Patent Publication Number: US-2016231548-A1

Title: Compact microscope apparatus and method of use

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Pat. No. 62,113,679, filed Feb. 9, 2015, entitled “COMPACT MICROSCOPE APPARATUS AND METHOD OF USE,” the contents of which are incorporated herein by reference in their entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates generally to microscopy, and more particularly, to compact microscopes suitable for use in moving or space applications. 
     BACKGROUND OF THE INVENTION 
     Conventional microscopes incorporate large, bulky components. They may be table-top apparatus with external, unattached power sources or control devices. Additionally, conventional microscopes require a stable-unmoving base on which the sample can be positioned in order to obtain a clear, focused microscopic image. 
     Recently, there has been growing interest in the number and diversity of scientific measurements and experiments that may be performed in zero gravity or near-zero gravity environments, such as low earth orbit. Because of the cost and difficulty involved in launching crafts into orbit, any experimental equipment on such crafts is desirably small and lightweight. In view of the above, improved microscope apparatus for use in space and other moving applications are desired. 
     SUMMARY OF THE INVENTION 
     Aspects of the present invention are directed to compact microscope apparatus and methods of use. 
     In accordance with one aspect of the present invention, a compact microscope apparatus is disclosed. The apparatus includes a stage, a light source, an objective, a dichroic element, and an imaging sensor. The stage is configured to hold a sample thereon. The light source is configured to emit light toward the stage. The objective is positioned to focus light from the stage. The dichroic element is configured to pass one of the light emitted by the light source and the light from the stage and reflect the other one of the light emitted by the light source and the light from the stage. The imaging sensor is positioned to receive the light from the stage. The stage, the light source, the objective, the dichroic element, and the imaging sensor are arranged such that they may be received within an enclosure having dimensions no longer than about 300 mm. 
     In accordance with another aspect of the present invention, another compact microscope apparatus is disclosed. The apparatus includes a stage, a light source, an objective, a dichroic element, an imaging sensor, and a clinostat. The stage is configured to hold a sample thereon. The light source is configured to emit light toward the stage. The objective is positioned to focus light from the stage. The dichroic element is configured to pass one of the light emitted by the light source and the light from the stage and reflect the other one of the light emitted by the light source and the light from the stage. The imaging sensor is positioned to receive the light from the stage. The clinostat, to which the stage, the light source, the objective, the dichroic element, and the imaging sensor are attached, is operable to continuously rotate the stage, the light source, the objective, the dichroic element, and the imaging sensor about an axis. 
     In accordance with yet aspect of the present invention, a method for obtaining a microscopic image of a sample is disclosed. The method includes the steps of rotating a microscope with a clinostat, and obtaining an image of the sample with the microscope while the microscope is rotated with the clinostat. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention is best understood from the following detailed description when read in connection with the accompanying drawings, with like elements having the same reference numerals. When a plurality of similar elements are present, a single reference numeral may be assigned to the plurality of similar elements with a small letter designation referring to specific elements. When referring to the elements collectively or to a non-specific one or more of the elements, the small letter designation may be dropped. This emphasizes that according to common practice, the various features of the drawings are not drawn to scale unless otherwise indicated. On the contrary, the dimensions of the various features may be expanded or reduced for clarity. Included in the drawings are the following figures: 
         FIGS. 1A  is a diagram schematically illustrating a layout of an optical subsystem of an exemplary compact microscope apparatus in accordance with aspects of the present invention; 
         FIG. 1B  is a diagram illustrating a side view of the compact microscope apparatus of  FIG. 1A   
         FIG. 2  is a block diagram illustrating an exemplary control structure for the compact microscope apparatus of  FIG. 1A ; 
         FIG. 3  is a diagram illustrating an enclosure of the compact microscope apparatus of  FIG. 1A ; 
         FIGS. 4A-4C  are diagrams illustrating alternative exemplary layouts of the compact microscope apparatus of  FIG. 1A ; 
         FIG. 5  is an image illustrating another exemplary compact microscope apparatus in accordance with aspects of the present invention; and 
         FIG. 6  is a flowchart illustrating an exemplary method for obtaining a microscopic image in accordance with aspects of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The apparatus and methods described herein are directed to compact microscopes that may be used in any application in which a small, lightweight, and/or hermetically-sealed microscope is desired. These exemplary embodiments are described herein principally with respect to fluorescence microscopes. However, it will be understood by one of ordinary skill in the art that the apparatus and methods disclosed herein are usable with any type of microscope known to one of ordinary skill in the art, and are not limited to fluorescence microscopes. Other suitable types of microscopes include, by way of example, wide-field, scattering, phase contrast, dark field and polarization microscopes. 
     The exemplary apparatus and methods disclosed herein may be particularly suitable for enabling microscopy in zero gravity or microgravity environment, such as in orbit. Due to the compact size and low weight of the disclosed microscopes, they are well-suited for use in satellites or other spacecraft where payload weight and size are critical. These disclosed embodiments may enabled the novel testing of microscopic objects in diminished gravity. Likewise, the disclosed embodiments may be useful in any situation where an easily portable microscope may be desired. 
     Conventional microscopes are generally classified as “upright” (i.e. objective facing down on the sample) or “inverted” (objective is below the sample). Inverted microscopes may be used for imaging in liquids because the scope images through the coverslip and into the liquid; conversely, upright microscopes may be more desirable for certain applications of microscopy through air. Due to their small size, the disclosed microscopes may be operated in either upright or inverted configurations (or any other arbitrary configuration), making them preferable to the conventional models that are limited to one or the other. 
     The following description relates generally to compact, portable, high-resolution fluorescence microscopes. The microscope apparatus may be battery operated, and can include computers and cameras. Conventional microscopes are typically stationary, and placed on a stable platform. By contrast, the disclosed embodiments enable use of a compact microscope in applications that require micrographs be obtained while in motion. For example, for a microscope housed in a satellite, the satellite moves about 15,000 miles per hour. Another example is a clinostat microscope that rotates between slightly greater than 0 revolutions per minute (rpm), to over 100 rpm. In a satellite platform, the microscope may be sealed in a hermetic enclosure. Alternatively, the hermetic enclosure may be used in ground-based applications (e.g., where different pressures or gas concentrations (H 2 , N 2 , CO 2 , O 2 ) are used). 
     With reference to the drawings,  FIGS. 1A and 18  illustrate an exemplary compact microscope apparatus  100  in accordance with aspects of the present invention. Apparatus  100  may be a fluorescence microscope usable to obtain microscopic images in low gravity or moving environments. In general, apparatus  100  includes a stage  110 , a light source  120 , an objective  130 , a dichroic element  140 , and an imaging sensor  150 . Additional details of apparatus  100  are described below. 
     Stage  110  is configured to hold a sample thereon. Stage  110  includes a front surface  112  facing objective  130  on which the sample can be mounted. In an exemplary embodiment, stage  110  includes one or more magnets for securing the sample on front surface  112 . The magnets on stage  110  may be positioned to mate with corresponding magnets on a separate plate, such as an aluminum plate. The sample may be provided on the separate plate, or the plate may secure the sample to stage  110  by pressing the sample between the plate and surface  112 . In an alternative embodiment, stage  110  includes one or more attachment structures for securing the sample to stage  110 . Suitable attachment structures will be known to one of ordinary skill in the art, and include, by way of example, clips or clamps. 
     Stage  110  is movable relative to the other components of apparatus  100 . In particular, stage  110  may be movable in a direction along the viewing axis of apparatus  100 , in order to change a distance travelled by light from stage  110  to imaging sensor  150 . In other words, stage  110  is movable to change the focal distance of apparatus  100 . 
     Stage  110  may also include a fluorescent background portion positioned behind the area to which the sample is mounted. The background portion enables microscopic imaging of non-fluorescent samples by effectively back-lighting the samples, creating a pseudo-bright-field image. Suitable background portions include, for example, autofluorescent slides provided by Chroma Technologies Corp., of Bellows Falls, Vt. 
     In an exemplary embodiment, stage  110  includes three piezoelectric-motor driven linear translation stages  116  to form a three-axis sample stage. Each linear translation stage  116  has an integrated linear encoder and approximately 27 mm of travel. Accordingly, stage  110  provides a maximum scan volume of 27×27×14 mm, with a desired minimum step size of about 200 nm. Suitable linear translation stages  116  for use with stage  110  include, by way of example, the Conex-AG-LS25-27P provided by Newport Co. of Irvine, Calif. 
     Each linear translation stage  116  has an associated driver  118  (shown as “controller” in  FIG. 2 ). In an exemplary embodiment, three compact, USB-connected, low-power drivers  118  respectively control the three stages. Each driver may use a serial-via-USB interface to communicate with a computing element  170  for controlling the positioning of stage  110 , as will be discussed below. 
     Light source  120  is configured to emit light toward stage  110 . Light source  120  is selected to emit light at an appropriate excitation wavelength for inducing fluorescence in a sample attached to stage  110 . Alternatively or additionally, light source  120  may be selected to emit light at an appropriate excitation wavelength for inducing fluorescence in the background portion of stage  110  in order to obtain a backlit image of the sample. In an exemplary embodiment, light source  120  is a blue light emitting diode (LED) having a wavelength of around 470 nm. In this embodiment, light source  120  may include a focusing lens, diffuser, and color filter or polarizer, as schematically shown by elements c, d, and e in  FIG. 1A . Suitable components for the above structures will be known to one of ordinary skill in the art from the description herein. Other suitable light sources for use as light source  120  will be known to one of ordinary skill in the art from the description herein. 
     In an exemplary embodiment, a microcontroller  122  (shown in  FIG. 2 ) may be provided to generate a pulse-width-modulated signal for controlling light source  120 . As will be discussed below, microcontroller  122  may be connected to computing element  170  for controlling illumination of the sample with the light source  120 . Suitable microcontrollers for use with light source  120  include, for example, the Arduino Nano provided by Arduino. 
     Objective  130  is positioned to focus light from stage  110 . Objective  130  includes one or more lenses therein to collect and magnify the light from the sample on stage  110 , and transmit that light toward imaging sensor  150 . Suitable objectives for use as objective  130  will be known to one of ordinary skill in the art from the description herein. For example, suitable objectives may be CFI S Plan Fluor ELWD series objectives provided by Nikon Instruments Inc., of Melville, N.Y. The magnification of the objective may be selected based on the desired imaging resolution. Exemplary suitable magnifications for the objectives of the present invention have a magnification of between 1x and 50x, but are not limited thereto. 
     In an exemplary embodiment, objective  130  is not movable relative to the other components of apparatus  100 . Objective  130  may instead be fixed in position relative to image sensor  150 , in order to prevent movement in a direction along the viewing axis of apparatus  100 . In this embodiment, stage  110 , and not objective  130 , is moved in order to change a distance travelled by light from stage  110  to imaging sensor  150 . 
     Apparatus  100  may also include an additional lens  135  positioned between objective  130  and dichroic element  140 , as shown in  FIG. 1A . In an exemplary embodiment, lens  135  is an achromatic lens positioned to act as a tube lens for the microscope. Lens  135  helps focus the excitation light from light source  120  onto the back aperture of objective  130 . Given the space constraints for apparatus  100 , the focal length of lens  135  may be shorter than that nominally required by the objective  130 . Accordingly, the total magnification of the microscope may be modified by a factor of the nominal magnification of objective  130  multiplied by the focal length of lens  135  divided by the normal tube lens focal length: Mag=(Nom. Obj. Mag.)×(Lens  135 )/(Nom. Tube lens). Generally, the higher the numerical aperture (NA), the higher the resolution. Accordingly, using a 60x objective with a shorter-than-design tube lens can offer higher resolution than using an equivalent 20x objective with a lower NA compared to the 60x (e.g. 20X NA .45 objective with nominal 200 mm focal length tube lens will be LOWER resolution than using a 60X NA .75 objective with a 66.6 mm tube lens (mag=20x)). 
     In an exemplary embodiment, objective  130  has a focal length of 200 mm, and lens  135  has a focal length of 125 mm. In apparatus  100 , the focal length of lens  135  is less than that specified for use with most commercial objectives. As a result, the effective magnification this microscope is less than the nominal magnification stamped on the objective (e.g., 12x effective magnification for a 20x objective). 
     Dichroic element  140  redirects light within apparatus  100 . Dichroic element  140  is positioned with the path of the light from light source  120  and the light from stage  110  collected by objective  130 . Dichroic element  140  is a dichroic mirror configured to reflect light falling within a first wavelength band and to allow light falling within a second different wavelength band to be transmitted therethrough. Dichroic element  140  may have a reflective coating formed on one side thereof, in order to assist in reflecting incoming light received from one direction, and transmit incoming light from an opposite direction. 
     In an exemplary embodiment, dichroic element  140  is designed to allow light from light source  120  to pass therethrough, and to reflect light from stage  110  toward imaging sensor  150 . This configuration may be desirable in order to minimize the size of apparatus  100 , as will be discussed below. Alternatively, dichroic element  140  may be designed to allow light from stage  110  to pass therethrough, and to reflect light from light source  120 . In an exemplary embodiment, dichroic element  140  is a dichroic mirror provided by Chroma Technologies Corp, of Bellows Falls, Vt. This dichroic mirror may be configured to transmit light in a wavelength band of 400 to 490 nm and to reflect light in a wavelength band of 500 to 830 nm. 
     Apparatus  100  may also include one or more additional mirrors  145  for redirecting the light from dichroic element  140  toward the imaging sensor  150 . Likewise, apparatus  100  may include an aperture and a color filter between dichroic element  140  and mirror  145 , as schematically shown as elements g and h in  FIG. 1A . 
     Imaging sensor  150  is positioned to receive light from stage  110  redirected by dichroic element  140 . Imaging sensor  150  is configured to record an image of the sample on stage  110 . In an exemplary embodiment, imaging sensor  150  is a charge-coupled device (CCD) image sensor. Suitable CCD image sensors for use as imaging sensor  150  include, for example, the PCO.Pixelfly USB, provided by PCO AG, Kelheim, Germany. Other suitable image sensors will be known to one of ordinary skill in the art from the description herein, and may include CMOS image sensors. 
     The above-recited components of microscope apparatus  100  are selected and arranged in such a manner to provide a compact total package for the apparatus  100 . The arrangement of the components of apparatus  100  may be selected based on the space or volume requirements of the particular application in which apparatus  100  will be used. 
     In an exemplary embodiment, apparatus  100  may be designated for use as a microscope on a satellite or other spacecraft. In this embodiment, the components of apparatus  100  are arranged such that they will fit within an enclosure having dimensions no longer than about 300 mm (e.g., a cube having 300 mm edges). Preferably, the components of apparatus  100  are arranged such that they will fit within an enclosure having dimensions no longer than about 300 mm by about 100 mm by about 100 mm. Even more preferably, the components of apparatus 100 are arranged such that they will fit within an enclosure having dimensions of about 200 mm by about 100 mm by about 100 mm. An exemplary arrangement of the components of apparatus  100  is shown in  FIGS. 1A and 1B . 
     The above-described dimensions may be particularly desirable for utilization of the disclosed microscope apparatus in pre-existing compartments of conventional miniaturized satellites known as CubeSat satellites. CubeSat satellites typically have cubical compartments measuring 100 mm on a side, and may be coupled together to create longer compartments along a single dimension (e.g., 200×100×100, 300×100×100, etc.). An apparatus fitting within an enclosure having dimensions of about 200 mm by about 100 mm by about 100 mm may be usable in a “2U” CubeSat, or a “3U” CubeSat if external components are required. 
     In any enclosure, it may be necessary for the components to be sufficiently smaller to provide space for the walls of the enclosure. In an exemplary embodiment, the enclosure will have walls having a thickness of about 3 mm, meaning that for an enclosure 100 mm wide, the components of the microscope may have a corresponding dimension of no more than about 94 mm. 
     It will be understood that the above-described dimensions for apparatus  100  are provided in view of the exemplary application recited above, and are not intended to be limiting. Alternative dimensions or shapes for the arrangement of components of apparatus  100  will be apparent to one of ordinary skill in the art from the description herein and the intended use of apparatus  100 . 
     Additionally, the above-recited components of microscope apparatus  100  are selected to provide a lightweight total apparatus  100 . In an exemplary embodiment, apparatus  100  has a mass of no more than 5 kg. Preferably, apparatus  100  has a mass of about 2.5 kg without its associated enclosure, and a mass of about 4.5 kg with an associated aluminum hermetic enclosure. It is desirable that apparatus have such a mass to ensure that it suitable for use in applications requiring an easily portable or movable microscope. Likewise, it is desirable that apparatus  100  have relatively low power requirements, to ensure that it can be operated in orbital environments where power availability may be limited. In an exemplary embodiment, apparatus  100  has an average power consumption of less than approximately 60 J per image obtained by imaging sensor  150  (or less than approximately 0.02 Whr). This energy may be utilized to move the stage  110  a predetermined distance (e.g., 1 mm), turn on light source  120 , acquire an image with imaging sensor  150 , turn off light source  120 , compress the image using an onboard computing element, and store the image. To this end, exemplary components having low power consumption are disclosed herein, and will otherwise be known to one of ordinary skill in the art from the description herein. 
     Apparatus  100  is not limited to the above-described components, but may include alternative or additional components, as would be understood by one of ordinary skill in the art in view of the description herein. 
     For example, apparatus  100  may include a power supply. The power supply is coupled to provide power to the components of apparatus  100 , including light source  120  and imaging sensor  150 . In an exemplary embodiment, the power source is an on-board battery, such as a conventional 12 volt battery. Alternatively, apparatus  100  may include a connector  160  for attachment to an external power source. In such an embodiment, apparatus  100  may include an adaptor for adapting the power from the external power source (e.g., AC power) to a desired form for use by the components of apparatus  100 . It may be preferable that apparatus  100  include an on-board power source in order to achieve the desired portability of apparatus  100 . 
     For another example, apparatus  100  may include a computing element  170 . Computing element  170  may be coupled to light source  120  and/or imaging sensor  150 . Computing element  170  may be operable to provide instructions for turning light source  120  on or off. Computing element  170  may also be operable to provide instructions to imaging sensor  150  to obtain images of the sample when the sample is held on stage  110 . In an exemplary embodiment, computing element  170  is a Raspberry Pi Model B single-board-computer provided by the Raspberry Pi Foundation, Caldecote, Cambridgeshire, UK. Other suitable computing elements will be known to one of ordinary skill in the art from the description herein. 
     In order to achieve the desired low power consumption of apparatus  100 , computing element  170  can be placed in a low power standby state for brief intervals. For example, where data collection is infrequent (e.g., 1-10 data sets per 24 hr), the whole electronic system of apparatus  100  can be shut down, and rebooted at predefined intervals via an onboard real-time clock. 
     Computing element  170  may also be configured to communicate with devices external to apparatus  100 . Communication with external devices may be desirable to allow apparatus  100  to be operated from a remote location, or to allow remote viewing and storage of the images obtained by apparatus  100 . Such communication may be wired communication or wireless communication. In one embodiment, computing element  170  is in communication with at least one connector  160 . Connector  160  may enable serial or parallel communication with an external computer when a wire is connected thereto. In an alternative embodiment, computing element  170  includes one or more wireless transceivers for enabling wireless communication with an external computer. For example, a Bluetooth transceiver may be used to create a wireless connection to a nearby smartphone or computer, or an IEEE 802.11 compliant wireless transceiver may be used to connect computing element  170  to a local area network. Either may allow data and command transfer between the computing element  170  and a remote computer. 
     For yet another example, apparatus  100  may include a memory device. The memory device may be coupled to computing element  170  and imaging sensor  150 , such that computing element is operable to provide instructions for the memory device to store the images of the sample obtained by imaging sensor  150 . Computing element  170  is desirably capable of acquiring, compressing, and storing a 16-bit, 1392×1040 pixel image to the memory device at a rate of at least approximately 0.5 frames per second. Preferably, computing element  170  is operable to acquire, compress, and store images at rates up to 60 fps, depending on the design and speed of computing element  170 . In an exemplary embodiment, the memory device is a conventional memory card, such as a Secured Digital (SD) non-volatile memory card. Other suitable memory devices will be known to one of ordinary skill in the art from the description herein. 
     Where apparatus  100  includes any of the additional components recited above, or any other additional components, it will be understood that these additional components must also be arranged to achieve the spatial requirements determined for the application of apparatus  100 . In other words, the power source, computing element  170 , and the memory device, when present, must also be arranged to fit within the same dimensions as the remaining components of apparatus  100 . 
       FIG. 2  illustrates an exemplary control structure for microscope apparatus  100 . In an exemplary embodiment, computing element  170  is coupled to the components of apparatus  100  by way of a conventional USB hub  174 . USB hub  174  provides connections between computing element  170  and the stage drivers  118 , the light source microcontroller  122 , and imaging sensor  150 . USB hub may also include connections for providing power to the components of apparatus  100  such as light source  120  and imaging sensor  150 . Computing element  170  may thereby communicate with these components via USB communications protocol. Computing element  170  may thereby instruct drivers  118  to adjust the position of stage  110 , may instruct microcontroller  122  to turn on or off light source  120 , or may instruct imaging sensor  150  to acquire images of the sample. 
     Apparatus  100  may also include an enclosure  190 , as shown in  FIG. 3 . As with the arrangement of components of apparatus  100 , the dimensions of enclosure  190  are selected based on the space or volume requirements of the particular application in which apparatus  100  will be used. In an exemplary embodiment, enclosure  190  has dimensions no longer than about 300 mm on any side. Preferably, enclosure has dimensions no longer than about 200 mm on any side. Even more preferably, enclosure  190  has dimensions of about 200 mm by about 100 mm by about 100 mm. 
     Enclosure  190  may be hermetically-sealed. This may be preferable for applications in which apparatus  100  is designated for use as a microscope on a satellite or other spacecraft. Suitable structures or materials for hermetically sealing enclosure  190  will be known to one of ordinary skill in the art from the description herein. A hermetic enclosure  190  may be useful in order to change the atmospheric pressure, gas composition, etc., therein, in order to keep samples in a controlled and defined environment. The hermetic enclosure  190  may further include one or more heaters and/or coolers in order to regulate the temp of both the components and the sample. 
     In an exemplary embodiment, the optical and electronic components of apparatus  100  are assembled on a system of shelves or trays with enclosure  190 , as shown in  FIG. 18 . These shelves may be designed to slide into rails in enclosure  190 . Separating the optical and electronic components into layers may facilitate assembly and wiring. 
     In accordance with aspects of the present invention, systems may be formed including multiple microscope apparatus  100 . In an exemplary embodiment, a system may be formed including one or more microscopes of varying types. For example, an exemplary system may include one or more of a fluorescence microscope, a dark field microscope, and/or a chemiluminescent microscope. The selection of light sources and stages for these other microscope types will be known to one of ordinary skill in the art from the description herein. 
       FIGS. 4A-4C  show alternative exemplary layouts of the microscope components of apparatus  100 . These embodiments may be well-suited for creating a desired travel length of light from the stage to the imaging sensor in order to form an image using the objective, while maintaining a compact arrangement of components. In an exemplary embodiment, a path length of up to 200 mm can be created by two or more beam folding mirrors, as shown in  FIGS. 4A-4C . If more space is needed for electronic components of the microscope, then additional mirrors may be used in a 3D configuration to fit the optical components. 
       FIG. 4A  illustrates an optical layout for a 3U CubeSat enclosure, having dimensions of about 300 mm by about 100 mm by about 100 mm.  FIGS. 4B and 4C  illustrate an optical layout for a 2U CubeSat enclosure, having dimensions of about 200 mm by about 100 mm by about 100 mm. The basic microscope configurations are based on epiillumination. In  FIG. 4A , the light source is a blue LED that is collimated by lenses L 1  and L 2 . M 1  is a mirror that diverts the light to reflect off a dichroic mirror (M 2 ) and projected onto the back aperture of a 50x air objective. The illumination light is focused onto the sample (in this example, a microfluidic device or “worm chip” housing living microorganisms). The reflected light (or fluorescence) is passed through M 2  and focused by a 200 mm tube lens (TL). The focused light is directed by three mirrors (M 3 , M 4 , M 5 ) to a CCD camera (gray boxes). A movable bandpass filter can be placed before the CCD to collect only the emitted fluorescence. In  FIGS. 4B and 4C , the microscope design is similar to the 2D optical layout from  FIG. 4A , except that the illumination and image path is steered in three dimensions to improve space efficiency.  FIG. 4B  is the front view of the instrument, and  FIG. 4C  is the side view. M 6  is a small mirror that can be used with ultra long working distance objectives (˜20 mm) to further optimize space. 
       FIG. 5  illustrates another exemplary compact microscope apparatus  200  in accordance with aspects of the present invention. Apparatus  200  may be a fluorescence microscope usable to obtain microscopic images in low gravity or moving environments. Apparatus  200  includes the same components as apparatus  100  except as indicated below. 
     Apparatus  200  includes a clinostat  250 . Clinostat  250  is a device configured to continuously rotate one or more objects (e.g. mounted to a disc) in order to negate the effects of gravity on the objects. In an exemplary embodiment, clinostat  250  includes a frame or disc and a pulley that connects the frame or disc to a motor. This motor is geared to provide stable rotation speeds in the range 1-20 rpm. Suitable motors for use in clinostat  250  include, for example, brushless DC motors provided by www.wondermotor.com. 
     The stage, light source, objective, dichroic element, and image sensor of apparatus  200  (hereinafter the “microscope components  210 ”) are coupled to the disc of clinostat  250 . As such, clinostat  250  is operable to continuously rotate the microscope components  210  of apparatus  200  about an axis. The axis may be oriented in a direction perpendicular to the focal plane of the stage. 
     Rotating the microscope components  210  with clinostat  250  may introduce mechanical noise into the imaging system, primarily as a cyclic shift in the image field-of-view. This shift can be caused by slight shifts in the body of the microscope components  210  at different angles relative to the gravitational field. This can be compensated for by either using fiducial markers—for example, by placing sample on micro-ruled coverslips—or by synchronizing the imaging system with the rotating frame. 
     Clinostat  250  may include its own power source, or may share a power source with the microscope components  210  of apparatus  200 . Where clinostat  250  shares a power source with the microscope components  210 , or where the microscope components  210  are coupled to an external power supply, apparatus  200  may include one or more electrical slip rings. An electrical slip ring includes a continuous annular electrical contact, which may be contacted by a rotating electrical contact throughout its rotation to maintain electrical contact between the rotating contact and the stationary annular contact. An exemplary slip ring  270  for coupling the microscope components  210  of apparatus  200  to an external power source is shown in  FIG. 5 . Suitable slip rings for use as slip ring  270  include, for example, those provided by Adafruit Industries, of New York, N.Y. 
     Clinostat  250  may also include its own computing element, or may share a computing element with the microscope components  210  of apparatus  200 . The computing element of clinostat  250  may be operable to provide instructions for turning on and off the rotation of clinostat  250 . The computing element may also control a rotational speed of clinostat  250 , e.g., through pulse-width modulated control signals. 
     As with apparatus  100 , the microscope components  210  of apparatus  200  may be sized and arranged to be enclosed within an enclosure. The enclosure of apparatus  200  may have the same or different dimensions and features from the enclosure  190  of apparatus  100 . In an exemplary embodiment, the enclosure of apparatus  200  may enclose only the microscope components  210 . In this embodiment, the enclosure itself may be mounted to the disc of clinostat  250 . Alternatively, apparatus  200  may include an enclosure that encloses both the microscope components  210  and clinostat  250 . 
       FIG. 6  illustrates an exemplary method  300  for obtaining a microscopic image in accordance with aspects of the present invention. Method  300  may be used to obtain microscopic images in low gravity or moving environments. As a general overview, method  300  includes the steps of rotating a microscope with a clinostat, and obtaining an image of a sample with the rotating microscope. Additional details of method  300  are described below. 
     In step  310 , a microscope is rotated with a clinostat. In an exemplary embodiment, the microscope components  210  of apparatus  200  are rotated using clinostat  250 . The microscope components  210  may be continuously rotated over a period of time selected based on a desired length of observation of the sample. Suitable periods of rotation include, for example, 1-20 rpm. 
     In step  320 , an image of a sample is obtained. In an exemplary embodiment, the imaging sensor obtains a microscopic image of a sample on the stage during rotation of the microscope components  210  by clinostat  250 . The imaging sensor may continuously obtain images, or may periodically obtain images during rotation. 
     Method  300  is not limited to the above-described steps, but may include alternate or additional steps, as would be understood by one of ordinary skill in the art from the description herein. 
     For example, where apparatus  200  includes an enclosure, method  300  may include the step of enclosing the components of apparatus  200  within the enclosure. The microscope components  210  of apparatus  200  may be enclosed, or alternatively, the microscope components  210  and clinostat  250  may be enclosed, depending on the intended use of apparatus  200 . 
     For another example, method  300  may include the step of changing a distance travelled by the light from the stage to the imaging sensor. As set forth above, the stage of the microscope may be movable to change the focal distance of the microscope. By moving the stage, the distance travelled by the light may be changed in order to focus the microscope on the sample to be imaged. 
     Although the invention is illustrated and described herein with reference to specific embodiments, the invention is not intended to be limited to the details shown. Rather, various modifications may be made in the details within the scope and range of equivalents of the claims and without departing from the invention.