The use of blood samples as liquid biopsy is a label-free method for cancer diagnosis that offers benefits over traditional invasive biopsy techniques. Cell sorting by acoustic waves offers a means to separate rare cells from blood samples based on their physical properties in a label-free, contactless and biocompatible manner. Herein, we describe a flow-through separation approach that provides an efficient separation of tumor cells (TCs) from white blood cells (WBCs) in a microfluidic device, “THINUS-Chip” (Thin-Ultrasonic-Separator-Chip), actuated by ultrasounds. We introduce for the first time the concept of plate acoustic waves (PAW) applied to acoustophoresis as a new strategy. It lies in the geometrical chip design: different to other microseparators based on either bulk acoustic waves (BAW) or surface waves (SAW, SSAW and tSAW), it allows the use of polymeric materials without restrictions in the frequency of work. We demonstrate its ability to perform high-throughput isolation of TCs from WBCs, allowing a recovery rate of 84% ± 8% of TCs with a purity higher than 80% and combined viability of 85% at a flow rate of 80 μL/min (4.8 mL/h). The THINUS-Chip performs cell fractionation with low-cost manufacturing processes, opening the door to possible easy printing fabrication.
A novel experimental technique based on phase spectroscopy and through transmission of high-frequency airborne ultrasonic pulses is used to study rigid open cell foams. Phase velocity shows an anomalous relaxation like behavior which is attributed to a frequency variation of the apparent tortuosity. An explanation is proposed in terms of the relationship between the different length scales involved: microstructure and macroscopic behavior. The experimental technique together with the proposed apparent tortuosity scheme provides a novel and unique procedure to determine simultaneously tortuosity and characteristic length dimension and shape of the solid constituent of foams and porous materials in general.
The choice of substrate material in a chip that combines ultrasound with microfluidics for handling biological and synthetic microparticles can have a profound effect on the performance of the device. This is due to the high surface-to-volume ratio that exists within such small structures and acquires particular relevance in polymer-based resonators with 3D standing waves. This paper presents three chips developed to perform particle flow-through separation by ultrasound based on a polymeric SU-8 layer containing channelization over three different substrates: Polymethyl methacrylate (PMMA); Pyrex; and a cracked PMMA composite-like structure. Through direct observations of polystyrene microbeads inside the channel, the three checked chips exhibit their potential as disposable continuous concentration devices with different spatial pressure patterns at frequencies of resonance close to 1 Mhz. Chips with Pyrex and cracked PMMA substrates show restrictions on the number of pressure nodes established in the channel associated with the inhibition of 3D modes in the solid structure. The glass-substrate chip presents some advantages associated with lower energy requirements to collect particles. According to the results, the use of polymer-based chips with rigid substrates can be advantageous for applications that require short treatment times (clinical tests handling human samples) and low-cost fabrication.
Wide-band and air-coupled ultrasound pulses are propagated through slabs of open-cell reticulated solid foams and the transmission coefficient is measured. Under these conditions, fluid in the pores and solid skeleton are strongly decoupled; in addition, at frequencies well over that of the relaxation of the influence of the tortuosity, it is observed that energy loss approaches to a constant value: . Internal surface area and the length dimension parameter of the foams are independently measured. Results reveal that vs or follows a power law very close to linear, suggesting a possible spatial normalization for .
Acoustophoretic blood plasma separation is based on cell enrichment processes driven by acoustic radiation forces. The combined influence of hematocrit and hydrodynamics has not yet been quantified in the literature for these processes acoustically induced on blood. In this paper, we present an experimental study of blood samples exposed to ultrasonic standing waves at different hematocrit percentages and hydrodynamic conditions, in order to enlighten their individual influence on the acoustic response of the samples. The experiments were performed in a glass capillary (700 µm-square cross section) actuated by a piezoelectric ceramic at a frequency of 1.153 MHz, hosting 2D orthogonal half-wavelength resonances transverse to the channel length, with a single-pressure-node along its central axis. Different hematocrit percentages Hct = 2.25%, 4.50%, 9.00%, and 22.50%, were tested at eight flow rate conditions of Q = 0:80 µL/min. Cells were collected along the central axis driven by the acoustic radiation force, releasing plasma progressively free of cells. The study shows an optimal performance in a flow rate interval between 20 and 80 µL/min for low hematocrit percentages Hct ≤ 9.0%, which required very short times close to 10 s to achieve cell-free plasma in percentages over 90%. This study opens new lines for low-cost personalized blood diagnosis.
This paper describes the effects of low intensity continuous ultrasound (LICU) on the inflammatory response of mouse pancreatic tumor explants. While there are many reports focusing on the application of low-intensity pulsed ultrasound (LIPUS) on cell cultures and tissues, the effects of continuous oscillations on biological tissues have never been investigated. Here we present an exploratory study of the effects induced by LICU on mouse pancreatic tumor explants. We show that LICU causes significant upregulation of IFN-γ, IL-1β, and TNF-α on tumor explants. No detectable effects were observed on tumor vasculature or collagen I deposition, while thermal and mechanical effects were not apparent. Tumor explants responded as a single unit to acoustic waves, with spatial pressure variations smaller than their size.