Microscopy imaging device with advanced imaging properties

1. An epifluorescence microscope comprising:

an image capture circuit including an array of optical sensors; and

an optical arrangement configured (i) to direct excitation light of less than about 1 mW over an area that is at least 0.5 mm 2 encompassed within a field of view which comprises a target object, and (ii) to direct epi-fluorescence emission caused by the excitation light to the array of optical sensors, the optical arrangement and array of optical sensors each being sufficiently close to the target object to provide at least 2.5 μm resolution for an image of the field of view.

2. The microscope of claim 1 , wherein the optical arrangement includes an objective lens, a light-emitting-diode, and a CMOS image sensor array, each contained within an integrated housing of the microscope that is less than a cubic inch in size.

3. The microscope of claim 1 , wherein the optical arrangement includes an objective lens, a light-emitting diode, and a CMOS image sensor array, each contained within an integrated housing, wherein the optical arrangement and array of optical sensors weighs less than 2 grams.

4. The microscope of claim 1 , wherein optical magnification at the image capture circuit and of the target object is less than or equal to 5.

5. The microscope of claim 1 , wherein the optical arrangement is configured to provide self-alignment between a light source providing the excitation light, the array of optical sensors and an objective lens.

6. The microscope of claim 1 , wherein the optical arrangement is configured to provide focusing of an image by adjustment of a distance between the array of optical sensors and an objective lens during real-time imaging.

7. The microscope of claim 1 , further including at least one optical filter element and light source generating the excitation light, and wherein the at least one optical filter element, the light source and the array of optical sensors is configured to detach and reattached to the microscope.

8. The microscope of claim 1 , wherein the optical arrangement and the array of optical sensors are each sufficiently close to the target object to provide at least 2.5 μm resolution for generation of images of the field of view at a rate of at least 36 Hz.

9. An epifluorescence microscope comprising:

an optical light source configured to produce excitation light from an energy source that provides less than 6 mW, wherein the excitation light is directed over an area that is at least 0.5 mm 2 encompassed within a field of view which comprises a target object;

an imaging circuit including a sensor array; and

an objective lens configured to operate sufficiently close to the optical light source, the image sensor array and the target object to provide at least a 2.5 μm resolution image of the field of view that is at least 0.5 mm 2 .

10. An epifluorescence microscope, the microscope comprising:

an optical excitation arrangement configured to direct light over an area that is at least 0.5 mm 2 encompassed within a field of view containing an imaging target;

an imaging circuit including an optical sensor array configured to generate image data from fluorescence caused by an interaction between the directed light and the imaging target; and

an optical arrangement configured to direct the fluorescence to the optical sensor array with sufficient intensity and focus for the image data to depict over 0.5 mm 2 and at least 2.5 μm resolution,

wherein the epifluorescence microscope is less than a cubic inch in size.

11. A method of using the epifluorescence microscope of claim 1 , comprising the steps of attaching and reattaching the epifluorescence microscope to a base plate of a supportive structure for allowing precise microscope alignment for repeated imaging of a common imaging location during chronic experiments.

12. The microscope of claim 2 , wherein the microscope including the image capture circuit and the optical arrangement, weighs less than 2 grams, and wherein the light-emitting diode contained within the housing provides the excitation light.

13. The microscope of claim 1 , wherein the optical arrangement includes an objective lens and a light source emitting the excitation light and is contained within a housing of the microscope that is less than a cubic inch in size; and wherein the image capture circuit and the optical arrangement including the light source, weigh less than 2 grams.

14. The microscope of claim 13 , wherein the excitation light provided by the light source is directed to the objective lens by one or more excitation elements of the optical arrangement.

15. The microscope of claim 14 , wherein the objective lens is configured to direct the excitation light to the target object and focus the excitation light onto the field of view.

16. The microscope of claim 15 , wherein the optical arrangement further includes one or more emission elements configured to provide a focal plane from epifluorescent emission light received from the target object via the objective lens.

17. The microscope of claim 16 , wherein the image capture circuit is provided at the focal plane and configured to capture the image of the field of view that includes multiple individual capillary blood vessels with sufficient resolution to distinguish individual capillary blood vessels from one another.

18. The microscope of claim 17 wherein the image of the field of view has sufficient resolution to distinguish individual erythrocytes flowing through the individual capillary blood vessels.

19. The microscope of claim 17 wherein the one or more emission elements includes an achromatic lens located between the objective lens and the image capture circuit, wherein the achromatic lens receives collimated epifluorescent light from the objective lens and focuses the collimated epifluorescent light onto the focal plane at which the image capture circuit is provided.

20. The microscope of claim 13 , wherein the target object is a brain of a mouse and the microscope is configured to be mounted on a head of the mouse and provide in vivo brain imaging during awake behavior.

21. The microscope of claim 20 , wherein the awake behavior includes locomotion of the mouse, and the image of the field of view includes multiple individual capillary blood vessels of the brain of the mouse with sufficient resolution to distinguish individual capillary blood vessels from one another during the locomotion.

22. The microscope of claim 17 , wherein a distance from the objective lens to the field of view of the target object so that the image of the field of view is in focus is 50-250 μm.

23. The microscope of claim 13 , wherein a distance from the objective lens to the image capture circuit is less than 1 inch.

24. The microscope of claim 15 , wherein the excitation light is provided from the light source within the housing to the target object without use of a fiber optic.

25. The microscope of claim 13 , wherein no fiber optics are provided within the housing.

26. The microscope of claim 13 , wherein the housing is formed from a black material or includes a layer of absorbent material.

27. The microscope of claim 17 , wherein the housing comprises a threaded interface between a portion of the housing holding the image capture circuit and a portion of the housing holding the objective lens, the threaded interface configured to provide fine adjustment of a distance between the image capture circuit and the objective lens to adjust the focal plane.

28. The microscope of claim 17 , wherein the optical arrangement includes a dichroic mirror configured to reflect the excitation light from the light source to the objective lens and to pass the epifluorescent emission light from objective lens to the image capture circuit.

29. The microscope of claim 13 , further comprising a synchronization circuit that interfaces with an external device that displays the image of the field of view.

30. The microscope of claim 29 , wherein the external device provides control of the light source.

31. The microscope of claim 2 , wherein the objective lens is a gradient refractive index (GRIN) lens.

32. The microscope of claim 2 , wherein the objective lens is a gradient refractive index (GRIN) lens which has at least one of the following characteristics: a diameter of about 2 mm, a pitch length of about 0.245, or a numerical aperture of about 0.45.

33. The microscope of claim 13 , wherein the microscope is configured and arranged to capture video images of the field of view of the target object.

34. The microscope of claim 9 , further comprising a housing that is less than one cubic inch in size, the housing containing the imaging circuit and the optical light source.

35. The microscope of claim 34 , wherein the objective lens is configured to direct collimated excitation light from the target object.

36. The microscope of claim 10 , further comprising a housing that is less than the cubic inch, the housing containing the imaging circuit, and wherein the microscope weighs less than 2 grams.

37. The microscope of claim 36 , further comprising a light source providing the light, said light source contained within the housing.

38. The microscope of claim 36 , further comprising an interface configured to communicate with an external optical data recording/configuring system.

39. The microscope of claim 36 , wherein the microscope is configured and arranged to capture sequential images of the imaging target at a rate of at least 50 Hz.