Method for simultaneously detecting fluorescence and raman signals for multiple fluorescence and raman signal targets, and medical imaging device for simultaneously detecting multiple targets using the method

Patent metadata

Field	Value
Publication number	US-9833145-B2
Application number	US-201715398038-A
Country	US
Kind code	B2
Filing date	Jan 4, 2017
Priority date	Aug 11, 2010
Publication date	Dec 5, 2017
Grant date	Dec 5, 2017

Abstract

Provided are a method for simultaneously detecting fluorescence and Raman signals for multiple fluorescence and Raman signal targets, and a medical imaging device for simultaneously detecting multiple targets using the method. The method includes: injecting at least one marker particle comprising Raman markers and receptors into the body of an animal, which can be a human; irradiating a laser beam onto the body of the animal; and detecting the optical signals emitted by the marker particle after the irradiation of the laser beam separately as fluorescence signals and Raman signals. The simultaneous detection of multiple targets may be performed even without scanning optical signals emitted by the marker particle individually with different optical fibers. As an examination may be performed by injecting surface-enhanced Raman marker particles, weak Raman signals may be augmented so as to obtain a more accurate diagnosis result in real time.

First claim

What is claimed is:

1. A method for simultaneously detecting, by a medical imaging device, fluorescence signals and Raman signals for multiple targets in a test structure inside a body of an animal, the method comprising steps of:
directly spraying a plurality of marker particles onto the test structure, each marker particle being adapted to simultaneously generate fluorescence signals in a first wavelength range and Raman signals in a second wavelength range and including one or more Raman marker particles, receptors, one or more fluorescence dyes and one or more metallic nanoparticles comprising at least one of silver (Ag), gold (Au) or copper (Cu), the first and second wavelength ranges being separate from one another without mutual interference;
emitting a laser light onto the test structure inside the body of the animal so that one or more of the marker particles sprayed onto the test structure emit optical signals comprising the fluorescence signals and the Raman signals;
collecting, by an optical fiber bundle of the medical imaging device, the optical signals emitted from the one or more of the marker particles sprayed onto the test structure;
separating the optical signals into a first optical path containing the fluorescence signals in the first wavelength range and a second optical path containing the Raman signals in the second wavelength range; and
simultaneously detecting the fluorescence signals in the first optical path for constructing a fluorescence image indicative of locations of the multiple targets in the test structure based on the detected fluorescence signals, and the Raman signals in the second optical path for constructing a SERS (Surface Enhanced Raman Scattering) spectrum indicative of types of the multiple targets in the test structure based on the detected Raman signals.

2. The method of claim 1 , wherein in said emitting step, the emitted optical signals further contain scattered laser light, and before said separating step, further comprising a step of:
removing, by filtering, the scattered laser light from the emitted optical signals to form a filtered optical signal.

3. The method of claim 1 , wherein each of the marker particles further comprises a silica shell surrounding the one or more fluorescence dyes, the one or more Raman marker particles and the one or more metallic nanoparticles.

4. The method of claim 3 , wherein each of the marker particles further comprises a core particle which is surrounded by the one or more fluorescence dyes, the one or more Raman marker particles, the one or more metallic nanoparticles and the silica shell, and which is formed of at least one of silica and magnetic materials.

5. The method of claim 1 , wherein each of the marker particles further comprises a core particle and wherein the one or more Raman marker particles and the one or more metallic nanoparticles are dispersed inside the core particle.

6. The method of claim 1 , wherein the animal comprises a human.

7. The method of claim 1 , wherein the fluorescence dye comprises n types of fluorescence dyes and the Raman marker particles comprises m types of Raman marker particles, wherein the plurality of marker particles is capable of indicating m×n types of targets in the test structure, and wherein m is an integer greater than or equal to 1 and n is an integer ranging from 2 to 4.

8. A medical imaging device for simultaneously detecting fluorescence signals and Raman signals for a plurality of targets in a test structure inside a body of an animal, the medical imaging device comprising:
a plurality of marker particles, each marker particle being adapted to simultaneously generate fluorescence signals in a first wavelength range and Raman signals in a second wavelength range and including one or more Raman marker particles, one or more receptors, one or more fluorescence dyes and one or more metallic nanoparticles comprising at least one of silver (Ag), gold (Au) or copper (Cu), wherein the first and second wavelength ranges are separate from one another without mutual interference;
a spray device adapted to spray the plurality of marker particles onto the test structure;
a probe including an optical fiber bundle configured to guide a laser light onto the test structure and collect optical signals comprising the fluorescence signals and the Raman signals emitted from one or more of the marker particles sprayed onto the test structure in response to the laser light;
a scanner connected to the probe and adapted to scan the optical signals comprising the fluorescence signals and the Raman signals;
a light separator comprising a beam splitter connected to the scanner to separate a path of the optical signals into a first path including the fluorescence signals in the first wavelength range and a second path including the Raman signals in the second wavelength range;
a fluorescence signal detector configured to detect the fluorescence signals from the optical signals in the first path for constructing a fluorescence image indicative of locations of the plurality of targets in the test structure based on the detected fluorescence signals; and
a Raman signal detector configured to detect the Raman signals from the optical signals in the second path for constructing a SERS (Surface Enhanced Raman Scattering) spectrum indicative of types of the plurality of targets in the test structure based on the detected Raman signals.

9. The medical imaging device of claim 8 , wherein the light separator further comprises an edge filter placed between the scanner, the fluorescence signal detector and the Raman signal detector, to remove, by filtering, the laser light from the optical signals incoming from the scanner.

10. The medical imaging device of claim 8 , wherein each of the marker particles further comprises a silica shell surrounding the one or more fluorescence dyes, the one or more Raman marker particles and the one or more metallic nanoparticles.

11. The medical imaging device of claim 10 , wherein each of the marker particles further comprises a core particle which is surrounded by the one or more fluorescence dyes, the one or more Raman marker particles, the one or more metallic nanoparticles and the silica shell, and the core particle is formed of at least one of silica and magnetic materials.

12. The medical imaging device of claim 8 , wherein each of the marker particles further comprises a core particle and wherein the one or more Raman marker particles and the one or more metallic nanoparticles are dispersed inside the core particle.

13. The medical imaging device of claim 8 , wherein the receptors comprise any one selected from the group consisting of enzymatic substrate, ligand, amino acid, peptide, protein, nucleic acid, lipid, co-factor, carbohydrate and antibody.

14. The medical imaging device of claim 8 , wherein the fluorescence dye comprises n types of fluorescence dyes and the Raman marker particles comprises m types of Raman marker particles, wherein the plurality of marker particles is capable of indicating m×n types of targets in the test structure, and wherein m is an integer greater than or equal to 1 and n is an integer ranging from 2 to 4.

Assignees

• Snu R&Db Foundation

Inventors

• Jeong Dae Hong
• Kang Keon Wook
• Lee Dong Soo
• Lee Yoon Sik
• Kim Gun Sung
• Jun Bong Hyun
• Paeng Jin Chul
• Lee Ho Young
• Lee Yun Sang

Classifications

• A61B1/000095

  for image enhancement · CPC title

• A61M2205/0244

  Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology · CPC title

• A61K49/0093

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title

• A61K49/0002

  General or multifunctional contrast agents, e.g. chelated agents · CPC title

• A61K49/00

  Preparations for testing in vivo · CPC title