Small-volume extensional rheology of concentrated protein and protein-excipient solutions

Lauser, Kathleen T.; Rueter, Amy L.; Calabrese, Michelle A.

doi:10.1039/d1sm01253c

Cited by 21 publications

(72 citation statements)

References 78 publications

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“…Here, (GR 0 /2σ ) 1/3 is treated as a fitting constant, as is commonly done. 23,36 The extracted extensional relaxation times λ E for PEO solutions in water are statistically similar for measurements taken inside and outside of the environmental control chamber (Figure 2a, Tables 1, S1), and are in quantitative agreement with previously published DoS results. 23,36 These prior studies did not incorporate environmental control, suggesting that ambient conditions are sufficient for measuring dilute aqueous polymers via DoS.…”

Section: Validation Of Vdos Device With Peo In Various Solventssupporting

confidence: 87%

“…A dripping-onto-substrate device consists of a dispensing system to extrude the drop which forms the liquid bridge and an imaging system to precisely measure the thinning profile of the bridge at high speed (Figure 1). 36 ; see SI.2. To perform DoS measurements, the syringe pump is used to extrude a droplet from a needle with radius R 0 , which then forms a liquid bridge with height h upon contact with the substrate.…”

Section: Results Vdos Environmental Chamber Developmentmentioning

confidence: 99%

“…This technique enables measurement of complex fluids in small volumes (∼10 µL), reducing use of expensive sample components, mitigating pre-deformation, and minimizing inertial effects, which allows for the measurement of low surface-tension, low-viscosity systems. By directly mounting the syringe above the substrate, 36 contact between the sample and excess tubing used in the standard DoS instrumentation 23,32 can be eliminated, preventing leaching issues from the use of organic solvents and further reducing sample volume. However, the small volume and high surface area-to-volume ratio of the drop exacerbates evaporation effects in volatile systems, and current DoS instrumentation to-date has not employed environmental control.…”

Section: Introductionmentioning

confidence: 99%

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Volatile dripping onto substrate (vDoS) extensional rheology of viscoelastic polymer solutions

Robertson

Calabrese

2021

Preprint

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Extensional flow properties of volatile polymer solutions govern many industrially-relevant coating processes, but existing instrumentation lacks the environmental control necessary to control evaporation. To mitigate evaporation during volatile dripping-onto-substrate (vDoS) extensional rheology measurements, we developed a chamber to enclose the sample in an environment saturated with solvent vapor. We validated the vDoS device by measuring a model high molecular weight polyethy-lene oxide (PEO) in various organic solvents both inside and outside of the chamber. Evaporation substantially increased the extensional relaxation time λ E for PEO in volatile solvents like dichloromethane (DCM) and chloroform. PEO/chloroform solutions displayed an over 20-fold increase in λ E due to the formation of an evaporation-induced surface film; evaporation studies confirmed surface features and skin formation reminiscent of buckling instabilities commonly observed during drying in polymer solutions. Finally, the relaxation times of semi-dilute PEO/chloroform solutions were measured with environmental control, where λ E scaled with concentration by the exponent m=0.62. These measurements validate the vDoS device by confirming that chloroform is a good solvent for PEO, with a Flory exponent of ν=0.54. Our results demonstrate the first environmental control of evaporation during DoS extensional rheology, and provide guidelines establishing when environmental control is necessary to obtain accurate rheological parameters.

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Section: Validation Of Vdos Device With Peo In Various Solventssupporting

confidence: 87%

Section: Results Vdos Environmental Chamber Developmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Volatile dripping onto substrate (vDoS) extensional rheology of viscoelastic polymer solutions

Robertson

Calabrese

2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…This technique enables measurement of complex fluids in small volumes ( 10 L), reducing use of expensive sample components, mitigating pre-deformation, and minimizing inertial effects, which allows for the measurement of low surface-tension, low-viscosity systems. By directly mounting the syringe above the substrate 38 , contact between the sample and excess tubing used in the standard DoS instrumentation 23 , 32 can be eliminated, preventing leaching issues from the use of organic solvents and further reducing sample volume. However, the small volume and high surface area-to-volume ratio of the drop exacerbates evaporation effects in volatile systems, and DoS instrumentation to-date has not employed true environmental control 5 , 23 , 38 , 39 .…”

Section: Introductionmentioning

confidence: 99%

“…By directly mounting the syringe above the substrate 38 , contact between the sample and excess tubing used in the standard DoS instrumentation 23 , 32 can be eliminated, preventing leaching issues from the use of organic solvents and further reducing sample volume. However, the small volume and high surface area-to-volume ratio of the drop exacerbates evaporation effects in volatile systems, and DoS instrumentation to-date has not employed true environmental control 5 , 23 , 38 , 39 .…”

Section: Introductionmentioning

confidence: 99%

Evaporation-controlled dripping-onto-substrate (DoS) extensional rheology of viscoelastic polymer solutions

Robertson

Calabrese

2022

Sci Rep

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Extensional flow properties of polymer solutions in volatile solvents govern many industrially-relevant coating processes, but existing instrumentation lacks the environment necessary to control evaporation. To mitigate evaporation during dripping-onto-substrate (DoS) extensional rheology measurements, we developed a chamber to enclose the sample in an environment saturated with solvent vapor. We validated the evaporation-controlled DoS device by measuring a model high molecular weight polyethylene oxide (PEO) in various organic solvents both inside and outside of the chamber. Evaporation substantially increased the extensional relaxation time $$\lambda _{E}$$ λ E for PEO in volatile solvents like dichloromethane and chloroform. PEO/chloroform solutions displayed an over 20-fold increase in $$\lambda _{E}$$ λ E due to the formation of an evaporation-induced surface film; evaporation studies confirmed surface features and skin formation reminiscent of buckling instabilities commonly observed in drying polymer solutions. Finally, the relaxation times of semi-dilute PEO/chloroform solutions were measured with environmental control, where $$\lambda _{E}$$ λ E scaled with concentration by the exponent $$m=0.62$$ m = 0.62 . These measurements validate the evaporation-controlled DoS environment, and confirm that chloroform is a good solvent for PEO, with a Flory exponent of $$\nu =0.54$$ ν = 0.54 . Our results are the first to control evaporation during DoS extensional rheology, and provide guidelines establishing when environmental control is necessary to obtain accurate rheological parameters.

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Polysorbate identity and quantity dictate the extensional flow properties of protein‐excipient solutions

2022

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While protein medications are promising for treatment of cancer and autoimmune diseases, challenges persist in terms of development and injection stability of highconcentration formulations. Here, the extensional flow properties of proteinexcipient solutions are examined via dripping-onto-substrate extensional rheology, using a model ovalbumin (OVA) protein and biocompatible excipients polysorbate 20 (PS20) and 80 (PS80). Despite similar PS structures, differences in extensional flow are observed based on PS identity in two regimes: at moderate total concentrations where surface tension differences drive changes in extensional flow behavior, and at small PS:OVA ratios, which impact the onset of weakly elastic flow behavior.Undesirable elasticity is observed in ultra-concentrated formulations, independent of PS identity; higher PS contents are required to observe these effects than in analogous polymeric excipient solutions. These studies reveal novel extensional flow behaviors in protein-excipient solutions, and provide a straightforward methodology for assessing the extensional flow stability of new protein-excipient formulations.

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Small-volume extensional rheology of concentrated protein and protein-excipient solutions

Abstract: Limited studies measure extensional rheology in protein solutions due to volume constraints and measurement challenges. We developed a small-volume, Dripping-onto-Substrate (DoS) extensional rheology device to measure the capillary thinning of...

Cited by 21 publications

References 78 publications

Volatile dripping onto substrate (vDoS) extensional rheology of viscoelastic polymer solutions

Volatile dripping onto substrate (vDoS) extensional rheology of viscoelastic polymer solutions

Evaporation-controlled dripping-onto-substrate (DoS) extensional rheology of viscoelastic polymer solutions

Polysorbate identity and quantity dictate the extensional flow properties of protein‐excipient solutions

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