Detecting and Using Light Representative of a Sample

Abstract

An imaging device includes light sensitive locations that are separately sensitive to light received at a surface with respect to a portion of a sample associated with the surface, the light sensitive locations having a resolution of 5 microns or smaller. There is a device to associate the portion of the sample with the surface. The imaging device and a distance of the portion of the sample to the light sensitive locations are such that usable useful image of the portion of the sample can be acquired directly by operation of the imaging device. An imaging device includes light sensitive sources that are separately able to deliver light with respect to a portion of a sample associated with the surface. The light source locations having a resolution of 5 microns or smaller. There is a device to associate the portion of the sample with the surface. The imaging device and a distance of the portion of the sample to the light source locations are such that a useful image of the portion of the sample can be acquired directly by operation of the imaging device. An imaging device can include both the light source locations and the light source locations and the light sensitive locations.

1 . An apparatus comprising
 a surface with which a portion of a sample can be associated,   an imaging device that comprises light sensitive locations that are separately sensitive to light received at the surface with respect to the portion of the sample associated with the surface, the light sensitive locations having a resolution of 2 microns or smaller,   a device to associate the portion of the sample with the surface, and   the resolution of the imaging device and a distance of the portion of the sample to the light sensitive locations being such that a useful image of the portion of the sample can be acquired directly by operation of the imaging device.   
     
     
         2 . An apparatus comprising
 a surface with which a portion of a sample can be associated,   an imaging device that comprises light source locations that are separately able to deliver light with respect to the portion of the sample, the light source locations having a resolution of 2 microns or smaller, and with a light detector to receive light from the light source locations and the sample,   the imaging device and a distance of the portion of the sample to the light source locations being such that a useful image of the portion of the sample can be acquired directly by operation of the imaging device.   
     
     
         3 . The apparatus of  claim 1  comprising an absorbance spectroscopy element to process wavelength-dependent information from the imaging device. 
     
     
         4 . The apparatus of  claim 3  in which the sample is homogeneous and a single image from the imaging device is sufficient for absorbance spectroscopy processing. 
     
     
         5 . The apparatus of  claim 3  in which the sample is heterogeneous and flows past the imaging device, multiple images are captured by the imaging device, and the absorbance spectroscopy element processes the images together. 
     
     
         6 . The apparatus of  claim 1  comprising a light amplifier. 
     
     
         7 . The apparatus of  claim 1  in which the device to associate the portion of the sample with the surface comprises a chamber that encompasses at least a portion of the surface with which the portion of the sample is associated and is to contain the portion of the sample. 
     
     
         8 . The apparatus of  claim 1  in which the device comprises elements for causing units of interest in the portion of the sample to tend to be located closer to the surface than other elements of the portion of the sample. 
     
     
         9 . The apparatus of  claim 1  in which the device to associate the portion of the sample with the surface comprises a lid. 
     
     
         10 . The apparatus of  claim 9  in which the lid is transparent to light. 
     
     
         11 . The apparatus of  claim 9  in which the lid comprises a bottom surface arranged to touch the sample. 
     
     
         12 . The apparatus of  claim 9  in which the lid is disposable and comprises spots of binding units that are to be aligned with the light sensitive locations of the imaging device. 
     
     
         13 . The apparatus of  claim 9  in which the lid is suspended from an aperture in a balloon, the perimeter of which is attached at or near the imaging device. 
     
     
         14 . The apparatus of  claim 9  comprising spots of binding units that are deposited directly onto the pixels and aligned with the light sensitive locations of the imaging device. 
     
     
         15 . The apparatus of  claim 11  in which the bottom surface of the lid and the surface with which the portion of the sample is associated are not parallel. 
     
     
         16 . The apparatus of  claim 11  in which the bottom surface of the lid is convex relative to the surface associated with the portion of the sample. 
     
     
         17 . The apparatus of  claim 11  comprising a mechanism to lower the lid smoothly and maintain its bottom parallel to the surface. 
     
     
         18 . The apparatus of  claim 11  comprising a mechanism to measure the volume of the sample space in the chamber. 
     
     
         19 . The apparatus of  claim 18  in which the mechanism comprises at least one of absorbance using a known concentration of dye, counting of microbeads added in known concentration, and trigonometry with markers/spots on the bottom surface of the chamber lid illuminated from different positions. 
     
     
         20 . The apparatus of  claim 1  comprising a device to associate the portion of the sample with the surface and arranged to define a sample space in which the sample space comprises a precisely known volume at the surface. 
     
     
         21 . The apparatus of  claim 20  in which the portion of the sample contains sample units and the sample space extends from the surface by a distance that corresponds to a size of the sample units. 
     
     
         22 . The apparatus of  claim 1  comprising a device to associate the portion of the sample with the surface and arranged to define a sample space, in which the device to associate the portion of the sample with the surface comprises a flow inlet and a flow outlet. 
     
     
         23 . The apparatus of  claim 1  comprising an illuminator. 
     
     
         24 . The apparatus of  claim 23  in which the illuminator is to deliver collimated light toward the surface. 
     
     
         25 . The apparatus of  claim 24  in which the illuminator comprises a multi-point illuminator with light collimated toward the surface by anamorphic reflectors or an anamorphic prism. 
     
     
         26 . The apparatus of  claim 1  comprising a treatment of or on the surface. 
     
     
         27 . The apparatus of  claim 26  in which the treatment comprises an abrasion resistance material. 
     
     
         28 . The apparatus of  claim 1  comprising a tool on which the imaging device is mounted. 
     
     
         29 . The apparatus of  claim 28  in which the tool is elongated to fit within an enclosed space. 
     
     
         30 . The apparatus of  claim 28  in which the tool comprises an illuminator. 
     
     
         31 . The apparatus of  claim 1  comprising a layer on the surface to receive light at an edge of the layer and propagate it to a vicinity of the light sensitive locations. 
     
     
         32 . The apparatus of  claim 1  comprising a pipette to contain the sample in a chamber at the surface. 
     
     
         33 . The apparatus of  claim 31  in which the layer conducts surface plasmon illumination to the portion of the sample. 
     
     
         34 . The apparatus of  claim 31  in which the layer comprises a totally internally reflective layer on the surface to provide illumination as an evanescent wave to the portion of the sample. 
     
     
         35 . The apparatus of  claim 1  comprising an acoustic resonator to cause units of interest in the portion of the sample to move within the sample relative to the surface. 
     
     
         36 . An apparatus comprising
 a device configured to enable a sample of a person or animal who is the subject of health care to be placed at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both, and   electronics to cause information about the sample to be captured at a resolution of 2 microns or smaller by the device using light and to be provided for use in health care of the person or animal.   
     
     
         37 . The apparatus of  claim 36  comprising a processor to process the information captured about the sample to generate results associated with units contained in the sample, and in which the processor measures units contained in the sample, and the measurement is of at least one of volume, size, shape, length, luminescence, fluorescence, scattering, birefringence, or other optical property. 
     
     
         38 . An apparatus comprising
 a device configured to enable a surface of the device to be placed on or in the vicinity of tissue or material of a person or animal who is a subject of health care at a location, the surface being associated with a dense array of light sensitive locations or light emitting locations or both, and   electronics to cause information about the sample to be captured at a resolution of 2 microns or smaller by the device using light at the location and to be provided for use in the health care.   
     
     
         39 . The apparatus of  claim 38  comprising
 a communication facility for transmission of the information to a remote location for analysis of the information. 
 
     
     
         40 . The apparatus of  claim 38  in which the device is configured to enable a surface of the device to be placed into contact with tissue or cells at a surgical site of the person or animal during a surgical procedure. 
     
     
         41 . A method of using the apparatus of  claim 38  comprising causing information about the sample to be captured dynamically by the device using light at the location. 
     
     
         42 . The method of  claim 1  in which the sample comprises biological cells and the method comprises using light to excite fluorescence and monitoring at least one of: dynamic changes in tissue metabolism, ion levels, membrane electrical potential, redox state, cellular energetics. 
     
     
         43 . The apparatus of  claim 38  comprising a mechanism that enables illumination to be provided from alongside the surface of the device or from points interspersed across the surface, at least partly through tissue of the person. 
     
     
         44 . A method comprising
 placing a sample of a person or animal who is the subject of health care at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,   deriving information at a resolution of 2 microns or smaller about the sample from the device using light, and   detecting a cell type using antibodies or other specific binding molecules directed against surface antigens of cells of a cell type in the sample.   
     
     
         45 . A method comprising
 placing a sample of a person or animal who is the subject of health care at a surface of a device,   deriving information about the sample at a resolution of 2 microns or smaller from the device using light, and   generating a blood count analysis from the derived information.   
     
     
         46 . A method comprising
 placing a sample of a person or animal who is the subject of health care at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,   deriving image information about the sample at a resolution of 5 microns or smaller from the device, and   diagnosing a parasitic disease using the derived image information.   
     
     
         47 . A method comprising
 placing a sample of a person or animal at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,   deriving information about the sample at a resolution of 2 microns or smaller from the device, and   using the derived information to perform an assay of a cell function.   
     
     
         48 . A method comprising
 placing a sample of a person or animal who is the subject of health care at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,   deriving information about the sample at a resolution of 5 microns or smaller from the device, and   performing cytogenetics using the derived information.   
     
     
         49 . A method comprising
 placing a sample of a person or animal who is the subject of health care at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,   deriving information about the sample from the device,   and performing massively parallel biochemical analysis of the sample.   
     
     
         50 . A method comprising
 placing a non-blood fluid, cellular, particulate, or other biochemical sample at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,   deriving information about the sample at a resolution of 2 microns or smaller from the device, and   analyzing the sample based on the derived information.   
     
     
         51 . An apparatus comprising
 a disposable imager comprising
 a device configured to enable a sample to be placed at a surface of the device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both, 
 electronics to cause information about the sample to be captured at a resolution of 2 microns or smaller by the device using light, 
 a mechanism to contain the sample at the surface of the device, and 
 a coupler to connect and disconnect the disposable imager with a processing unit to process the captured information, the coupler enabling the disposable imager to be removed from the processing unit and replaced by another disposable imager. 
   
     
     
         52 . A method of using the apparatus of  claim 51  comprising
 applying the sample to the surface of the device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both, 
 capturing the information about the sample, and 
 sending the captured information to the processing unit for processing. 
 
     
     
         53 . A method comprising
 associating a sample with a surface of an imaging device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,   deriving information about the sample from the imaging device with high spatial resolution using light, and   inspecting the sample using a scanning probe microscope,   the inspecting by the scanning probe microscope being aided by the information derived from the imaging device.   
     
     
         54 . The method of  claim 53  in which positioning of the scanning probe relative to the sample is aided by the information derived from the imaging device.