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EmbryoSpin: Nuclear magnetic resonance at the scale of a single embryo

English title EmbryoSpin: Nuclear magnetic resonance at the scale of a single embryo
Applicant Grisi Marco
Number 180268
Funding scheme Bridge - Proof of Concept
Research institution
Institution of higher education EPF Lausanne - EPFL
Main discipline Microelectronics. Optoelectronics
Start/End 01.03.2018 - 31.07.2019
Approved amount 194'400.00
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All Disciplines (3)

Discipline
Microelectronics. Optoelectronics
Embryology, Developmental Biology
Biochemistry

Keywords (9)

NMR; single-embryo; sub-nL; CMOS; IVF; human embryo; nuclear magnetic resonance; embryo; in vitro fertilization

Lay Summary (Italian)

Lead
La risonanza magnetica nucleare è una tecnica spettroscopica che permette di avere accesso ad informazioni sulla chimica nella materia. Nota per essere bio-compatibile e di natura non invasiva, la risonanza magnetica è oggi uno strumento essenziale per la medicina diagnostica. L'uso della risonanza magnetica sulla scala di organismi multicellulari complessi, come l'uomo e il topo, è già abilitato e ottimizzato grazie alla strumentazione in commercio. Tuttavia, l'uso di questa tecnica alla scala tipica di microorganismi e cellule è al momento ostacolato dalle limitazioni tecniche della strumentazione convenzionale.
Lay summary
Soggetto e obbiettivo 

In questo progetto si vogliono implementare prototipi di sensori concepiti per abilitare l'uso della risonanza magnetica alla scala di un embrione umano. Tale tecnologia offrirà sensitività migliorate alla scala microscopica combinate con un grado di versatilità eccezionale. L'uso di questa tecnologia permetterà, per la prima volta, l'uso della risonanza magnetica su singoli embrioni di mammifero, micro-tessuti derivati da cellule staminali, o ancora organismi unicellulari. Lo sviluppo tecnico del prototipo si concentra su aspetti chiave come la facilità di uso e la compatibilità con i campi magnetici tipicamente usati nei laboratori di tutto il mondo. Un prototipo con queste caratteristiche mi permetterà di fare studi di fattibilità su embrioni di bovino e materiale derivato da cellule staminali. I dati saranno il nostro "Proof of Concept", che verrà poi possibilmente impugnato per cercare un accordo con una clinica IVF e muovere i primi passi verso degli studi preclinici atti a validare l'uso della risonanza magnetica anche nel campo della fertilizzazione in vitro.

Contesto socio-scientifico

Oltre all'evidente interesse scientifico, si prevede l'uso di queste tecnologie anche in campi medici che aprirebbero a mercati consistenti. Un campo clinico che guida un grosso mercato è quello del trattamento della infertilità, dove micro-sensori di risonanza magnetica potrebbero essere utilizzati per valutare la qualità degli embrioni fertilizzati in-vitro. Il potenziale economico di questa particolare applicazione giustifica, da sola, investimenti in questa tecnologia. Un successo in questa direzione porterebbe benefici nei trattamenti della infertilità, possibilmente rendendoli piu' accessibili e affidabili. Altre applicazioni, al momento non identificate, potrebbero esistere.
Direct link to Lay Summary Last update: 26.09.2019

Lay Summary (English)

Lead
Nuclear Magnetic Resonance (NMR) is a powerful spectroscopic tool that allows for the inspection of chemistry in bulk matter. Renown for its bio-compatibility and non-invasive nature, NMR is today an established tool in bio-medical research and diagnostic medicine. The use of NMR at the scale of complex multicellular organisms, such as humans and mice, is already enabled and optimized by the existing commercial instrumentation. However, the use of this same technique at the scale typical of microorganisms and cells is hindered by the technical limitations of the conventional instrumentation. In this project we developed the first NMR instrument capable to operate at the microscopic scale of a human embryo and tested its capabilities on biological material.
Lay summary
Aim

In this project we implemented prototypes of NMR probes conceived for the microscopic scale of a single human embryo. Such technology delivered improved sensitivities at the microscopic scale combined with an exceptional degree of versatility. The use of this technology allows, for the first time, use of NMR on single mammalian embryos, micro-tissues and organoids. The technical development of the prototype focused on key aspects such as ease of use and compatibility with commonly used magnetic fields. A prototype with these characteristics allowed us to perform feasibility studies on stem-cells derived material and 3D organoids. The data retrieved are the "Proof of Concept" used to seek partnership with an IVF clinics to move towards pre-clincal and clinical studies for the application of this technology in the field of In Vitro Fertilisation (IVF).

Scientific and societal context

Besides the evident scientific interest, applications in the medical domain that can open to consistent markets are foreseen. A specific clinical field driving a large market is the one of fertility treatment, where such NMR probes can be used to assess the quality and health of embryos for in-vitro fertilization (IVF). A success in this direction would bring great benefits in IVF treatments by making them more accessible and reliable. 
Direct link to Lay Summary Last update: 26.09.2019

Responsible applicant and co-applicants

Name Institute

Employees

Collaboration

Group / person Country
Types of collaboration
Tecmag United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Industry/business/other use-inspired collaboration
Embryotools Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Industry/business/other use-inspired collaboration
InSphero AG Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Industry/business/other use-inspired collaboration
Giovanni Boero and Jürgen Brugger (LMIS1, EPFL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
CPMA Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Industry/business/other use-inspired collaboration
Prof. Denis Duboule (EPFL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ENC 2019 Poster CMOS-based sensors for micro-NMR: magnetic resonance at the embryo scale 07.04.2019 Monterey, CA, United States of America Grisi Marco; Conley Gaurasundar Marc;
New England NMR Discussion Group Individual talk CMOS-based sensors for microNMR: magnetic resonance at the embryo scale 12.03.2019 MIT, Boston, United States of America Conley Gaurasundar Marc; Grisi Marco;


Use-inspired outputs


Start-ups

Name Year

Abstract

Nuclear magnetic resonance (NMR) methods enable non-invasive studies of intact living matter. As a well-known example, magnetic resonance imaging (MRI) scanners are today an extremely powerful clinical diagnostic tool used in hospitals worldwide. Thanks to its non-invasive properties and resolving power, NMR has been successfully employed in applications such as diagnostic imaging, microscopy, and spectroscopy of large living animals. However, at the volume scales typical of microorganisms and cells, the use of the power of NMR is hindered by the sensitivity limitations of conventional instrumentation. In this project the instrument extending NMR studies to the scale of a single human embryo has been developed. This allows for cutting-edge applications such as real-time metabolism monitoring, drug intake studies, and selection of microorganisms based on endogenous chemistry. Besides the evident scientific interest, we foresee that our technology will allow for applications in the medical domain, opening to consistent markets. A specific clinical field driving a large market is the one of fertility treatment, where such NMR probes can be used to assess the quality and health of embryos for in-vitro fertilization (IVF). In this project we developed a first prototype NMR instrument ready to be delivered to laboratories, and protected the IP via a patent application. We are using this prototype to perform feasibility studies for IVF application, and we are in position to seek external partnerships for future pre-clinical and clinical studies. The technical development of the prototype focused on key aspects such as ease of use and broad compatibility with commonly used magnetic fields. The detection power of the device and its bio-compatibility have been successfully tested.
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