Device for detecting emission light of micro-object

• US 20050237524A1
• Filed: 02/28/2005
• Published: 10/27/2005
• Est. Priority Date: 03/01/2004
• Status: Active Grant

• Current Assignee: National Institute of Advanced Industrial Science and Technology (Government of Japan)
• Original Assignee: National Institute of Advanced Industrial Science and Technology (Government of Japan)
• Inventors: Itatani, Taro, Kamei, Toshihiro
• Granted Patent: US 7,489,401 B2
• Time in Patent Office: Days
• US Class Current: 356/318
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/6454 using an integrated detector array

Abstract

In the detection of fluorescence Lf emitted by a micro-object irradiated with an excitation light Le by a semiconductor light-detecting element 20, a converging microlens 62 for converging the excitation light Le elevating the optical density thereof and irradiating the micro-object with the light, causing the micro-object to generate fluorescence Lf due to two-photon absorption, is inserted partway along the light path of the excitation light Le. This enables the fluorescence Lf emitted by the micro-object to be detected with high sensitivity.

Claims

1. A micro-object emission light detecting device for detecting with a semiconductor light detecting element emission light emitted in the form of fluorescence or phosphorescence from the micro-object irradiated by excitation light emitted from an excitation light source;

characterized by comprising a converging microlens inserted partway along a light path of the excitation light to converge the excitation light and irradiate the micro-object with light of an elevated optical density and induce the micro-object to generate emission light from two-photon absorption.

5. A micro-object emission light detecting device according to any of claims 1 through 4, wherein the emission light emitted by said micro-object impinges on said semiconductor light detecting element via an optical filter possessing selective transmittance to said emission light.

6. A micro-object emission light detecting device according to any of claims 1 through 4, wherein said semiconductor light detecting element is integrated with a light-transparent chip that carries said micro-object.

7. A micro-object emission light detecting device according to any of claims 1 through 4, wherein said excitation light source is a surface emitting laser diode.

8. A micro-object emission light detecting device according to any of claims 1 through 4, wherein said semiconductor light-detecting element is a photodiode fabricated using a-Si:

H material.

9. A micro-object emission light detecting device according to any of claims 1 through 4, wherein said semiconductor light-detecting element is a photoconductor fabricated using a-Si:

H material.

10. A micro-object emission light detecting device according to any of claims 1 through 4, wherein said excitation light source and said semiconductor light-detecting element are integrated on the same substrate.

14. A micro-object emission light detecting device according to any of claims 1 through 4, characterized by said micro-object being a fluorophore or a semiconductor quantum dot or a micro-sample labeled with a fluorophore or a semiconductor quantum dot.

15. A micro-object emission light detecting device according to any of claims 1 through 4, wherein the wavelength of said excitation light is longer than the wavelength corresponding to a band gap of said semiconductor light detecting element and the wavelength of said emission light is shorter than the wavelength corresponding to a band gap of said semiconductor light detecting element.

23. A micro-object emission light detecting device according to any of claims 1, 16, 17, and 22, wherein said converging microlens is disposed on a substrate on which said semiconductor light detecting element is formed.

24. A micro-object emission light detecting device according to any of claims 1, 16, 17, and 22, wherein said converging microlens is formed on a light-transparent chip for carrying said micro-object.

25. A micro-object emission light detecting device according to claim 5, wherein the wavelength of said excitation light is a wavelength in the near infrared region.

26. A micro-object emission light detecting device according to claim 5, provided with a microlens for collecting emission light emitted from said micro-object, paralleling the collected light, and guiding the paralleled light to said optical filter.

27. A micro-object emission light detecting device according to claim 5, wherein at least the part of the side wall of said optical filter and said semiconductor light detecting element on which scattered light of said excitation light might fall incident is covered with a shielding layer.

28. A micro-object emission light detecting device according to claim 5, wherein the emission light detecting module comprised of said semiconductor light-detecting element and said optical filter, when viewed in a plan view, has a solid form of a circular or a polygonal shape with n vertices wherein n denotes an integer of not less than 3, said solid form has a part with a through hole of a circular or a polygonal shape with n vertices , and said excitation light passes through the interior of said through hole.

29. A micro-object emission light detecting device according to claim 5, wherein said semiconductor light detecting element is divided into a plurality of parts and the emission light emitted by said micro-object is passed through optical filters with different spectral characteristics and is impinged on each divided part of said semiconductor light detecting element.

2. A micro-object emission light detecting device for detecting with a semiconductor light detecting element emission light emitted in the form of fluorescence or phosphorescence from the micro-object irradiated by excitation light emitted from an excitation light source;

characterized by

comprising a micro-resonator constituted by a pair of mirrors inserted partway along a light path of the excitation light;

having the micro-object disposed between the pair of mirrors; and

utilizing the multiple reflection function of the micro-resonator to elevate the effective intensity of the excitation light and irradiating the micro-object with the excitation light of the elevated intensity to thereby induce the micro-object to generate emission light from two-photon absorption.

16. A micro-object emission light detecting device according to claim 2, wherein a converging microlens for converging said excitation light and injecting it into said micro-resonator is disposed, or a converging microlens for converging said excitation light and a concave lens for paralleling the excitation light converged thereby and injecting it into said micro-resonator are disposed partway along the light path between said excitation light source and said micro-resonator.

3. A micro-object emission light detecting device for detecting with a semiconductor light detecting element emission light emitted in the form of fluorescence or phosphorescence from a micro-object irradiated by excitation light emitted from an excitation light source;

characterized by

comprising a Q switch laser that generates a short pulse laser in response to the irradiation with the excitation light, elevating the peak light intensity instantaneously, and irradiating the micro-object with the short pulse laser beam as an excitation light to have the micro-object generate emission light from two-photon absorption.

17. A micro-object emission light detecting device according to claim 3, characterized by comprising a converging microlens that is inserted partway along the light path of said excitation light, and by converging said excitation light, and elevating the optical density and irradiating said micro-object with the light to induce said micro-object to emit said emission light from two-photon absorption.

18. A micro-object emission light detecting device according to claim 3, wherein said Q switch laser is a passive type comprising a gain medium and a saturable absorber.

19. A micro-object emission light detecting device according to claim 18, wherein the gain medium of said Q switch laser is a semiconductor with quantum well structure and the saturable absorber of said Q switch laser is also a semiconductor with quantum well structure.

20. A micro-object emission light detecting device according to claim 18, wherein the gain medium of said Q switch laser and the saturable absorber are quantum wells formed of InGaAs grown on a GaAs substrate, and the composition of the In and the Ga and the thickness of the InGaAs quantum well layer is so fixed as to give rise to an overlap between the gain curve of said gain medium and the absorption band of said saturable absorber.

21. A micro-object emission light detecting device according to claim 18, wherein the gain medium of said Q switch laser and the saturable absorber are monolithically integrated on the same semiconductor substrate.

4. A micro-object emission light detecting device for detecting with a semiconductor light detecting element emission light emitted in the form of fluorescence or phosphorescence from micro-object irradiated by excitation light emitted from an excitation light source;

characterized by

comprising an SHG element inserted into a resonator disposed partway along a light path of the excitation light for doubling frequency of light from the excitation light source and, by irradiating the micro-object with the frequency-doubled light, enabling the micro-object to generate emission light due to one-photon absorption.

22. A micro-object emission light detecting device according to claim 4, furnished with a converging microlens inserted partway along the light path of said excitation light to converge said excitation light, minimize the area of light irradiation, and irradiate said micro-object.

11. A micro-object emission light detecting device, characterized by having the combination of said semiconductor light detecting element and said excitation light source form one module and having a plurality of said modules arrayed one-dimensionally or two-dimensionally to form a module array.

12. A micro-object emission light detecting device, characterized by having the combination of said semiconductor light-detecting element and said excitation light source form one module and comprising a scanning mechanism for scanning said module in a one-dimensional direction or a two-dimensional direction, or in a three-dimensional direction.

13. A micro-object emission light detecting device, characterized by having the combination of said semiconductor light-detecting element and said excitation light source form one module, having a plurality of said modules arrayed one-dimensionally or two-dimensionally to form a module array, and comprising a scanning mechanism for scanning said modules in a one-dimensional direction or a two-dimensional direction, or in a three-dimensional direction.