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Targeted microbubbles (TMBs) that specifically accumulate on target sites via biochemical bonds have been studied for using ultrasound diagnoses and therapies (e.g., ultrasound molecular imaging) in the research field. To understand the specific interactions between TMBs and their target molecules, a biosensor system with a quartz crystal microbalance (QCM) was constructed. In this system, TMBs become absorbed on their target molecule, which was fixed to the QCM surface via a self-assembled monolayer. Our previous studies showed that the system allowed the evaluation of the interaction between biotinylated MBs and the target molecule, streptavidin, by monitoring changes in the resonant frequency of QCM [Muramoto et al., Ultrasound Med. Biol., 40(5), 1027–1033 (2014)]. This paper investigates how the amount of streptavidin relates to the amount of absorbed biotinylated MBs. The amount of streptavidin on the QCM surface was evaluated by measuring the difference in its resonant frequency before and after the fixation of streptavidin. After which, the amount of absorbed MBs was also evaluated by measuring the frequency shift during the interaction between MBs and the target molecule. Our results showed a weak correlation between the amounts of bound MB and the density of streptavidin (correlation coefficient, r = 0.44), suggesting that the area density of target molecule can be evaluated by estimating the number density of TMBs.

We achieved the bottom-up via-filling by copper electrodeposition using a single diallylamine-type copolymer additive instead of the four types of additives, Suppressor Leveler Accelerator and Chloride ions. We newly synthesized and used four additives modified side chains to research more the function of this additive. We observed vias cross sections, performed an electrochemical analysis and conducted quartz crystal microbalance (QCM) measurements. By comparing the amino group at the end of the side chain with the one near the main chain, it was found the basicity of the latter is weak due to the neighboring group effect. However, when the distance between these two amino groups is long, the basicity of the amino group near the main chain is strong. The use of a polymer additive with a strong amino group near the main chain had the effect of suppressing the electrodeposition outside vias and achieving a good bottom-up filling.

Targeted microbubbles can accumulate in the targeting site via a biochemical reaction. We propose a system for evaluating the accumulation of the bubbles using a quartz crystal microbalance (QCM) as the thickness shear-mode resonator. We derive the formula of the electrical admittance of QCM for the load of bubbles by modeling the reaction force generated by the specifically adsorbed bubbles. The bubble-load model enabled the calculation of the number density of the adsorbed bubbles on the QCM surface. A comparison with experimental results showed that the proposed system yields the possibility of quantitatively estimating the number density. This system will help us to develop new targeted microbubbles.

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