CE09 - Nanomatériaux et nanotechnologies pour les produits du futur

Chemical Functionalization of Nanoporous Silicon for Sepsis Diagnosis – PORIDG

Submission summary

Sepsis, blood bacteremic infection, is one of the main mortality causes in the world. It is essential to treat sepsis as quickly as possible since the chances of survival decline by 7% each hour. As current sepsis diagnosis require several days, broad-range antibiotics are massively used in a first instance, driving the global antibiotic resistance threaten. Recently, 6 classes of blood metabolites have been identified as sepsis biomarkers. Metabolites being low molecular weight species present in trace in blood among abundant larger species, their detection and clinical use as biomarkers is a global failure. There is an urgent need for reliable and rapid metabolites separation strategies, from serum, compatible with classical Mass Spectrometry (MS) analysis for sepsis diagnosis. In 2014, the coordinator of PORIDG demonstrated a 15 minutes isolation technique of metabolites from serum compatible with MS. A drop of serum is spotted onto nanoporous silicon (pSi) leading to metabolite sterical trapping into the pores, while larger species are washed from the surface. Then, metabolites are directly analyzed by MALDI-MS. Statistical analysis of mass spectra discriminates highly pathological samples from normal samples (cardiovascular disease). Nevertheless discrimination of the intermediate disease stages is impossible and reflects a lack of sensitivity in disease-specific metabolites isolation and detection.

Based on these results, PORIDG aims at developing an innovative platform, based on pSi and MS, for highly sensitive sepsis diagnosis within 15 minutes. Two promising complementary novel strategies have been identified to solve the sensitivity problem: (i) develop pSi matrix that, in addition to sterical exclusion of larger species, enable isolation of sepsis-specific metabolites, among other metabolites, from serum. Herein we propose to monitor the pSi trapping capabilities by tuning its 3D surface chemistry. (ii) Optimize the pSi morphology to make it compatible with the highly sensitive DIOS-MS analysis technique.

In this framework, our sub-objectives are (i) identifying silane functionalization molecules that offer the highest binding affinity with each sepsis-specific metabolite. Optimal surface chemistry will be identified, or custom-designed, by combining innovative operando characterizations techniques (NAP-XPS, PM-IRRAS) of liquid / solid interfaces and state-of-the-art molecular dynamics simulations. (ii) Developing 3D-chemically-functionalized high aspect ratio pSi compatible with DIOS-MS analysis. A state-of-the-art solvent-free and high throughput process for pSi elaboration will be implemented. The relationship between pSi morphology and DIOS-MS efficiency will be investigated for the first time. A novel gas-phase functionalization process will be developed. Efficiency of functionalized pSi for sepsis metabolites capture will be evaluated on model solutions. (iii) Validating functionalized pSi and DIOS-MS as a platform for immediate sepsis diagnosis.

The final platform will be in the form of 6 chemically functionalized 5 x 5 mm pSi matrixes, compatible with serum spotting and DIOS-MS analysis. Each surface matrix will be functionalized independently and adapted to a targeted sepsis-specific metabolite. A standardized data statistical analysis method will be developed. The platform will be manufacturable at low-cost and high throughput for industrial transfer. A start-up has already shown great interest in PORIDG.

The goal of these disruptive strategies is to make a significant step toward sepsis diagnosis, but also in the field of characterizations and modeling of interfaces. To reach this objective, we will conduct an ambitious project that both rely on the coordinator’s expertise in pSi for metabolite capture, chemical vapor deposition processes, operando surface characterization and molecular dynamics simulations, as well as the expertise from the team in surface chemistry and nanofabrication processes.

Project coordination

Christelle YEROMONAHOS (Institut des Nanotechnologies de Lyon)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

INL Institut des Nanotechnologies de Lyon

Help of the ANR 255,240 euros
Beginning and duration of the scientific project: February 2019 - 42 Months

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