DS0412 - Innovation médicale, nanotechnologies, médecine régénérative, thérapies et vaccins innovants

NOvel in vivo DEtection NanoSystems – NODENS

Intravascular 3D microdevice for the in vivo capture of rare circulating biomarkers

In the field coupling micro/nanotechnologies with life sciences, the use of advanced devices as highly sensitive biosensors is currently in a transfer phase towards the applicative realm of medicine. The expectations of the medical community with respect to these novel technologies is located in the sensitivity and specificity of such devices which could enable the early diagnosis of numerous diseases but also their monitoring through the detection of rare circulating biomarkers.

This project aims at fabricating an intravascular 3D microdevice, or microfilter, capable of capturing directly from the human bloodstream, cellular biomarkers of interest (circulating tumor cells).

We propose to take advantage of the fluidics of the bloodstream, in vivo, to capture these cellular biomarkers with improved sensitivity and response time and with no sampling bias. To that purpose we will i) integrate simulation and in vitro experimentation in the design and evaluation of an intravascular capture microdevice to address two conflicting objectives: preservation of the laminar flow and capture of CTCs making good use of the differential physical characteristics of CTCs to capture them, irrespective of their surface expression of inconstant epithelial/tumor markers. ii) The captured cells will then be manipulated and analyzed ex vivo at the single cell level, to allow subsequent cellular identification and molecular characterization while preserving them alive.

In practice, the idea is to fabricate a three-dimensional capture device using a 3D laser lithography method (equipment available in the cleanroom facility of the LAAS-CNRS, as part of the RENATECH network). The fluidic test benches are fabricated using polymeric replication of structured molds (soft-lithography). Devices are characterized using live optical microscopy, confocal imaging and scanning electron microscopy.

We succeeded in implementing a platform mimicking in vivo conditions to evaluate the performance of our micro devices. Using the designed capture micro device, we succeeded in isolating selectively and efficiently prostate cancer cell lines from whole blood without any obstruction or coagulation observed, and without any prior dilution or treatment of the blood required.
We also succeeded in integrating the micro device onto an insertion guide wire adapted to intravenous medical catheters for a potential validation and future use in vivo.

We anticipate this device could be used for prognosis and for personalized therapeutic follow-up in clinical routine. Its versatility should render it transposable to the capture of other circulating cellular and molecular biomarkers.

- Patent: PCT/FR2016/050218

In the field coupling micro/nanotechnologies with life sciences and analytical techniques, the use of advanced nanodevices as highly sensitive biosensors is currently in a transfer phase towards the applicative realm of medicine. The expectations of the medical community with respect to these novel technologies is located in the sensitivity and specificity of such devices which could enable the early diagnosis of numerous diseases but also their monitoring through the detection of rare circulating biomarkers. The biomarkers targeted in this project are circulating tumor cells. In this context, this project aims at fabricating an intravascular 3D microdevice, or microfilter, capable of capturing in vivo, directly from the human bloodstream, the cells of interest. The so-collected cells will be kept alive and further analyzed at the single-cell level using a droplet microfluidic platform ex vivo.

Project coordination

Aline CERF (Centre National de la Recherche Scientifique - Laboratoire d'Analyse et d'Architecture des Systemes)

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

CNRS/LAAS Centre National de la Recherche Scientifique - Laboratoire d'Analyse et d'Architecture des Systemes

Help of the ANR 271,128 euros
Beginning and duration of the scientific project: September 2015 - 48 Months

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