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  1. Ultrafast affinity extraction (UAE) is a form of microscale affinity HPLC that can be employed to quickly measure equilibrium constants for solute-binding agent interactions in solution. This study used chromatographic and equilibrium theory with universal plots to examine the general conditions that are needed in UAE to obtain accurate, precise, and robust measurements of equilibrium constants for such interactions. The predicted results were compared to those obtained by UAE in studies that examined the binding of various drugs with two transport proteins: human serum albumin and α1-acid glycoprotein. The most precise and robust conditions for these binding studies occurred for systems with intermediate values for their equilibrium free fraction for the solute (F0 ≈ 0.20-0.80). These trends showed good agreement with those seen in prior studies using UAE. It was further determined how the apparent free fraction of a solute was related to the dissociation rate of this solute, the time allowed for solute dissociation during UAE, and the equilibrium free fraction for the solute. These results also agreed with experimental results, as obtained for the binding of warfarin and gliclazide with human serum albumin. The final section examined how a change in the apparent free fraction, as caused by solute dissociation, affected the accuracy of an equilibrium constant that was measured by UAE. In addition, theoretical plots were generated to allow the selection of conditions for UAE that provided a given level of accuracy during the measurement of an equilibrium constant. The equations created and trends identified for UAE were general ones that can be extended in future work to other solutes and binding agents. 
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    Free, publicly-accessible full text available September 1, 2024
  2. Abstract

    Ultrasound is a safe, noninvasive diagnostic technique used to measure internal structures such as tissues, organs, and arterial and venous blood flow. Skin‐mounted wearable ultrasound devices can enable long‐term continuous monitoring of patients to provide solutions to critical healthcare needs. However, stretchable ultrasound devices that are composed of ultrasonic transducers embedded in an elastomer matrix are incompatible with existing rigid acoustic matching layers, leading to reduced energy transmission and reduced imaging resolution. Here, a systematic study of soft composites with liquid metal (LM) fillers dispersed in elastomers reveals key strategies to tune the acoustic impedance of soft materials. Experiments supported by theoretical models demonstrate that the increase in acoustic impedance is primarily driven by the increase in density with negligible changes to the speed of sound through the material. By controlling the volume loading and particle size of the LM fillers, a material is created that achieves a high acoustic impedance 4.8 Mrayl, (> 440% increase over the polymer matrix) with low modulus (< 1 MPa) and high stretchability (> 100% strain). When the device is mechanically strained, a small decrease is observed in acoustic impedance (< 15%) with negligible decrease in sound transmittance and impact on attenuation for all droplet sizes. The stretchable acoustic matching layer is then integrated with a wearable ultrasound device and the ability to measure motion is demonstrated using a phantom model as is performed in Doppler ultrasound.

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