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Multiplex separation of mixed biological samples is essential in a considerable portion of biomedical research and clinical applications. An automated and operator-independent process for the separation of samples is highly sought after. There is a significant unmet need for methods that can perform fractionation of small volumes of multicomponent mixtures. Herein, we design an integrated chip that combines acoustic and electric fields to enable efficient and label-free separation of multiple different cells and particles under flow. To facilitate the connection of multiple sorting mechanisms in tandem, we investigate the electroosmosis (EO)-induced deterministic lateral displacement (DLD) separation in a combined pressure- and DC field-driven flow and exploit the combination of the bipolar electrode (BPE) focusing and surface acoustic wave (SAW) sorting modules. We successfully integrate four sequential microfluidic modules for multitarget separation within a single platform: (i) sorting particles and cells relying on the size and surface charge by adjusting the flow rate and electric field using a DLD array; (ii) alignment of cells or particles within a microfluidic channel by a bipolar electrode; (iii) separation of particles based on compressibility and density by the acoustic force; and (iv) separation of viable and nonviable cells using dielectric properties via the dielectrophoresis (DEP) force. As a proof of principle, we demonstrate the sorting of multiple cell and particle types (polystyrene (PS) particles, oil droplets, and viable and nonviable yeast cells) with high efficiency. This integrated microfluidic platform combines multiple functional components and, with its ability to noninvasively sort multiple targeted cells in a label-free manner relying on different properties, is compatible with high-definition imaging, showing great potential in diverse diagnostic and analysis applications.

Sheath-less focusing and sorting of cells or particles is an important preprocessing step in a variety of biochemical applications. Most of the previous sorting methods depend on the use of sheath flows to realize efficient cell focusing. The sheath flow dilutes the sample and requires precise flow control via additional channels. We, for the first time, reported a method of bipolar electrode (BPE)-based sheath-less focusing, switching, and tilted-angle standing surface acoustic wave-based sorting of cells and particles in continuous flow. The device consists of a piezoelectric substrate with a pair of BPEs for focusing and switching, and a pair of interdigitated transducers for cell sorting. Smaller cells experience a weak acoustic force and reach the lower outlet, whereas larger cells are subjected to a strong acoustic force such that they are propelled toward the upper outlet. We first validate the device functionality by sorting 5 and 8 μm PS beads with a high sorting efficiency. The working and deflection regions were increased by propelling the particle beam toward the bottom edge of BPE via changing the applied voltage of BPE, further improving the sorting performance with high efficiency (94%) and purity (92%). We then conducted a verification for sorting THP-1 and yeast cells, and the efficiency and purity reached 90.7 and 91.5%, respectively. This integrated device eliminates the requirement of balancing the flow of several sheath inlets and provides a robust and unique approach for cell sorting applications, showing immense promise in various applications, such as medical diagnosis, drug delivery, and personalized medicine.

Microfluidic systems have been developed widely in scaled-down processes of laboratory techniques, but they are usually limited in achieving stand-alone functionalities. It is highly desirable to exploit an integrated microfluidic device with multiple capabilities such as cell separation, single-cell trapping, and cell manipulation. Herein, we reported a microfluidic platform integrated with actuation electrodes, for separating cells and microbeads, and bipolar electrodes, for trapping, rotating, and propelling single cells and microbeads. The separation of cells and microbeads can be first achieved by deflective dielectrophoresis (DEP) barriers. Trapping experiments with yeast cells and polystyrene (PS) microbeads suspended in aqueous solutions with different conductivities were then conducted, showing that both cells and particles can be trapped at the center of wireless electrodes by negative DEP force. Upon application of a rotating electric field, yeast cells exhibit translational movement along the electrode edges, and self-rotation is seen at an array of bipolar electrodes when electrorotational torque and traveling wave DEP force are applied on the cells. The current approach allows us to switch the propulsion and rotation direction of cells by varying the frequency of the applied electric field. Beyond the achievements of single-cell manipulation, this system permits effective control of several particles or cells simultaneously. The integration of parallel sorting and single trapping stages within a microfluidic chip enables the prospect of high-throughput cell separation, single trapping, and large-scale cell locomotion and rotation in a noninvasive and disposable format, showing great potential in single-cell analysis, targeted drug delivery, and surgery.