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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. 

Abstract Ultrasound is a safe, noninvasive diagnostic technique used to measure internal structures such as blood vessels and the velocity of blood flow in the human body. The ability to continuously measure blood flow in major cerebral arteries would enable the early detection of medical problems such as stroke. However, current ultrasound technology consists of rigid, hand-held probes that are arduous to use, sensitive to movement, and are primarily designed for intermittent, instead of continuous use. Here, we describe the design of a wearable ultrasound patch for continuously measuring blood flow velocity through the middle cerebral artery (MCA) that can be assessed from the temple region of the head. The wearable ultrasound patch is composed of an array of piezoelectric elements that are wired together using flexible electrical conductors and encapsulated in an elastic substrate. To improve ultrasound energy transfer, a soft and conformal composite matching layer is introduced. The matching layer consists of gallium-based liquid metal (LM) microdroplets dispersed in a silicone elastomer. The acoustic impedance of the matching layer can be tuned by varying the volume loading of LM. The wearable ultrasound patch will provide new opportunities to continuously measure blood flow velocity and ultimately enable early detection of medical problems such as stroke.