The use of bulk nanobubbles in biomedicine is increasing in recent years. This translates into new opportunities for microfluidics, which may enable the generation of higher quality nanobubbles that lead to advances in diagnostics and therapeutics.
Monodisperse microbubbles with diameters less than 10 μm are desirable in several ultrasound imaging and therapeutic delivery applications. However, conventional approaches to synthesize microbubbles, which are usually agitation-based, produce polydisperse bubbles that are less desirable because of their heterogeneous response when exposed to an ultrasound field. Microfluidics technology has the unique advantage of generating size-controlled monodisperse microbubbles, and it is now well established that the diameter of microfluidically made microbubbles can be tuned by varying the liquid flow rate, gas pressure, and dimensions of the microfluidic channel. It is also observed that once the microbubbles form, the bubbles shrink and eventually stabilize to a quasi-equilibrium diameter, and that the rate of stabilization is related to the lipid solution. However, how the lipid solution concentration affects the degree of bubble shrinkage, and the stable size of microbubbles, has not been thoroughly examined. Here, we investigate whether and how the lipid concentration affects the degree of microbubble shrinkage. Namely, we utilize a flow-focusing microfluidic geometry to generate monodisperse bubbles, and observe the effect of gas composition (2.5, 1.42, and 0.17 wt % octafluoropropane in nitrogen) and lipid concentration (1−16 mg/mL) on the degree of microbubble shrinkage. For the lipid system and gas utilized in these experiments, we observe a monotonic increase in the degree of microbubble shrinkage with decreasing lipid concentration, and no dependency on the gas composition. We hypothesize that the degree of shrinkage is related to lipid concentration by the self-assembly of lipids on the gas−liquid interface during bubble generation and subsequent lipid packing on the interface during shrinkage, which is arrested when a maximum packing density is achieved. We anticipate that this approach for creating and tuning the size of monodisperse microbubbles will find utility in biomedical applications, such as contrast-enhanced ultrasound imaging and ultrasound-triggered gene delivery.
In this paper, a nozzle-diffuser electromagnetic micropump with nanocomposite magnetic membrane for sub-microliter pumping applications is presented. The membrane included magnetite (Fe3O4) nanoparticles dispersed in a layer of polydimethylsiloxane (PDMS). Fe3O4 as a nontoxic and environmentally friendly material with excellent magnetic properties is used for the first time in the fabrication of an electromagnetic micropump. In order to achieve the most biocompatibility, PDMS is applied in most parts of the micropump. Lack of control on the recovery time of the membrane is one of the most important disadvantages of the proposed micropumps in the literature. This weakness causes an imbalance between the supply and pump mode of the micropumps leading to an undesirable performance of both of these. To address this issue, a bidirectional electromagnetic micropump is presented in this paper. In this system a secondary magnetic field is applied to equalize the response and recovery time of the membrane. Using this novel micropump, the maximum flow rate of 1.25 µl min−1 at the frequency of 0.1 Hz has been achieved. To indicate the best performance conditions for the micropump, effective parameters on the micropump performance were examined. These parameters include the size of the microchannels, electric current, number of coil turns, concentration of the Fe3O4 nanoparticles and frequency.
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