3D rotation is one of many fundamental manipulations to cells and imperative in a wide range of applications in single cell analysis involving biology, chemistry, physics and medicine. In this article, we report a dielectrophoresis-based, on-chip manipulation method that can load and rotate a single cell for 3D cell imaging and multiple biophysical property measurements. To achieve this, we trapped a single cell in constriction and subsequently released it to a rotation chamber formed by four sidewall electrodes and one transparent bottom electrode. In the rotation chamber, rotating electric fields were generated by applying appropriate AC signals to the electrodes for driving the single cell to rotate in 3D under control. The rotation spectrum for in-plane rotation was used to extract the cellular dielectric properties based on a spherical single-shell model, and the stacked images of out-of-plane cell rotation were used to reconstruct the 3D cell morphology to determine its geometric parameters. We have tested the capabilities of our method by rotating four representative mammalian cells including HeLa, C3H10, B lymphocyte, and HepaRG. Using our device, we quantified the area-specific membrane capacitance and cytoplasm conductivity for the four cells, and revealed the subtle difference of geometric parameters (i.e., surface area, volume, and roughness) by 3D cell imaging of cancer cells and normal leukocytes. Combining microfluidics, dielectrophoresis, and microscopic imaging techniques, our electrorotation-on-chip (EOC) technique is a versatile method for manipulating single cells under investigation and measuring their multiple biophysical properties.

Single cell trapping increasingly serves as a key manipulation technique in single cell analysis for many cutting-edge cell studies. Due to their inherent advantages, microfluidic devices have been widely used to enable single cell immobilization. To further improve the single cell trapping efficiency, this paper reports on a passive hydrodynamic microfluidic device based on the “least flow resistance path” principle with geometry optimized in line with corresponding cell types. Different from serpentine structure, the core trapping structure of the micro-device consists of a series of concatenated T and inverse T junction pairs which function as bypassing channels and trapping constrictions. This new device enhances the single cell trapping efficiency from three aspects: (1) there is no need to deploy very long or complicated channels to adjust flow resistance, thus saving space for each trapping unit; (2) the trapping works in a “deterministic” manner, thus saving a great deal of cell samples; and (3) the compact configuration allows shorter flowing path of cells in multiple channels, thus increasing the speed and throughput of cell trapping. The mathematical model of the design was proposed and optimization of associated key geometric parameters was conducted based on computational fluid dynamics (CFD) simulation. As a proof demonstration, two types of PDMS microfluidic devices were fabricated to trap HeLa and HEK-293T cells with relatively significant differences in cell sizes. Experimental results showed 100% cell trapping and 90% single cell trapping over 4 × 100 trap sites for these two cell types, respectively. The space saving is estimated to be 2-fold and the cell trapping speed enhancement to be 3-fold compared to previously reported devices. This device can be used for trapping various types of cells and expanded to trap cells in the order of tens of thousands on 1-cm² scale area, as a promising tool to pattern large-scale single cells on specific substrates and facilitate on-chip cellular assay at the single cell level.

Conventional imaging systems can only capture light intensity. Meanwhile, the lost phase information may be critical for a variety of applications such as label-free microscopy and optical metrology. Existing phase retrieval techniques typically require a bulky setup, multiframe measurements, or prior information of the target scene. Here, we proposed an extremely compact system for complex amplitude imaging, leveraging the extreme versatility of a single-layer metalens to generate spatially multiplexed and polarization phase–shifted point spread functions. Combining the metalens with a polarization camera, the system can simultaneously record four polarization shearing interference patterns along both in-plane directions, thus allowing the deterministic reconstruction of the complex amplitude light field in a single shot. Using an incoherent light-emitting diode as the illumination, we experimentally demonstrated speckle-noise–free complex amplitude imaging for both static and moving objects with tailored magnification ratio and field of view. The miniaturized and robust system may open the door for complex amplitude imaging in portable devices for point-of-care applications.

The precise rotation of suspended cells is one of the many fundamental manipulations used in a wide range of biotechnological applications such as cell injection and enucleation in nuclear transfer (NT) cloning. Noticeably scarce among the existing rotation techniques is the three-dimensional (3D) rotation of cells on a single chip. Here we present an alternating current (ac) induced electric field-based biochip platform, which has an open-top sub-mm square chamber enclosed by four sidewall electrodes and two bottom electrodes, to achieve rotation about the two axes, thus 3D cell rotation. By applying an ac potential to the four sidewall electrodes, an in-plane (yaw) rotating electric field is generated and in-plane rotation is achieved. Similarly, by applying an ac potential to two opposite sidewall electrodes and the two bottom electrodes, an out-of-plane (pitch) rotating electric field is generated and rolling rotation is achieved. As a prompt proof-of-concept, bottom electrodes were constructed with transparent indium tin oxide (ITO) using the standard lift-off process and the sidewall electrodes were constructed using a low-cost micro-milling process and then assembled to form the chip. Through experiments, we demonstrate rotation of bovine oocytes of ~120 μm diameter about two axes, with the capability of controlling the rotation direction and the rate for each axis through control of the ac potential amplitude, frequency, and phase shift, and cell medium conductivity. The maximum observed rotation rate reached nearly 140° s⁻¹, while a consistent rotation rate reached up to 40° s⁻¹. Rotation rate spectra for zona pellucida-intact and zona pellucida-free oocytes were further compared and found to have no effective difference. This simple, transparent, cheap-to-manufacture, and open-top platform allows additional functional modules to be integrated to become a more powerful cell manipulation system.