Whole-blood sorting, enrichment and in situ immunolabeling of cellular subsets using acoustic microstreaming

Abstract

Analyzing undiluted whole human blood is a challenge due to its complex composition of hematopoietic cellular populations, nucleic acids, metabolites, and proteins. We present a novel multi-functional microfluidic acoustic streaming platform that enables sorting, enrichment and in situ identification of cellular subsets from whole blood. This single device platform, based on lateral cavity acoustic transducers (LCAT), enables (1) the sorting of undiluted donor whole blood into its cellular subsets (platelets, RBCs, and WBCs), (2) the enrichment and retrieval of breast cancer cells (MCF-7) spiked in donor whole blood at rare cell relevant concentrations (10 mL − 1 ), and (3) on-chip immunofluorescent labeling for the detection of specific target cellular populations by their known marker expression patterns. Our approach thus demonstrates a compact system that integrates upstream sample processing with downstream separation/enrichment, to carry out multi-parametric cell analysis for blood-based diagnosis and liquid biopsy blood sampling.

Sonoporation of Cells by a Parallel Stable Cavitation Microbubble Array

“…Ward et al demonstrated that the percentage of sonoporated cells is proportional to the cubic power of the microbubblecell spacing. [59,60] Additionally, the air microbubble generated by the air/liquid interface without a shell used in this study can oscillate freely, making the sonoporation more efficient. By combining the secondary acoustic radiation force and the drag force induced by microstreaming, a single cell can be trapped at the microbubble surface at a trapping rate of up to 95.50 ± 2.78% (Figure 5b).…”

Vibrational modes prediction for water-air bubbles trapped in circular microcavities

“…As can be seen from (28), it is dependent on the bubble size, distance between the bubble centers, and damping factors of the bubbles. The dependence of non-dimensional (with respect to the resonant frequency of a single bubble) resonant frequency from the non-dimensional bubble radius (with respect to the distance between the bubble centers) is given in Fig.…”

“…3,[12][13][14][15] Other applications of oscillating bubbles to be mentioned are micropumps, 16 microtweezers, [17][18][19] microfilters, 20 microrotors, 21 biosensors, 22 microswimmers, [23][24][25] and sorting. [26][27][28] An extensive literature exists on theoretical predication of dynamics as well as resonant and dissipative behavior of spherical bubbles, capitalizing on the well-known Minnaert 29 frequency. The dynamics of spherical bubbles that are either free or confined inside a cavity has been studied for more than a century, starting from the seminal work of Rayleigh 30 and followed by Plesset 31 and others.…”

Hypersonic‐Induced 3D Hydrodynamic Tweezers for Versatile Manipulations of Micro/Nanoscale Objects

“…Nevertheless, HTs trap particles in static immobilization and cannot selectively transport individual objects, preventing their further development for complex applications. Inspired by the hydrodynamic methods, streaming effect induced by optic‐heat, and acoustics has been explored to develop noncontact microrobots. Especially, acoustic streaming, which arises from the nonlinear propagation of a compression wave through an attenuating media, has been studied as a promising approach for micro/nano manipulation, since it can artificially induce fluid flow where velocity can be tuned independently of the flow rate.…”

“…The 3D‐VSA is highly localized with rapid‐rotating velocity, enabling an excellent trapping capability for different sized particles ranged from micrometers to sub‐100 nm. Different from the planar vortices generated by acoustic bubbles or focused SAWs, the 3D‐VSA generated in the HSHT has a rotation axis parallel to the substrate, of which the formation can be well tuned with the applied flow rate, forming the basis for size‐selective trapping and multifunctional manipulations of micro/nanoscale objects. Meanwhile, under the viscous driving force, the trapped particles can be rotated at the equilibrium positions.…”