No abstract

A novel inertial focusing platform creates a single-stream microparticle train in a single-focal plane without sheath fluids and external forces, all in a high-throughput manner. The proposed design consists of a low-aspect-ratio straight channel interspersed with a series of constrictions in height arranged orthogonally, making use of inertial focusing and geometry-induced secondary flows. Focusing efficiency as high as 99.77% is demonstrated with throughput as high as 36 000 particles s(-1) for a variety of different sized particles and cells.

In this paper, we review the state-of-the-art in surface-enhanced Raman scattering (SERS) based optical detection techniques with an application focus on cancer diagnostics. As we describe herein, SERS has several analytical, biological and engineering advantages over other methods including extremely high sensitivity, inherent molecular specificity of unlabeled targets, and narrow spectral bands. We review advances in both in vitro and in vivo applications of SERS and examine how technical issues with the technology are being addressed. A special technology focus is given to emerging optofluidic devices which aim to merge microfluidic and optical detection technologies into simple packages. We conclude with a brief discussion of some of the emerging challenges in the field and some of the approaches that are likely to enhance their application.

We present a hydrodynamic cell deformation-induced intracellular delivery platform, termed “hydroporator”.

Complex three-dimensional (3D)-shaped particles could play unique roles in biotechnology, structural mechanics and self-assembly. Current methods of fabricating 3D-shaped particles such as 3D printing, injection moulding or photolithography are limited because of low-resolution, low-throughput or complicated/expensive procedures. Here, we present a novel method called optofluidic fabrication for the generation of complex 3D-shaped polymer particles based on two coupled processes: inertial flow shaping and ultraviolet (UV) light polymerization. Pillars within fluidic platforms are used to deterministically deform photosensitive precursor fluid streams. The channels are then illuminated with patterned UV light to polymerize the photosensitive fluid, creating particles with multi-scale 3D geometries. The fundamental advantages of optofluidic fabrication include high-resolution, multi-scalability, dynamic tunability, simple operation and great potential for bulk fabrication with full automation. Through different combinations of pillar configurations, flow rates and UV light patterns, an infinite set of 3D-shaped particles is available, and a variety are demonstrated.

Fluid inertia which has conventionally been neglected in microfluidics has been gaining much attention for particle and cell manipulation because inertia-based methods inherently provide simple, passive, precise and high-throughput characteristics. Particularly, the inertial approach has been applied to blood separation for various biomedical research studies mainly using spiral microchannels. For higher throughput, parallelization is essential; however, it is difficult to realize using spiral channels because of their large two dimensional layouts. In this work, we present a novel inertial platform for continuous sheathless particle and blood cell separation in straight microchannels containing microstructures. Microstructures within straight channels exert secondary flows to manipulate particle positions similar to Dean flow in curved channels but with higher controllability. Through a balance between inertial lift force and microstructure-induced secondary flow, we deterministically position microspheres and cells based on their sizes to be separated downstream. Using our inertial platform, we successfully sorted microparticles and fractionized blood cells with high separation efficiencies, high purities and high throughputs. The inertial separation platform developed here can be operated to process diluted blood with a throughput of 10.8 mL min(-1)via radially arrayed single channels with one inlet and two rings of outlets.

Fluid inertia has been used to position microparticles in confined channels because it leads to precise and predictable particle migration across streamlines in a high-throughput manner. To focus particles, typically two inertial effects have been employed: inertial migration of particles in combination with geometry-induced secondary flows. Still, the strong scaling of inertial effects with fluid velocity or channel flow rate have made it challenging to design inertial focusing systems for single-stream focusing using large-scale microchannels. Use of large-scale microchannels (≥100 μm) reduces clogging over long durations and could be suitable for non-single-use flow cells in cytometry systems. Here, we show that microstructure-induced helical vortices yield single-stream focusing of microparticles with continuous and robust operation. Numerical and experimental results demonstrate how structures contribute to improve focusing in these larger channels, through controllable cross-stream particle migration, aided by locally-tuned secondary flows from sequential obstacles that act to bring particles closer to a single focusing equilibrium position. The large-scale inertial focuser developed here can be operated in a high-throughput manner with a maximum throughput of approximately 13,000 particles per s.

The introduction of nanomaterials into cells is an indispensable process for studies ranging from basic biology to clinical applications. To deliver foreign nanomaterials into living cells, traditionally endocytosis, viral and lipid nanocarriers or electroporation are mainly employed; however, they critically suffer from toxicity, inconsistent delivery, and low throughput and are time-consuming and labor-intensive processes. Here, we present a novel inertial microfluidic cell hydroporator capable of delivering a wide range of nanomaterials to various cell types in a single-step without the aid of carriers or external apparatus. The platform inertially focuses cells into the channel center and guides cells to collide at a T-junction. Controlled compression and shear forces generate transient membrane discontinuities that facilitate passive diffusion of external nanomaterials into the cell cytoplasm while maintaining high cell viability. This hydroporation method shows superior delivery efficiency, is high-throughput, and has high controllability; moreover, its extremely simple and low-cost operation provides a powerful and practical strategy in the applications of cellular imaging, biomanufacturing, cell-based therapies, regenerative medicine, and disease diagnosis.