proportional to the incident irradiance.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Percent Relative Humidity, Moisture Content, and Compression Force on Light-Induced Fluorescence (LIF) Response as a Process Analytical Tool

Shah

Stagner

2015

AAPS PharmSciTech

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Abstract. The effect of percent relative humidity (16-84% RH), moisture content (4.2-6.5% w/w MC), and compression force (4.9-44.1 kN CF) on the light-induced fluorescence (LIF) response of 10% w/w active pharmaceutical ingredient (API) compacts is reported. The fluorescent response was evaluated using two separate central composite designs of experiments. The effect of % RH and CF on the LIF signal was highly significant with an adjusted R 2 =0.9436 and p<0.0001. Percent relative humidity (p=0.0022), CF (p<0.0001), and % RH 2 (p=0.0237) were statistically significant factors affecting the LIF response. The effects of MC and CF on LIF response were also statistically significant with a p value <0.0001 and adjusted R 2 value of 0.9874. The LIF response was highly impacted by MC (p<0.0001), CF (p<0.0001), and MC 2 (p=0022). At 10% w/w API, increased % RH, MC, and CF led to a nonlinear decrease in LIF response. The derived quadratic model equations explained more than 94% of the data. Awareness of these effects on LIF response is critical when implementing LIF as a process analytical tool.KEY WORDS: design of experiments (DOE); fluorescence quenching; light-induced fluorescence (LIF); moisture; process analytical technology (PAT).

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Section: Resultssupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Effect of Percent Relative Humidity, Moisture Content, and Compression Force on Light-Induced Fluorescence (LIF) Response as a Process Analytical Tool

Shah

Stagner

2015

AAPS PharmSciTech

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“…This phenomena has been discussed in some detail and is ascribed to competing excited state processes, interacting species, and sample matrix effects that can lead to a decrease in LIF response. 28,29 Determination of the mechanism for the negative parabolic bending was beyond the scope of the aim of this research. However, the possibility of photobleaching was evaluated and it was shown to not occur in the samples studied.…”

Section: Effect Of Tapped Density Compacted Density and Api Concentmentioning

confidence: 99%

“…where I f is the fluorescent intensity, P 0 is the incident irradiance or power per unit area, ( is the fluorescent collection efficiency, N is the fluorophore quantum efficiency, g is the molar absorptivity at the fluorophore excitation wavelength, b is the optical path length, C is the concentration of the fluorophore, and k is the proportionality constant. [28][29][30] Equation (1) states that within limits, increasing the incident excitation irradiance results in a proportional increase in fluorescence intensity. This gives additional detection flexibility and an advantage for LIF process analysis.…”

Section: Introductionmentioning

confidence: 99%

Effect of Tapped Density, Compacted Density, and Drug Concentration on Light-Induced Fluorescence Response as a Process Analytical Tool

Shah

Ely

Stagner

2015

Journal of Pharmaceutical Sciences

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“…This effect results in exceptional sensitivity with very low detection limits as well as a wide dynamic range. Moreover, fluorescence spectroscopy has fast response times and the capability of remote sensing . Therefore, this method is perfectly suited for in‐line PAT applications.…”

Section: Introductionmentioning

confidence: 99%

A novel LED‐based 2D‐fluorescence spectroscopy system for in‐line monitoring of Chinese hamster ovary cell cultivations – Part I

Graf

Claßen²,

Solle³

et al. 2019

Engineering in Life Sciences

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A new two‐dimensional fluorescence sensor system was developed for in‐line monitoring of mammalian cell cultures. Fluorescence spectroscopy allows for the detection and quantification of naturally occurring intra‐ and extracellular fluorophores in the cell broth. The fluorescence signals correlate to the cells’ current redox state and other relevant process parameters. Cell culture pretests with twelve different excitation wavelengths showed that only three wavelengths account for a vast majority of spectral variation. Accordingly, the newly developed device utilizes three high‐power LEDs as excitation sources in combination with a back‐thinned CCD‐spectrometer for fluorescence detection. This setup was first tested in a lab design of experiments study with process relevant fluorophores proving its suitability for cell culture monitoring with LOD in the μg/L range. The sensor was then integrated into a CHO‐K1 cell culture process. The acquired fluorescence spectra of several batches were evaluated using multivariate methods. The resulting batch evolution models were challenged in deviating and “golden batch” validation runs. These first tests showed that the new sensor can trace the cells’ metabolic state in a fast and reliable manner. Cellular distress is quickly detected as a deviation from the “golden batch”.

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Fluorescent Sensing and Process Analytical Applications

Cited by 4 publications

References 45 publications

Effect of Percent Relative Humidity, Moisture Content, and Compression Force on Light-Induced Fluorescence (LIF) Response as a Process Analytical Tool

Effect of Percent Relative Humidity, Moisture Content, and Compression Force on Light-Induced Fluorescence (LIF) Response as a Process Analytical Tool

Effect of Tapped Density, Compacted Density, and Drug Concentration on Light-Induced Fluorescence Response as a Process Analytical Tool

A novel LED‐based 2D‐fluorescence spectroscopy system for in‐line monitoring of Chinese hamster ovary cell cultivations – Part I

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