Carretero, A. | Search bioRxiv

bioRxiv2024

Wafer-scale integration of alpha-quartz thin films towards super high frequency piezoelectric bioNEMS for arbovirus detection

Micro and nanoelectromechanical systems (MEMS/NEMS), especially piezoelectric resonators, offer a promising strategy for the manufacturing of point-of-care devices providing rapid, sensitive, and field-deployable tests with minimal user training for the diagnostic of viral infections. High-frequency (HF) MEMS/NEMS have the potential for ultrasensible mass-loading devices. Yet, their use for biomedical applications requires challenging manufacturing qualities. Here, we develop a large-scale chemical integration of epitaxial -quartz (100) thin films on silicon wafers up to 4-inches. This methodology allows the microfabrication of wafer-scale piezoelectric -quartz/silicon bioMEMS using a recognition layer capable of selectively detecting emerging arboviruses over other viral loads. Using contact-free vibrometry, we show a mass sensitivity of the bioMEMS device of 22.4 pg/Hz in liquid conditions and a Chikungunya virus limit of detection of 9 ng/ml. To reach piezoelectric transduction for compact quartz sensor devices, we develop NEMS resonators at super HF, i.e., 17.8 GHz with a quality factor of 280 which represents a QxF product of 4.98{middle dot}1012. These -quartz NEMS can reach thicknesses between 100 and 800 nm and lateral dimensions up to 9 mm2. Our work opens the door for cost-efficient single-chip epitaxial piezoelectric -quartz/Si ultrasensitive NEMS sensors manufactured exclusively by soft-chemistry for biomedical applications and many other fields.

bioengineering↗

bioRxiv2024

A bottom-up approach identifies the antipsychotic and antineoplastic trifluoperazine and the ribose derivative deoxytubercidin as novel microglial phagocytosis inhibitors.

Phagocytosis is an indispensable function of microglia, the brain professional phagocytes. Microglia are particularly efficient phagocytosing cells that undergo programmed cell death (apoptosis) in physiological conditions. However, mounting evidence suggests microglial phagocytosis dysfunction in multiple brain disorders. These observations prompted us to search for phagocytosis modulators (enhancers or inhibitors) with therapeutic potential. We used a bottom-up strategy that consisted on the identification of phagocytosis modulators using phenotypic high throughput screenings (HTSs) in cell culture and validation in organotypic cultures and in vivo. We performed two complementary HTS campagnes: at Achucarro, we used primary cultures of mouse microglia and compounds of the Prestwick Chemical Library; at Roche, we used human iPSC derived macrophage-like cells and a proprietary chemo-genomic library with 2,200 compounds with known mechanism-of-action. Next, we validated the more robust compounds using hippocampal organotypic cultures and identified two hits: trifluoperazine, a dopaminergic and adrenergic antagonist used as an antipsychotic and antineoplastic; and deoxytubercidin, a ribose derivative. Finally, we tested whether these compounds were able to modulate phagocytosis of apoptotic newborn cells in the adult hippocampal neurogenic niche in vivo by administering them into the mouse hippocampus using osmotic minipumps. We confirmed that both trifluoperazine and deoxytubercidin have anti-phagocytic activity in vivo, and validated our bottom-up strategy to identify novel phagocytosis modulators. These results show that chemical libraries with anotated mechanism of action are an starting point for the pharmacological modulation of microglia in drug discovery projects aiming at the therapeutic manipulation of phagocytosis in brain diseases. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC="FIGDIR/small/599284v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@13ed994org.highwire.dtl.DTLVardef@13ea710org.highwire.dtl.DTLVardef@4a1c7dorg.highwire.dtl.DTLVardef@1945f00_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗