Methods and apparatus for high-throughput label-free cell assay

Patent metadata

Field	Value
Publication number	US-2016109352-A1
Application number	US-201514680231-A
Country	US
Kind code	A1
Filing date	Apr 7, 2015
Priority date	Apr 17, 2014
Publication date	Apr 21, 2016
Grant date	—

Abstract

The present invention relates to a high-throughput label-free cell assay system which scans a lower part of medium made of glass using an object lens and a Galvano mirror and using a broadband laser as a light source, analyzes and visualizes light reflected from the lower part of the medium using a spectrometer, measures interference spectra formed by the light reflected from each interface of the medium using the spectrometer, and measures phase from data that the measured interference spectra were converted by Fourier transform to observe structural change of cells. The system includes a transparent medium on which a sample is put, an object lens located beneath the transparent medium; a Galvano mirror located beneath the object lens; an optical fiber coupler transferring light from the super-continuum light source to the Galvano mirror; and the spectrometer detecting spectrum of the light from the optical fiber coupler.

First claim

What is claimed is:

1 . A high-throughput label-free cell assay system comprising:
a transparent medium on which a sample is put and of which the bottom is transparent; an object lens which is located beneath the transparent medium; a Galvano mirror which is located beneath the object lens, has two mirrors, sends light incident from a super-continuum light source through an optical fiber coupler to the transparent medium through the object lens, and sends light returning from the transparent medium through the object lens to an optical fiber coupler while the two mirrors rotate; an optical fiber coupler which transfers light incident from the super-continuum light source to the Galvano mirror and transfers light incident from the Galvano mirror to a spectrometer; and the spectrometer which detects a spectrum of the light incident from the optical fiber coupler to output an image and to output an image of an interference spectrum formed by causing interference by the sample and the transparent medium.

2 . The high-throughput label-free cell assay system according to claim 1 , further comprising:
an operation processing part which receives the image of the interference spectrum from the spectrometer and measures phase through Fourier transform.

3 . The high-throughput label-free cell assay system according to claim 2 , further comprising:
a filter which is located between the super-continuum light source and the optical fiber coupler to output light of a predetermined wavelength band by filtering the light from the super-continuum light source.

4 . The high-throughput label-free cell assay system according to claim 3 , further comprising:
a first collimator located between the filter and the optical fiber coupler to transfer the light incident from the filter to the optical fiber coupler through an optical fiber connected to the optical fiber coupler.

5 . The high-throughput label-free cell assay system according to claim 2 , further comprising:
a second collimator located between the optical fiber coupler and the Galmano mirror to transfer the light exiting through the optical fiber connected to the optical fiber coupler to the Galmano mirror.

6 . The high-throughput label-free cell assay system according to claim 1 , further comprising:
a magnifier part which is located between the Galmano mirror and the object lens and has a convex lens.

7 . The high-throughput label-free cell assay system according to claim 6 , wherein the magnifier part forms a confocal photosystem using a first convex lens and a second convex lens, and the caliber of the first convex lens is smaller than the caliber of the second convex lens.

8 . The high-throughput label-free cell assay system according to claim 1 , wherein the super-continuum light source is a laser which releases broadband wavelengths of 0.4 to 2.2 μm.

9 . The high-throughput label-free cell assay system according to claim 1 , wherein the transparent medium is formed in a flat plane plate shape.

10 . The high-throughput label-free cell assay system according to claim 1 , wherein the image of the interference spectrum is obtained when the light incident onto the transparent medium through the object lens is reflected from the sample and interference occurs by a boundary between the sample and the transparent medium.

11 . The high-throughput label-free cell assay system according to claim 1 , wherein the super-continuum light source is one of a tungsten lamp, a tungsten halogen lamp, a xenon lamp, a super-luminescent diode, a Ti-sapphire laser and a wavelength swept laser.

12 . A high-throughput label-free cell assay method comprising:
a first step of transferring light exiting from a super-continuum light source to an optical fiber coupler through a filter and a first collimator; a second step of transferring the light transferred in the first step to a Galvano mirror through a second collimator by the optical fiber coupler; a third step of transferring the light transferred in the second step to a magnifier part while mirrors of a Galvano mirror rotate and transferring the incident light to the sample put on the transparent medium through the object lens and the transparent medium by the magnifier part; a fourth step of reflecting the incident light from the sample and transferring the reflected light to the Galvano mirror through the magnifier part after passing through the transparent medium and the object lens; a fifth step of transferring the transferred light to the optical fiber coupler through a second collimator while the mirrors of the Galvano mirror rotate; a sixth step of transferring the transferred light to a spectrometer by the optical fiber coupler; and a seventh step of detecting a spectrum of the incident light and outputting an image by the spectrometer and outputting an image of an interference spectrum formed by causing interference by the sample and the transparent medium.

13 . The high-throughput label-free cell assay method according to claim 12 , further comprising:
an eighth step of carrying out Fourier transform when an operation processing part receives the image of the interference spectrum to measure phase.

14 . The high-throughput label-free cell assay method according to claim 12 , wherein the image of the interference spectrum is obtained when the light incident onto the transparent medium through the object lens is reflected from the sample and interference is caused by the boundary between the sample and the transparent medium.

Assignees

• Univ Yonsei Iacf

Inventors

• Joo Chulmin
• Ryu Su Ho

Classifications

• G01N21/255

  Details, e.g. use of specially adapted sources, lighting or optical systems · CPC title

• G01N2015/1006

  for cytology · CPC title

• G01N15/1434 Primary

  Optical arrangements · CPC title

• G01N21/25 Primary

  Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands · CPC title

• G01N15/1456

  without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals · CPC title