There has been increasing evidence that micro and messenger RNA derived from exosomes play important roles in pancreatic and other cancers. In this work, a microfluidics-based approach to the analysis of exosomal RNA is presented based on surface acoustic wave (SAW) exosome lysis and ion-exchange nanomembrane RNA sensing performed in conjunction on two separate chips. Using microRNA hsa-miR-550 as a model target and raw cell media from pancreatic cancer cell lines as a biological sample, SAW-based exosome lysis is shown to have a lysis rate of 38%, and an ion-exchange nanomembrane sensor is shown to have a limit of detection of 2 pM, with two decades of linear dynamic range. A universal calibration curve was derived for the membrane sensor and used to detect the target at a concentration of 13 pM in a SAW-lysed sample, which translates to 14 target miRNA per exosome from the raw cell media. At a total analysis time of ~1.5 h, this approach is a significant improvement over existing methods that require two overnight steps and 13 h of processing time. The platform also requires much smaller sample volumes than existing technology (~100 μL as opposed to ~mL) and operates with minimal sample loss, a distinct advantage for studies involving mouse models or other situations where the working fluid is scarce.

No abstract

A planar surface acoustic wave on a solid substrate and its radiated sound into a static liquid drop produce time-averaged, exponentially decaying acoustic and electric Maxwell pressures near the contact line. These localized contact-line pressures are shown to generate two sequences of hemispherical satellite droplets at the tens of microns and submicron scales, both obeying self-similar exponential scaling but with distinct exponents that correspond to viscous dissipation and field leakage length scales, respectively. The acoustic pressure becomes dominant when the film thickness exceeds (1/4π) of the surface acoustic wave wavelength and it affects the shape and stability of the mother drop. The Maxwell pressure of the nanodrops, which exceeds ten atmospheres, is sensitive to the contact angle.

The exponentially decaying acoustic pressure of scattered surface acoustic waves (SAWs) at the contact line of a liquid film pinned to filter paper is shown to sustain a high curvature conic tip with micron-sized modulations whose dimension grows exponentially from the tip. The large negative capillary pressure in the film, necessary for offsetting the large positive acoustic pressure at the contact line, also creates significant negative hydrodynamic pressure and robust wicking action through the paper. An asymptotic analysis of this intricate pressure matching between the quasistatic conic film and bulk drop shows that the necessary SAW power to pump liquid from the filter paper and aerosolize, expressed in terms of the acoustic pressure scaled by the drop capillary pressure, grows exponentially with respect to twice the acoustic decay constant multiplied by the drop length, with a universal preexponential coefficient. Global rapid aerosolization occurs at a SAW power twice as high, beyond which the wicking rate saturates.

Due to viscous decay, a planar surface acoustic wave (SAW) diffracting from a solid substrate into a liquid film produces a time-averaged, exponentially decaying acoustic pressure in the film. We show that if the film is pinned against a bounding wall, the localized acoustic pressure generates a sequence of surface drops at the contact line, whose dimensions decay in the same exponential manner as the localized acoustic pressure. The undulating interfacial profile near the contact line also inherits this exponential decay, such that the averaged contact angle is exponentially small. The bulk film topology and the aerosolization mechanism are hence insensitive to the wettability of the surface but are controlled only by the localized acoustic pressure and the decaying undulations it produces at the contact line. The size distribution of surface drops is collapsed under the exponential scaling that depends only on the SAW decay rate and amplitude. Numerical modeling based on the Young-Laplace equation is used to model the liquid profile and to predict two aerosolization regimes.