Beyond liquid biopsy: Toward non-invasive assays for distanced cancer diagnostics in pandemics.

Liquid biopsy technologies have seen a significant improvement in the last decade, offering the possibility of reliable analysis and diagnosis from several biological fluids. The use of these technologies can overcome the limits of standard clinical methods, related to invasiveness and poor patient compliance. Along with this there are now mature examples of lab-on-chips (LOC) which are available and could be an emerging and breakthrough technology for the present and near-future clinical demands that provide sample treatment, reagent addition and analysis in a sample-in/answer-out approach. The possibility of combining non-invasive liquid biopsy and LOC technologies could greatly assist in the current need for minimizing exposure and transmission risks. The recent and ongoing pandemic outbreak of SARS-CoV-2, indeed, has heavily influenced all aspects of life worldwide. Ordinary tasks have been forced to switch from "in presence" to "distanced", limiting the possibilities for a large number of activities in all fields of life outside of the home. Unfortunately, one of the settings in which physical distancing has assumed noteworthy consequences is the screening, diagnosis and follow-up of diseases. In this review, we analyse biological fluids that are easily collected without the intervention of specialized personnel and the possibility that they may be used -or not-for innovative diagnostic assays. We consider their advantages and limitations, mainly due to stability and storage and their integration into Point-of-Care diagnostics, demonstrating that technologies in some cases are mature enough to meet current clinical needs.

SMILE Platform: An Innovative Microfluidic Approach for On-Chip Sample Manipulation and Analysis in Oral Cancer Diagnosis.

Oral cancer belongs to the group of head and neck cancers, and, despite its large diffusion, it suffers from low consideration in terms of prevention and early diagnosis. The main objective of the SMILE platform is the development of a low-cost device for oral cancer early screening with features of high sensitivity, specificity, and ease of use, with the aim of reaching a large audience of possible users and realizing real prevention of the disease. To achieve this goal, we realized two microfluidic devices exploiting low-cost materials and processes. They can be used in combination or alone to obtain on-chip sample preparation and/or detection of circulating tumor cells, selected as biomarkers of oral cancer. The realized devices are completely transparent with plug-and-play features, obtained thanks to a highly customized architecture which enables users to easily use them, with potential for a common use among physicians or dentists with minimal training.

Innovative 3D Microfluidic Tools for On-Chip Fluids and Particles Manipulation: From Design to Experimental Validation.

Micromixers are essential components in lab-on-a-chip devices, of which the low efficiency can limit many bio-application studies. Effective mixing with automation capabilities is still a crucial requirement. In this paper, we present a method to fabricate a three-dimensional (3D) poly(methyl methacrylate) (PMMA) fluidic mixer by combining computer-aided design (CAD), micromilling technology, and experimental application via manipulating fluids and nanoparticles. The entire platform consists of three microfabricated layers with a bottom reservoir-shaped microchannel, a central serpentine channel, and a through-hole for interconnection and an upper layer containing inlets and outlet. The sealing process of the three layers and the high-precision and customizable methods used for fabrication ensure the realization of the monolithic 3D architecture. This provides buried running channels able to perform passive chaotic mixing and dilution functions, thanks to a portion of the pathway in common between the reservoir and serpentine layers. The possibility to plug-and-play micropumping systems allows us to easily demonstrate the feasibility and working features of our device for tracking the mixing and dilution performances of the micromixer by using colored fluids and fluorescent nanoparticles as the proof of concept. Exploiting the good transparency of the PMMA, spatial liquid composition and better control over reaction variables are possible, and the real-time monitoring of experiments under a fluorescence microscope is also allowed. The tools shown in this paper are easily integrable in more complex lab-on-chip platforms.