Publications by authors named "Matteo Agostini"

10 Publications

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Acoustic streaming of microparticles using graphene-based interdigital transducers.

Nanotechnology 2021 May 24. Epub 2021 May 24.

Center for Nanotechnology Innovation, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56125 Pisa, Pisa, 56125, ITALY.

Surface acoustic wave (SAW) devices offer many benefits in chemistry and biomedicine, enabling precise manipulation of micro-droplets, mixing of liquids by acoustic streaming and pumping of liquids in enclosed channels, while presenting a cost-effective and easy fabrication and integration with electronic devices. In this work, we present microfluidic devices which use graphene-based interdigital transducers (IDTs) to generate SAWs with a frequency of 100 MHz and an amplitude of up to 200 pm, which allow us to manipulate microparticle solutions by acoustic streaming. Due to the negligible mass loading of the piezoelectric surface by graphene, the SAWs generated by these devices have no frequency shift, typically observed when metal IDTs are used.
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http://dx.doi.org/10.1088/1361-6528/ac0473DOI Listing
May 2021

Ultra-high-frequency (UHF) surface-acoustic-wave (SAW) microfluidics and biosensors.

Nanotechnology 2021 May 10;32(31). Epub 2021 May 10.

INTA srl, Intelligent Acoustics Systems, Via Nino Pisano 14, I-56122 Pisa, Italy.

Surface acoustic waves (SAWs) have the potential to become the basis for a wide gamut of lab-on-a-chips (LoCs). These mechanical waves are among the most promising physics that can be exploited for fulfilling all the requirements of commercially appealing devices that aim to replace-or help-laboratory facilities. These requirements are low processing cost of the devices, scalable production, controllable physics, large flexibility of tasks to perform, easy device miniaturization. To date, SAWs are among the small set of technologies able to both manipulate and analyze biological liquids with high performance. Therefore, they address the main needs of microfluidics and biosensing. To this purpose, the use of high-frequency SAWs is key. In the ultra-high-frequency regime (UHF, 300 MHz-3 GHz) SAWs exhibit large sensitivities to molecule adsorption and unparalleled fluid manipulation capabilities, together with overall device miniaturization. The UHF-SAW technology is expected to be the realm for the development of complex, reliable, fully automated, high-performance LoCs. In this review, we present the most recent works on UHF-SAWs for microfluidics and biosensing, with a particular focus on the LoC application. We derive the relevant scale laws, useful formulas, fabrication guidelines, current limitations of the technology, and future developments.
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http://dx.doi.org/10.1088/1361-6528/abfabaDOI Listing
May 2021

Dysregulated miRNAs in bone cells of patients with Gorham-Stout disease.

FASEB J 2021 Mar;35(3):e21424

Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Gorham-Stout disease (GSD) is a very rare disease characterized by increased bone erosion with angiomatous proliferation. The mechanisms underlying this disorder have not been deeply investigated. Due to its rarity, no guidelines are currently available for treatment and management of GSD. We recently evaluated the cellular alterations of the bone remodeling in patients showing that osteoclast precursors displayed increased ability to differentiate into osteoclasts and that affected osteoclasts resorb bone more actively than control cells. Moreover, osteoblasts isolated from a patient showed a defective ability to form mineralized nodules. In this paper, we investigated the molecular pathways involved in the cellular defects of GSD bone cells. For this study, we recruited nine patients and performed miRNome analysis of bone cells. Between the 178 miRNAs robustly expressed in GSD osteoclasts, significant modulation of three miRNAs (miR-1246, miR-1-3p, and miR-137-3p) involved in the regulation of osteoclast formation and activity or in the angiomatous proliferation was found in patients' cells. Interestingly, miR-1246 was also up-regulated in serum exosomes from patients. Analysis of miRNAs from patient osteoblasts suggested alteration of miR-204a-5p, miR-615-3p and miR-378a-3p regulating osteoblast function and differentiation. The resulting miRNA pattern may help to understand better the mechanisms involved in GSD and to identify new potential therapeutic targets for this rare disease.
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http://dx.doi.org/10.1096/fj.202001904RRDOI Listing
March 2021

Atomistic simulations of gold surface functionalization for nanoscale biosensors applications.

Nanotechnology 2021 Feb;32(9):095702

Dipartimento di Scienze Chimiche, Università di Padova, I-35131 Padova, Italy. Istituto Nanoscienze-CNR-NANO, Center S3, via G. Campi 213/A, I-41125 Modena, Italy.

A wide class of biosensors can be built via functionalization of gold surface with proper bio conjugation element capable of interacting with the analyte in solution, and the detection can be performed either optically, mechanically or electrically. Any change in physico-chemical environment or any slight variation in mass localization near the surface of the sensor can cause differences in nature of the transduction mechanism. The optimization of such sensors may require multiple experiments to determine suitable experimental conditions for the immobilization and detection of the analyte. Here, we employ molecular modeling techniques to assist the optimization of a gold-surface biosensor. The gold surface of a quartz-crystal-microbalance sensor is functionalized using polymeric chains of poly(ethylene glycol) (PEG) of 2 KDa molecular weight, which is an inert long chain amphiphilic molecule, supporting biotin molecules (bPEG) as the ligand molecules for streptavidin analyte. The PEG linkers are immobilized onto the gold surface through sulphur chemistry. Four gold surfaces with different PEG linker density and different biotinylation ratio between bPEG and PEG, are investigated by means of state-of-the art atomistic simulations and compared with available experimental data. Results suggest that the amount of biotin molecules accessible for the binding with the protein increases upon increasing the linkers density. At the high density a 1:1 ratio of bPEG/PEG can further improve the accessibility of the biotin ligand due to a strong repulsion between linker chains and different degree of hydrophobicity between bPEG and PEG linkers. The study provides a computaional protocol to model sensors at the level of single molecular interactions, and for optimizing the physical properties of surface conjugated ligand which is crucial to enhance output of the sensor.
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http://dx.doi.org/10.1088/1361-6528/abc6dcDOI Listing
February 2021

Dissecting the mechanisms of bone loss in Gorham-Stout disease.

Bone 2020 01 13;130:115068. Epub 2019 Sep 13.

Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, Rome, Italy. Electronic address:

Gorham-Stout disease (GSD) is a rare disorder characterized by progressive osteolysis and angiomatous proliferation. Since the mechanisms leading to bone loss in GSD are not completely understood, we performed histological, serum, cellular and molecular analyses of 7 patients. Increased vessels, osteoclast number and osteocyte lacunar area were revealed in patients' bone biopsies. Biochemical analysis of sera showed high levels of ICTP, Sclerostin, VEGF-A and IL-6. In vitro experiments revealed increased osteoclast differentiation and activity, and impaired mineralization ability of osteoblasts. To evaluate the involvement of systemic factors in GSD, control cells were treated with patients' sera and displayed an increase of osteoclastogenesis, bone resorption activity and a reduction of osteoblast function. Interestingly, GSD sera stimulated the vessel formation by endothelial cells EA.hy926. These results suggest that bone cell autonomous alterations with the cooperation of systemic factors are involved in massive bone loss and angiomatous proliferation observed in GSD patients.
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http://dx.doi.org/10.1016/j.bone.2019.115068DOI Listing
January 2020

Intrinsic Bone Defects in Cystinotic Mice.

Am J Pathol 2019 05 19;189(5):1053-1064. Epub 2019 Feb 19.

Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, Rome, Italy.

Cystinosis is a rare lysosomal storage disorder caused by loss-of-function mutations of the CTNS gene, encoding cystinosin, a symporter that mediates cystine efflux from lysosomes. Approximately 95% of patients with cystinosis display renal Fanconi syndrome, short stature, osteopenia, and rickets. In this study, we investigated whether the absence of cystinosin primarily affects bone remodeling activity, apart from the influences of the Fanconi syndrome on bone mineral metabolism. Using micro-computed tomography and histomorphometric and bone serum biomarker analysis, we evaluated the bone phenotype of 1-month-old Ctns knockout (KO) male mice without tubulopathy. An in vitro study was performed to characterize the effects of cystinosin deficiency on osteoblasts and osteoclasts. Micro-computed tomography analysis showed a reduction of trabecular bone volume, bone mineral density, and number and thickness in KO mice compared with wild-type animals; histomorphometric analysis revealed a reduction of osteoblast and osteoclast parameters in tibiae of cystinotic mice. Decreased levels of serum procollagen type 1 amino-terminal propeptide and tartrate-resistant acid phosphatase in KO mice confirmed reduced bone remodeling activity. In vitro experiments showed an impairment of Ctns osteoblasts and osteoclasts. In conclusion, cystinosin deficiency primarily affects bone cells, leading to a bone loss phenotype of KO mice, independent from renal failure.
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http://dx.doi.org/10.1016/j.ajpath.2019.01.015DOI Listing
May 2019

Surface-Acoustic-Wave (SAW)-Driven Device for Dynamic Cell Cultures.

Anal Chem 2018 06 1;90(12):7450-7457. Epub 2018 Jun 1.

NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore , Piazza San Silvestro 12 , 56127 Pisa , Italy.

In the last few decades, new types of cell cultures have been introduced to provide better cell survival and development, with micro- and nanoenvironmental physicochemical conditions aimed at mimicking those present in vivo. However, despite the efforts made, the systems available to date are often difficult to replicate and use. Here, an easy-to-use surface-acoustic-wave (SAW)-based platform is presented for realizing dynamic cell cultures that is compatible with standard optical microscopes, incubators, and cell-culture dishes. The SAW chip is coupled to a standard Petri dish via a polydimethylsiloxane (PDMS) disc and consists of a lithium niobate (LN) substrate on which gold interdigital transducers (IDTs) are patterned to generate the SAWs and induce acoustic streaming in the dish. SAW excitation is verified and characterized by laser Doppler vibrometry, and the fluid dynamics is studied by microparticle image velocimetry (μPIV). Heating is measured by an infrared (IR) thermal camera. We finally tested this device with the U-937 monocyte cell line for viability and proliferation and cell-morphological analysis. The data demonstrate that it is possible to induce significant fluid recirculation within the Petri dish while maintaining negligible heating. Remarkably, cell proliferation in this condition was enhanced by 36 ± 12% with respect to those of standard static cultures. Finally, we show that cell death does not increase and that cell morphology is not altered in the presence of SAWs. This device is the first demonstration that SAW-induced streaming can mechanically improve cell proliferation and further supports the great versatility and biocompatibility of the SAW technology for cell manipulation.
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http://dx.doi.org/10.1021/acs.analchem.8b00972DOI Listing
June 2018

The Role of Extracellular Vesicles in Bone Metastasis.

Int J Mol Sci 2018 Apr 10;19(4). Epub 2018 Apr 10.

Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, 00165 Rome, Italy.

Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV) in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed, it was shown that extracellular vesicles, including exosomes and microvesicles, released from tumor cells can modify the bone microenvironment, allowing the formation of osteolytic, osteosclerotic, and mixed mestastases. In turn, bone-derived EV can stimulate the proliferation of tumor cells. The inhibition of EV-mediated crosstalk between cancer and bone cells could represent a new therapeutic target for bone metastasis.
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http://dx.doi.org/10.3390/ijms19041136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979436PMC
April 2018

Surface Acoustic Wave (SAW)-Enhanced Chemical Functionalization of Gold Films.

Sensors (Basel) 2017 Oct 26;17(11). Epub 2017 Oct 26.

National Enterprise for nanoScience and nanoTechnology (NEST), Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy.

Surface chemical and biochemical functionalization is a fundamental process that is widely applied in many fields to add new functions, features, or capabilities to a material's surface. Here, we demonstrate that surface acoustic waves (SAWs) can enhance the chemical functionalization of gold films. This is shown by using an integrated biochip composed by a microfluidic channel coupled to a surface plasmon resonance (SPR) readout system and by monitoring the adhesion of biotin-thiol on the gold SPR areas in different conditions. In the case of SAW-induced streaming, the functionalization efficiency is improved ≈ 5 times with respect to the case without SAWs. The technology here proposed can be easily applied to a wide variety of biological systems (e.g., proteins, nucleic acids) and devices (e.g., sensors, devices for cell cultures).
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http://dx.doi.org/10.3390/s17112452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713185PMC
October 2017

A surface-acoustic-wave-based cantilever bio-sensor.

Biosens Bioelectron 2015 Jun 30;68:570-576. Epub 2014 Dec 30.

Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, I-56127 Pisa, Italy.

A scalable surface-acoustic-wave- (SAW-) based cantilevered device for portable bio-chemical sensing applications is presented. Even in the current, proof-of-principle implementation this architecture is shown to outperform commercial quartz-crystal microbalances in terms of sensitivity. Adhesion of analytes on a functionalized surface of the cantilever shifts the resonant frequency of a SAW-generating transducer due to the stress-induced variation of the speed of surface acoustic modes. We discuss the relevance of this approach for diagnostics applications based on miniaturized devices.
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http://dx.doi.org/10.1016/j.bios.2014.12.058DOI Listing
June 2015