Systems and methods of using anisotropic nanostructures in microfluidic devices for binding and optional release of molecules and cells

Patent metadata

Field	Value
Publication number	US-12005448-B2
Application number	US-201917268955-A
Country	US
Kind code	B2
Filing date	Aug 16, 2019
Priority date	Aug 17, 2018
Publication date	Jun 11, 2024
Grant date	Jun 11, 2024

Abstract

Systems and methods are disclosed that utilize metal nanostructures that are synthesized in situ along the internal surfaces of a microfluidic device. The nanostructures are formed by initial deposition of metallic seeds followed by flowing growth and reducing agent solutions into the capillaries/microfluidic channels to grow the nanostars. The nanostructures may optionally be functionalized with a capture ligand. The capture ligand may be used to selectively bind to certain cells (e.g., circulating tumor cells). The cells may be removed by a beam of light (e.g., laser beam) that induces localized heating at the surface location(s) containing the nanostructures. The plasmonic nature of the nanostructures can be used to heat the nanostructure(s) locally for the selective removal of one or certain cells. The nanostructures may be used to acquire Raman spectra of molecules or other small objects that are bound thereto for identification and quantification.

First claim

What is claimed is:

1. A microfluidic device for the selective capture and release of cells comprising:
one or more microfluidic channels or capillaries having one or more inner surfaces functionalized with a plurality of in-situ grown gold anisotropic nanostars disposed thereon, wherein the gold anisotropic nanostars exhibit plasmonic activity in one or more wavelength ranges and further comprise a capture ligands specific to a specific type of cell:
one or more pumps configured to pump a sample containing the cells through the one or more microfluidic channels or capillaries, wherein at least some of the cells adhere to the capture ligands; and
a light source configured to deliver a focused beam of light onto the one or more inner surfaces functionalized with the plurality of in-situ grown gold anisotropic nanostars, wherein the focused beam of light is configured to produce localized heating on the gold anisotropic nanostars, which is configured to cause conformation changes in the gold anisotropic nanostars to release the at least some of the cells that adhere to the capture ligands.

2. The microfluidic device of claim 1 , wherein one or more of wavelength ranges comprises the near-infrared wavelength range.

3. The microfluidic device of claim 1 , wherein the capture ligands comprise an antibody or aptamer.

4. A system comprising the microfluidic device of claim 1 , further comprising a Raman spectrometer or Raman microscope configured to obtain Raman spectra or to obtain Raman images of the cells that adhere to the capture ligands.

5. The system of claim 4 , wherein the Raman spectra, Raman images, or spectral data is enhanced by the gold anisotropic nanostars disposed on the inner surface of the one or more microfluidic channels or capillaries.

6. The system of claim 4 , further comprising a computing device, the computing device containing software executed thereon that identifies the cell type based on the Raman spectra, Raman images obtained by the Raman spectrometer or Raman microscope.

7. A system comprising the microfluidic device of claim 1 , further comprising an optical microscope configured to image the cells that adhere to the capture ligands.

8. The system of claim 7 , wherein the optical microscope comprises a fluorescent microscope.

9. The system of claim 7 , wherein the optical microscope comprises a confocal microscope.

10. The microfluidic device of claim 1 , wherein the light source comprises one or more of a laser, light emitting diode (LED), or laser diode.

11. A method of using the microfluidic device of claim 1 , comprising pumping the sample through the one or more microfluidic channels or capillaries having one or more cells, wherein one or more of the cells adheres to the gold anisotropic nanostars via the capture ligand.

12. The method of claim 11 , further comprising releasing one or more of the adherent cells from the gold anisotropic nanostars by increasing the local temperature with the focused beam of light from the light source directed at one or more target sites on the one or more microfluidic channels or capillaries.

13. The method of claim 12 , wherein the focused beam of light is scanned relative to the one or more inner surfaces functionalized with the plurality of in-situ grown gold anisotropic nanostars.

14. The method of claim 12 , wherein the focused beam of light is directed at one or more target sites while fluid is pumped through the one or more microfluidic channels or capillaries.

Assignees

• Univ California

Inventors

• Scarabelli Leonardo
• Vinnacombe Gail
• Heidenreich Liv
• Chiang Naihao
• Gong Yao
• Weiss Paul S
• Jonas Steven J

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G02B21/16

  adapted for ultraviolet illumination {; Fluorescence microscopes (G02B21/0076 takes precedence)} · CPC title

• G02B21/006

  focusing arrangements; selection of the plane to be imaged · CPC title

• G01N2021/656

  Raman microprobe · CPC title

• G01N33/54346

  Nanoparticles · CPC title