So far, nanostructuring of hard optical crystals has been exclusively limited to their surface, as stress-induced crack formation and propagation render high-precision volume processes ineffective(1,2). Here, we show that the rate of nanopore chemical etching in the popular laser crystals yttrium aluminium garnet and sapphire can be enhanced by more than five orders of magnitude (from <0.6 nm h(-1) to similar to 100 mu m h(-1)) by the use of direct laser writing, before etching. The process makes it possible to produce arbitrary three-dimensional nanostructures with 100 nm feature sizes inside centimetre-scale laser crystals without brittle fracture. To showcase the potential of the technique we fabricate subwavelength diffraction gratings and nanostructured optical waveguides in yttrium aluminium garnet and millimetre-long nanopores in sapphire. The approach offers a pathway for transferring concepts from nanophotonics to the fields of solid-state lasers and crystal optics.

Inertial microfluidic particles sorting represents a critical task in many areas of biology, biotechnology, and medicine, including the isolation from blood of rare target cell populations, like e.g. circulating tumor cells (CTCs) and circulating fetal cells (CFCs).

In biology and medicine, the application of microfluidics filtration technologies to the separation of rare particles requires processing large amounts of liquid in a short time to achieve an effective separation yield. In this direction, the parallelization of the sorting process is desirable, but not so easy to implement in a lab on a chip (LoC) device, especially if it is fully inertial. In this work, we report on femtosecond laser microfabrication (FLM) of a poly(methyl methacrylate) (PMMA) inertial microfluidic sorter, separating particles based on their size and providing an enhanced-throughput capability. The LoC device consists of a microchannel with expansion chambers provided with siphoning outlets, for a continuous sorting process. Different from soft lithography, which is the most used technique for LoC prototyping, FLM allows developing 3D microfluidic networks connecting both sides of the chip. Exploiting this capability, we are able to parallelize the circuit while keeping a single output for the sorted particles and one for the remaining sample, thus increasing the number of processed particles per unit time without compromising the simplicity of the chip connections. We investigated several device layouts (at different flow rates) to define a configuration that maximizes the selectivity and the throughput.

Since the pioneering work of Ashkin and coworkers, back in 1970, optical manipulation gained an increasing interest among the scientific community. Indeed, the advantages and the possibilities of this technique are unsubtle, allowing for the manipulation of small particles with a broad spectrum of dimensions (nanometers to micrometers size), with no physical contact and without affecting the sample viability. Thus, optical manipulation rapidly found a large set of applications in different fields, such as cell biology, biophysics, and genetics. Moreover, large benefits followed the combination of optical manipulation and microfluidic channels, adding to optical manipulation the advantages of microfluidics, such as a continuous sample replacement and therefore high throughput and automatic sample processing. In this work, we will discuss the state of the art of these optofluidic devices, where optical manipulation is used in combination with microfluidic devices. We will distinguish on the optical method implemented and three main categories will be presented and explored: (i) a single highly focused beam used to manipulate the sample, (ii) one or more diverging beams imping on the sample, or (iii) evanescent wave based manipulation.

Vortex-aided particle separation is a powerful method to efficiently isolate circulating tumor cells from blood, since it allows high throughput and continuous sample separation, with no need for time-consuming sample preprocessing. With this approach, only the larger particles from a heterogeneous sample will be stably trapped in reservoirs that expand from a straight microfluidic channel, allowing for efficient particle sorting along with simultaneous concentration. A possible limitation is related to the loss of particles from vortex traps due to particle-particle interactions that limit the final cellularity of the enriched solution. It is fundamental to minimize this issue considering that a scant number of target cells are diluted in highly cellular blood. In this work, we present a device for size-based particle separation, which exploits the well-consolidated vortex-aided sorting, but new reservoir layouts are presented and investigated in order to increase the trapping efficiency of the chip. Through simulations and experimental validations, we have been able to optimize the device design to increase the maximum number of particles that can be stably trapped in each reservoir and therefore the total efficiency of the chip.

Microfluidic lenses are relevant optical components for sensing application in lab-on-a-chip devices, guaranteeing a robust alignment of the elements, a high level of compactness and tunable optical properties. In this work we describe an innovative integrated in-plane microfluidic lens. The device shows both an optimized shape capable of reducing spherical aberrations and periodically tunable optical properties. Indeed through the combination of the lens with a droplet generator module, we have been able to obtain an integrated optofluidic modulator capable of both on-demand on/off switching and periodic modulation of light. The device possesses a simple 3D geometry, which has been realized by exploiting the 3D capability of the femtosecond laser micromachining fabrication technique.

The application of fully-inertial size-based microfluidic filtration technologies for particle separation is an attractive tool, which not only offers label-free control of the microenvironment during separation, but also facilitates integration and automation for high throughput sample processing. In this work, we exploit 3D computational fluid dynamics (CFD) simulations based on the lattice Boltzmann method to evaluate the performance of a microfluidic device specifically designed to trap and extract particles by inertial focusing and microscale vortices. The device geometry consists of a straight microchannel, followed downstream by a microchamber with outlets for continuous size-based separation. Simulations were carried out to characterize the flow properties of the microfluidic device. Here, the influence of the Reynolds number (Re), the chamber dimensions and the outlet channels aspect ratio on the streamtracer distribution were studied. In order to support the simulation results, some preliminary experimental validations have been conducted, finding that the model can accurately characterize the flow in the studied geometry. The results of the simulations and experiments presented in this paper can be very useful to support the design of continuous-flow particle sorting lab-on-a-chip (LOC) devices.