Measuring sample Viscosity? - Essential parameter in Biophysical Analysis, Drug Formulation and Bioprocessing

This article from FIDA QC series delves into the critical role of viscosity measurement and control in Biophysical Analysis, Drug Formulation and Bioprocessing. Furthermore, we explore how advancements in Flow Induced Dispersion Analysis (FIDA) provide precise measurement and automated viscosity correction, which enhance the understanding of viscosity's impact on experimental results and process optimisation.

Biophysical Analysis

Many biophysical analytical methods are directly or indirectly dependent on or affected by changes in diffusion. This includes, amongst others, DLS, SPR, NMR, Small-Angle X-ray, chromatography, and Cryo-EM, to mention a few. Even with ELISA assays, if the sample has high viscosity or contains large aggregates, diffusion of the target molecules within the sample matrix may be slower, potentially leading to longer incubation times or incomplete binding.

Viscosity affects the rate of diffusion of molecules and particles. And thereby, all technologies that are directly or indirectly dependent on or affected by changes in diffusion must also be observant towards the actual viscosity of the sample to be analysed.

One thing is the situation where you are aware of a viscosity change. Then in most cases, there are ways to mitigate this. In SPR, it is well known that high viscosity may influence mass transport and reduce the rate at which target molecules reach the sensor and thereby changing the relative impact of mass transport over kinetics.  This may be partially mitigated by calibrating the system using reference samples with known viscosity values or using mathematical models to account for (known) viscosity effects.

The more significant problem occurs when a viscosity change is not realised up front and thereby not mitigated, where the data cannot be analysed or the wrong interpretation is made.

Drug formulation

Viscosity is essential in drug formulation. It affects multiple aspects of the product's performance, stability, and administration.

1. Product Stability: Viscosity impacts the biophysical properties of formulations in general. And when working with suspensions or emulsions, it is essential to control viscosity to ensure uniform dispersion of the drug throughout the formulation, preventing sedimentation or managing phase separation.
2. Drug Release and Bioavailability: Viscosity may impact the release and bioavailability of drugs from pharmaceutical formulations. For example, viscosity affects the dissolution rate (through diffusivity) in oral drug delivery, which can influence the drug's absorption in the gastrointestinal tract.
3. Injection and Infusion: Monitoring viscosity is important to control the injectability of the drug, needle flow and ease of administration.

Bioprocessing

Correct determination and control of viscosity throughout the bioprocessing workflow are crucial for achieving desired process outcomes, maintaining product quality, and ensuring the safety and efficacy of biopharmaceutical products. The importance of this measurement is especially clear in production of biological products such as vaccines, recombinant proteins, monoclonal antibodies, and other biopharmaceuticals.

1. Fermentation: Viscosity affects the growth and productivity of cells in bioreactors during cell culture and fermentation. High viscosity can impact mass transfer, nutrient availability, and oxygen supply to the cells, potentially leading to reduced cell growth and lower protein production.
2. Filtration and Separation: Viscosity impacts the filtration efficiency and separation processes used to purify biopharmaceutical products. High viscosity can lead to increased fouling of filters, reduced flow rates, and decreased process performance.
3. Product Stability and Shelf Life: Viscosity can impact biopharmaceutical products' stability and shelf life. High-viscosity formulations may exhibit increased susceptibility to aggregation, precipitation, or physical instability.

Determination and control of viscosity throughout the bioprocessing workflow is crucial for achieving desired process outcomes, maintaining product quality, and ensuring the safety and efficacy of biopharmaceutical products.

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FIDA and viscosity

In Flow Induced Dispersion Analysis, changes in viscosity also impact the result. However, compared to other platforms, the correction for viscosity change is automatically built into every FIDA measurement (incl. binding studies, stability studies, and quantifications). In other words, you do not need to correct anything manually, and the data is correct even if there are unexpected viscosity changes.

‍In every FIDA measurement, the viscosity is calculated based on the time lapse from sample introduction in the capillary till it reaches the detector (the peak point). Thereby, the Fida 1 can also be used as a very accurate viscosity meter capable of measuring viscosities from 0.89 cP up to +20 cP with an ability to measure changes as low as 0.2 cP. On top of that, in Fida 1 instrument, temperature-induced viscosity changes are managed thanks to its built-in temperature control.

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Gaining an edge

By using advanced viscosity measurement techniques, you can gain a competitive edge in your field and ensure the highest level of data integrity. Embrace this cutting-edge technology to elevate your research and stay at the forefront of scientific discovery. Don't miss the opportunity to leverage this groundbreaking capability and revolutionise your understanding of viscosity in biophysical analysis, drug formulation, and bioprocessing read more about quality control with Fida 1.

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