Patent Publication Number: US-11660617-B2

Title: Thermal regulation of rotors during centrifugation

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
     The present application is a US National Phase of PCT Application No. PCT/US2017/051400 filed on Sep. 13, 2017, which claims priority to US Provisional Application No. 62/395,261, filed Sep. 15, 2016, the entireties of which are incorporated herein by reference for all purposes. 
     BACKGROUND OF THE INVENTION 
     A centrifuge is commonly used to separate substances in a sample by subjecting the sample to a centrifugal force. The centrifugal force is generated by spinning a rotor containing the sample at a selected speed. Substances separate based on differences in size, weight, or density, as larger, heavier, more dense substances sediment faster in response to the centrifugal force. For example, centrifugation is used to separate solid materials that precipitate out of a liquid solution, or to form a density gradient to separate molecules based on size and density. 
     For some high-speed centrifuges, such as ultracentrifuges, the centrifuge chamber is a vacuum chamber. The air in the centrifuge chamber is evacuated during centrifugation to maintain a constant, low air pressure. This reduced pressure decreases frictional heating of the rotor caused by air molecules in the chamber that strike the rotor as it spins. 
     In an analytical ultracentrifuge, physical characteristics of a particle, such as molecular weight, can be calculated based on a determined rate of sedimentation of the particle during centrifugation. The rate of sedimentation is determined by monitoring the position of the particle along the radial length (i.e. along the axis of the centrifugal force) of a sample cell containing the sample during centrifugation. The sample cell includes a window on the top and the bottom so that the sample, and particles therein, can be observed during centrifugation. The position of the particle is detected by changes in absorbance, interference, or fluorescence along the radial length of the sample cell. To detect these changes, the analytical ultracentrifuge has an analytical module including a light source, a detector, and an optical element. The light source and optical element are configured to deliver an illuminating beam of light to the window of the sample cell and the detector is configured to measure the amount or pattern of the illuminated light after the light passes through the sample through the windows of the sample cell. 
     To provide the illuminating beam of light, analytical ultracentrifuges of the prior art comprise an illuminating optical subsystem including a light source and beam shaping/steering optics positioned inside the centrifuge chamber. It is desirable that components of the illuminating optical subsystem be maintained in precise alignment to provide an accurate and precise measure of particle position during centrifugation. However, because the illuminating optical subsystem is positioned inside the centrifuge chamber, it is subject to the varying temperature and pressure conditions inside the centrifuge chamber. Temperature changes can cause variation in position of the components induced by thermal expansion or contraction, thus causing optical misalignment. Reduced temperatures can cause condensation on optical surfaces, reducing the effectiveness or performance of optical components. 
     One prior art analytical ultracentrifuge keeps all components of the illumination optical subsystem and the detection subsystem outside the centrifuge chamber. At least a portion of the illumination optical subsystem is positioned above the centrifuge chamber, and the detection module is positioned below the centrifuge chamber. A window in the top wall of the chamber allows the illuminating light to shine onto the sample through the top of the rotor, and a window in the bottom wall of the chamber allows the light emanating from the sample to reach the detector. The positioning of at least a portion of the illuminating optical subsystem above the rotor can interfere with a user&#39;s access to the rotor, such as blocking the insertion or removal of the rotor. 
     In many cases, the sample processed by a centrifuge is a biological sample. Typically, these samples are maintained at a constant temperature below ambient to preserve the molecular structure or biological activity of the sample. Typically, the biological sample is maintained at a refrigerated temperature of approximately 0° to 40° C. To maintain a refrigerated temperature of a sample during centrifugation, the rotor containing the sample centrifugation is usually cooled or heated. 
     In some prior art systems, the rotor is cooled indirectly by cooling a wall of the centrifuge chamber containing the rotor as it spins. The cooled wall maintains a reduced temperature inside the entire centrifuge chamber, thereby indirectly cooling the rotor as it spins inside the chamber. For example, in some prior art systems, the wall of the centrifuge chamber can be cooled by a thermoelectric element placed in direct contact with the wall on the outside of the centrifuge chamber. Alternatively, coils containing a circulating coolant fluid can be placed in direct contact with the wall on the outside of the centrifuge chamber. The cooled wall can be a side wall or the floor of the centrifuge chamber. The temperature of the wall is controlled by adjusting the electrical current delivered to the thermoelectric element or by controlling the temperature of the circulating coolant fluid as is common in refrigeration systems. Because the entire chamber is typically cooled, these systems can be inefficient, requiring higher energy and a longer time to cool a rotor compared to a system that locally cools the rotor by positioning a cooling surface in close proximity to the rotor. In addition, the temperature accuracy required for an analytical ultracentrifuge is very difficult to achieve with a refrigeration-based system cooling a rotor via cooling coils in the chamber walls. Another disadvantage of systems that control the temperature of the wall of the centrifuge in order to control the temperature of the rotor inside the chamber is that the entire chamber is cooled to the same temperature. This can have deleterious effects on other components inside the centrifuge chamber, such as delicate optical components of an analytical ultracentrifuge. 
     Prior art analytical ultracentrifuges with a thermoelectric element in direct contact with the floor of the centrifuge include a heat sink directly coupled to the thermoelectric element to dissipate the heat absorbed from the wall and components such as the rotor of the centrifuge floor and the heat generated by the by the thermoelectric element itself. A fan typically blows air over the cooling fins of the heat sink to transfer the absorbed heat to outside the body or housing of the centrifuge. Because the heat sink is directly coupled to the thermoelectric device attached to the floor of the centrifuge chamber, the heat sink is positioned below the floor of the centrifuge chamber. The heat sink thus takes up space beneath the floor of the centrifuge chamber that could otherwise be used to house other components of the centrifuge. In particular, the heat sinks take-up space that could otherwise be used for components of the illuminating optical subsystem of an analytical ultracentrifuge, such as the light source. 
     Another prior art system comprises a thermoelectric device directly coupled to the rotor to control the temperature of the rotor as it spins in the chamber. This arrangement has the disadvantage that the thermoelectric device becomes a moving part that rotates with the rotor, and is thus more complex than a cooling element that remains stationary inside the centrifugation chamber. 
     What is needed is a temperature regulation system to cool or heat a spinning rotor in a centrifuge chamber that is more efficient, requires less energy, and is less complex than prior art systems. Ideally such a temperature control element is compatible with a vacuum chamber and minimizes changes in position or alignment of optical and/or electromechanical components inside the centrifuge chamber as the rotor spins and changes its temperature from the temperature at which the optical components are aligned and optimized. The optical alignment is typically performed at a controlled room temperature What is further needed is a temperature regulation system in an analytical ultracentrifuge that preserves space beneath the centrifuge chamber for illumination and/or detection components of the analytical module(s). The present invention addresses these and other needs. 
     BRIEF SUMMARY OF THE INVENTION 
     The present invention provides a centrifuge (e.g., an analytical centrifuge) comprising a centrifuge chamber including a chamber wall; a rotor disposed in the centrifuge chamber, the rotor arranged to spin in the centrifuge chamber; and a thermal module (in some embodiments, a cooling assembly) including a transfer surface (in some embodiments, a cooling surface) and a thermal element, the cooling surface disposed inside the centrifuge chamber, spaced apart from the rotor, and configured to exchange heat between the cooling assembly and the rotor, the thermal element thermally coupled to the cooling surface, and configured to control the temperature of the cooling surface. In some embodiments, the thermal element is a thermoelectric device. The transfer surface can be a cooling surface or a heating surface to cool or heat the rotor, respectively. In some embodiments, the thermal module includes a transfer plate and the transfer surface is on the transfer plate. The chamber may comprise a plurality of cooling assemblies. A plurality of cooling surfaces can be positioned together to define a thermal compartment around the rotor. Alternatively, multiple cooling assemblies can share a single cooling surface represented by a single piece of hardware. 
     In particular, the invention provides a centrifuge comprising: a rotor including a rotor surface, a centrifuge chamber configured to enclose the rotor, and one or more cooling surfaces to absorb heat from the rotor surface. The cooling surface(s) are disposed inside the centrifuge chamber and arranged facing and spaced-apart from the rotor surface. The cooling surface(s) are sized to cover at least a portion of the perimeter of the rotor surface. The portion of the perimeter covered by the cooling surface(s) can be a segment of the perimeter. In some embodiments, the cooling surface(s) surrounds the rotor. 
     The centrifuges of the invention may comprise one or more thermal elements disposed inside the centrifuge chamber to adjust the temperature of the cooling surface(s). Each thermal element can be reversibly coupled to a cooling surface to allow removal of the cooling surface from the centrifuge chamber. 
     The height of the cooling surface(s) can be selected for any desired configuration. In some embodiments, the height is less than or approximately equal to the height of the rotor. In some embodiments, the height is less than 120% of the height of the rotor. In some embodiments, the height of the cooling surface is much greater than that of the rotor, for example up to 200%, in some embodiments, up to 400% of the height of the rotor. 
     The distance between rotor surface and the cooling surface(s) can also be adjusted. In some embodiments, the cooling surface(s) and the rotor surface have a minimum clearance of less than 15 millimeters. In other embodiments, the minimum clearance is less than 10 millimeters or less than 5 millimeters. 
     The centrifuges of the invention may further comprise a second cooling surface arranged facing and spaced-apart from the rotor surface to absorb heat from the rotor surface. 
     The invention further provides a centrifuge comprising: a rotor including a rotor surface, the rotor configured to hold a sample, a centrifuge chamber configured to enclose the rotor, and a cooling assembly disposed inside the centrifuge chamber. The cooling assembly includes a cooling surface and a thermal element. The cooling surface is arranged spaced-apart and facing the rotor surface to absorb heat from the rotor surface. The thermal element thermally coupled to the cooling surface to adjust the temperature of the cooling surface. 
     The centrifuge may further comprise a heat pipe thermally coupled to the thermal element. The heat pipe is arranged to transfer heat from the thermal element to outside the centrifuge chamber. In some embodiments, a heat sink is disposed outside the centrifuge chamber. The heat sink is thermally coupled to the heat pipe to dissipate the heat transferred from the thermal element. 
     In some embodiment, the rotor includes a window to view the sample and the centrifuge further comprises an optical element disposed inside the centrifuge chamber to deliver a beam of light to the window. In some embodiments, the cooling surface is disposed between the optical element and the rotor surface. The centrifuge may further comprise a light source and a detector disposed outside the centrifuge chamber. The light source is arranged to deliver a beam of light to the optical element, wherein the rotor includes a second window, and wherein the detector is arranged to receive a beam of light emitted through the second window. In some embodiments, the light source and the detector are disposed beneath the chamber floor. 
     The invention further provides a centrifuge comprising: a rotor configured to hold a sample, a drive coupled to the rotor to spin the rotor, and a cooling surface arranged facing and spaced-apart from the rotor to cool the rotor, wherein the minimum clearance between the rotor and the cooling surface is less than 15 millimeters. In some embodiments, the minimum clearance between the rotor and the cooling surface is less than 10 millimeters, in other embodiments, the minimum clearance between the rotor and the cooling surface is less than 5 millimeters. The centrifuge may further comprise a centrifuge chamber configured to enclose the rotor, wherein the cooling surface is disposed inside the centrifuge chamber. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    depicts a side view of a centrifuge chamber of the invention. 
         FIG.  2    depicts a side view of a centrifuge chamber of the invention. 
         FIG.  3 A  depicts a side view and  FIG.  3 B  depicts a top view of a centrifuge chamber of the invention. 
         FIG.  4 A  depicts a side view and  FIG.  4 B  depicts a top view of a centrifuge chamber of the invention. 
         FIG.  5    depicts a side view of a centrifuge chamber of the invention. 
         FIG.  6 A and  6 B  depict a cooling assembly of the invention. 
         FIGS.  7 A, and  7 B , depict a cooling assembly of the invention.  FIG.  7 C  depicts a top view of a centrifuge chamber of the invention. 
         FIG.  8    (including  FIGS.  8 A- 8 K ) depicts different embodiments of rotors and cooling surfaces of the invention.  
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The invention provides centrifuges (e.g., analytical ultracentrifuges) in which the rotor is cooled locally by a cooling surface positioned close to the surface of the rotor and thermally coupled to a thermal element positioned in the centrifuge chamber. This avoids the need to cool the entire centrifuge chamber, thus allowing faster cooling of the rotor with less energy, while minimizing the cooling of other components in the chamber. In the case of analytical ultracentrifuges, the centrifuge chamber can be maintained at a temperature closer to ambient temperature, thus avoiding the problems of subjecting optomechanical components present in the chamber to large changes in temperature. 
     More specifically, placing the cooling surface inside the centrifuge chamber allows the cooling surface to be positioned as close as practical to the rotor surface. This close proximity concentrates the heat transfer to and from the rotor, while at the same time minimizing heat transfer to or from other components in the chamber, such as components of an analytical module. Minimizing heat transfer to or from other components that do not need to be heated or cooled reduces energy consumption. Moreover, minimizing heat transfer to or from other components in the chamber minimizes the deleterious effects of thermal expansion and contraction of those components, such as the misalignment of delicate optical components of an analytical module caused by the thermal expansion or contraction. 
     Furthermore, placing the cooling surface inside the centrifuge chamber, (i.e. separate from the chamber walls) allows the size and shape of the cooling surface to be customized for optimal cooling of the rotor and minimal cooling of other components in the centrifuge chamber. Sizing the cooling surface to cover the height of the rotor, for example, improves the geometric form factor, providing an increased rate of heat transfer. By not extending the cooling surface a significant distance above or beyond the rotor, less energy is wasted, since a cooling surface in such extended segments does not effectively cool the rotor. Moreover, reducing the size of the cooling surface to that which covers the rotor, (i.e. eliminating surfaces that do not cover the rotor), reduces the thermal mass of the cooling surface, providing further reduction in energy consumption. 
     Placing the cooling surface inside the centrifuge chamber is further advantageous because it allows the use of cooling surfaces that are easily replaceable, each cooling surface optimized for a given rotor. This is in contrast to prior art centrifuges that cool the rotor by cooling the centrifuge chamber itself, which is not removable and which is of a fixed size that cannot be optimized for different rotors. 
     The cooling surface may be divided into segments. Using segmented cooling surfaces, where each cooling surface covers only a portion of the rotor, is advantageous because it allows each segment to be placed in close proximity to the rotor at a position optimal for cooling the rotor. Furthermore, the positions of the individual segments can be adjusted to allow for optimal cooling of different-sized rotors. The segmented cooling surfaces also allow for gaps to be placed between adjacent cooling surfaces to allow space for other components, such as those of an analytical module, to be placed about the rotor. 
     The cooling surface may be coupled to a thermal element, such as a thermoelectric device, to adjust the temperature of the cooling surface. Positioning the thermal element inside the centrifuge chamber advantageously facilitates positioning the cooling surface close to the rotor (inside the chamber). Positioning the thermal element inside the centrifuge chamber also allows heat transfer to be limited to the cooling surface, thereby minimizing the energy wasted in cooling other components of the centrifuge, including the walls of the centrifuge chamber. 
     The thermal element, positioned inside the centrifuge chamber, may be coupled to a heat pipe to transfer heat from the thermal element to a location outside the centrifuge chamber. The heat pipe may be coupled to a heat sink positioned outside the centrifuge chamber to dissipate the heat transferred from the thermal element. The use of a heat pipe to transfer heat from the thermal element to the heat sink advantageously allows the heat sink to be positioned at any suitable location outside the centrifuge chamber. Thus, unlike prior art systems, analytical ultracentrifuges of the invention do not limit the positioning of the heat sink to a location under the centrifuge chamber, or to any particular orientation relative to the rotor, which preserves space beneath the centrifuge chamber for optical subsystems (e.g., illumination and/or detection components) of the centrifuge. 
     The standard components of the centrifuges of the invention, including analytical ultracentrifuges, are well known to those of skill in the art and are not described in detail here. The centrifuges will typically comprise a housing, a centrifuge chamber, a rotor, a drive, control elements, and integrated analytical equipment. Control elements can include drive control elements to control the rotation of the rotor and vacuum control elements to control the air pressure inside the centrifuge chamber. The centrifuge can be floor-model or benchtop centrifuge. 
       FIG.  1    shows a side view of a centrifuge chamber  101  in a centrifuge of the invention. The centrifuge chamber  101  forms a containment compartment that encloses the rotor  102  and isolates the rotor from other mechanical components of the centrifuge. The centrifuge chamber comprises side walls  103 , a chamber floor  104  and an upper wall (not shown). The upper wall typically includes a door to allow access to the centrifuge chamber to insert and remove the rotor. In some embodiments, the centrifuge chamber  101  is a sealed, vacuum chamber, where a vacuum source (not shown) is coupled to the centrifuge chamber to reduce the atmospheric pressure inside the chamber during a centrifugation run. For example, the atmospheric pressure inside the centrifuge chamber can be maintained at 1 to 5 micro-meters of mercury during centrifugation. 
     The rotor  102  is configured to hold samples and subject the samples to a centrifugal force by spinning the samples in the centrifuge chamber  101 . In some embodiments, the sample is contained in a tube, and the rotor  102  has cavities to receive the tubes. The cavities can be fixed at a constant angle. In other embodiments, the cavities are allowed to swing into a horizontal position under centrifugal force. The rotor  102  can be made of metal, fiberglass, plastic, or any suitable material that is strong enough to withstand the forces during centrifugation. In some embodiments, the rotor  102  includes a sample cell containing windows on the top and bottom of the sample cell. This allows sedimentation of particles in the sample to be monitored by optical modules in an analytical ultracentrifuge. 
     A drive  105  is coupled to the rotor  102  to cause rotation of the rotor  102  in the centrifuge. In some embodiments, the drive  105  includes a motor and a spindle (not shown). The rotor  102  reversibly mounts onto the spindle; the motor turns the spindle, causing rotation of the rotor  102  mounted on the spindle. The motor can be an induction motor, a DC motor, or any suitable motor. 
     In the embodiment shown in  FIG.  1   , a thermal element  107  is attached to a side wall  103  of the chamber  101 . The thermal element  107  directly controls the temperature of the rotor  102  inside the centrifuge chamber  101 . In some embodiments, the thermal element  107  is coupled to a transfer plate  109  to provide a larger surface area for controlling the temperature of the rotor  102 . The transfer plate  109  includes a cooling surface  108  to absorb heat from the surface of the rotor  102 . In a typical embodiment, cooling surface  108  is functional between a minimum temperature of −20° C. and 60° C. In embodiments in which a transfer plate is not used, the cooling surface  108  is a surface of the thermal element  107 . The cooling surface  108  is typically positioned proximate, but apart from the rotor  102 . Because it is positioned apart from rotor  102 , the cooling surface  108  remains stationary in the centrifuge chamber while the rotor  102  spins. This simplifies the mechanical design, since wires or other coupled components do not have to be attached to an element spinning with the rotor at high RPM. The cooling surface  108  is positioned proximate to the rotor  102  so that heat can be absorbed effectively from the rotor  102  and thereby control the temperature of the rotor  102 , while minimizing temperature changes elsewhere in the centrifuge chamber  101 , including the walls of the centrifuge chamber or sensitive optical or electromechanical components positioned inside the centrifuge chamber. 
     The cooling surface  108  is positioned at a distance from the rotor  102  close enough to provide efficient heat exchange between the cooling surface  108  and the rotor  102 , while maintaining a safe separation from the rotor  102 . For example, the cooling surface  108  can be positioned such that the minimum distance between the rotor  102  and the cooling surface  108  can be less than about 15 millimeters, or less than 10 millimeters, or less than about 5 millimeters. One of skill will recognize that the distance can be selected to maintain a desired temperature behavior of the rotor and that the distance will determine the heat transfer, power and control parameters of the system. 
     One of skill will recognize that, if the exchange of heat is intended to be limited to the rotor and the cooling surface, the gap between the cooling surface and the rotor, along with heat transfer media and the radiation transport properties of the participating surfaces, dictate the rate of heat transfer. An ultracentrifuge is typically operated in a vacuum environment where heat transfer is a function of the temperatures, the properties of the surfaces (e.g., emissivity and absorptivity), and the geometric view factor relationships between the surfaces. The geometric view factor between two surfaces is a measure of the fraction of the thermal radiation emitted by one surface which is intercepted by the other surface. Surface geometric relationships between the cooling surfaces and the rotors of the invention are typically designed to have a high geometric view factor. One implementation of a high geometric view factor is to arrange the cooling surface as close to and over as large a region of the rotor surface as feasible. The minimum gap size is dictated by the mechanical constraints such as runout and wobble of the rotor in order to avoid any collisions between the rotor and the cooling surface. In some embodiments, to optimize the geometric view factor while minimizing the transfer of heat to other components inside the centrifuge chamber, the height of the cooling surface  108  is less than or approximately equal to the height of the rotor  102 . In some embodiments, the height of the cooling surface  108  is less than 120%, or less than 115%, or less than 110%, or less than 105% of the height of the rotor  102 . 
     In order to maximize the heat transfer rate between the rotor and the cooling surface, the surface conditions of the rotor and the cooling surface must be selected so that absorptivity and emissivity are high in their operational temperature ranges. Other regions of the transfer plate and the rotor not involved in heat transfer are typically designed to have poor radiation heat cooling surface properties to minimize the cooling of other components in the centrifuge chamber. The geometric view factor between the cooling surface  108  and the surface of the rotor  102  can be greater than 0.5, or greater than 0.6, or greater than or equal to 0.7. In some embodiments the view factor approaches 1.0, for example, 0.97 or greater. 
     The cooling surface  108  is designed to cool the rotor  102 . Heat from the rotor  102  is absorbed through the air (or vacuum) separating the rotor  102  and the cooling surface  108 . Heat is transferred in the opposite direction when the cooling surface  108  is used to heat the rotor  102 . The thermal element  107  controls the amount and rate of cooling (or heating) of the rotor  102  by controlling the temperature of the cooling surface  108 . 
     The thermal element  107  can cool or heat the rotor  102  by a number of mechanisms. For example, the thermal element  107  may comprise coils containing a circulating fluid for heating or cooling the thermal element  107  and thus the rotor  102 . In some embodiments the thermal element  107  is a thermoelectric device (also called a Peltier device). Such devices have two sides, a “hot” side and a “cool” side. When direct current flows through the device, heat from the “cool” side is brought to the “hot” side. The “hot” side is typically attached to a heat sink so that it remains at ambient temperature, while the “cool” side drops below ambient temperature. By reversing polarity, the temperature of the two sides can be reversed. A typical thermoelectric device used in the centrifuges of the invention operates at 60 W max at 0° C. delta T across it. The maximum delta T across the device used in this invention is usually 55° C. 
     The thermal element  107  may be thermally coupled to a heat sink  110  to dissipate the heat absorbed by the thermal element  107  and the heat generated by the operation of the thermal element  107  itself. The thermal coupling of the heat sink  110  can be through direct contact of through highly thermally conductive passive devices such as heat pipes. The heat sink  110  is often cooled with ambient air. A fan may blow air over the heat sink to help dissipate the heat from the heat sink to outside the centrifuge. Alternatively, a circulating fluid may be used to dissipate the heat from the heat sink. 
       FIG.  2    is a side view of another embodiment of a centrifuge chamber  201  of the invention comprising a floor  202  and a wall  203 . In this embodiment the thermal element  204  (e.g., a thermoelectric device) and transfer plate  206  comprising a cooling surface  205  are spaced apart from the wall  203  of the centrifuge chamber  201 . The thermal element  204  is attached to a mechanical interface  208 , which encloses a heat pipe  209  connected to a heat sink  210 . The mechanical interface,  208  is designed to effectively transfer thermal energy to the embedded heat pipes. Heat pipes are well known to those of skill in the art and are not described in detail here Briefly, a heat pipe comprises a fluid (e.g., ammonia, alcohol, or water) inside a thermally conductive solid surface (e.g., copper). The fluid turns into a vapor by absorbing heat from the thermally conductive solid surface at the hot interface and travels along the heat pipe to the cold interface and condenses back into a liquid. The liquid is then returned to the hot and the cycle repeats. One of skill will recognize that different heat pipe designs have different operational ranges. For example, the operational range of water filled heat pipes is typically 5 C to 120° C. The connection between the mechanical interface  208  and the floor  202  can include a seal  211  to maintain a vacuum in the chamber  201 . 
     In some embodiments, to provide maximum heating or cooling of the rotor  207  while minimizing heating or cooling of the chamber walls  203 , the cooling surface  205  is positioned proximate to the rotor  207  and apart from the walls  203  of the chamber, such that the minimum distance between the cooling surface  205  and the surface of the rotor  207  is less than the minimum distance between the cooling surface  205  and any wall  203  of the centrifuge chamber  201 . In some embodiments, the average distance between the cooling surface  205  and the surface of the rotor  207  is less than the average distance between the cooling surface  205  and the walls  203 . Other factors can also affect the heat transfer rate, such as, emissivity/adsorption, view factor and temperature of the surface. For example, adding a an actively cooled lid to the cooling system can affect cooling by improving the view factor. In some embodiments, the surface of the thermal element  205  may contact a wall  203 . In these embodiments, to maximize the exchange of heat between the cooling surface  205  and the rotor  207  while minimizing the exchange of heat between the cooling surface  205  and the wall  203 , the area of the thermal element  204  in contact with the wall  203  is less than the area of the cooling surface  205  proximate the rotor. Alternatively, the minimum distance between the center of the cooling surface  205  and the surface of the rotor  207  can be less than the minimum distance between the center of the cooling surface  205  and a surface of the wall  203 . Minimizing the heating or cooling of the chamber walls minimizes the energy wasted in heating or cooling the rotor  207 . Alternatively, to minimize the heat transfer to other components in the vacuum chamber a thermally insulating layer can be added to the portions of cooling surface  205  facing the chamber walls. This would typically be comprised of one or a plurality of highly reflective surfaces which have a minimized conduction path between the reflective surfaces. 
       FIG.  3 A  is a side view and  FIG.  3 B  is top view of another embodiment of the invention. In this embodiment, a plurality of cooling assemblies  301 , are positioned on the chamber floor  302  of the centrifuge chamber  303  surrounding the rotor  304 . Each cooling assembly  301  comprises a thermal element  305  (which can be a thermoelectric device) connected to a heat transfer plate  308  and a heat sink  307  through heat pipes  309  and heat spreaders  306 . Heat is absorbed from the rotor  304  by the surface of transfer plate  308  and transferred to heat pipes  309  and ultimately to the heat sink  307 . 
       FIG.  4    is a side view and  FIG.  4 B  is a top view of an embodiment of the invention similar to that shown in  FIGS.  3 A and  3 B . In this embodiment, a plurality of cooling assemblies  401 , are positioned on the floor  402  of the centrifuge chamber  403  surrounding the rotor  404 . Each cooling assembly  401  comprises a thermal element  405  (which can be a thermoelectric device), which is positioned between a transfer plate  408  and a heat spreader  406 . Heat is absorbed from the rotor  404  by the surface of transfer plate  408  and transferred through heat pipes  409  and ultimately to the heat sink  407 . 
       FIG.  5    is a side view of another embodiment in which cooling surface  508  is spaced apart from the wall  502  of the chamber  503  and is proximate to the rotor  509 . In this embodiment, the cooling assembly  501  is attached to the wall  502  of the chamber  503 , instead of the floor  510 . As in other embodiments, a plurality of cooling assemblies  501  may be positioned in the chamber  503 . Each module comprises thermal element  504  connected to a heat sink  505 . Heat pipes  506  connect the thermal element  504  to the transfer plate  507  so that the cooling surface  508  is proximate to the rotor  509 . 
       FIGS.  6 A and  6 B  depict a cooling assembly  601  comprising transfer plates  602 , thermal elements  603  and heat pipes  604 , which thermally couple the thermal elements  603  to the heat sink  605 . The cooling assembly  601  is attached to the floor  606  by a base plate  607 , which includes a vacuum seal  608 .  
       FIGS.  7 A,  7 B and  7 C  depict cooling assemblies  701  comprising transfer plates  703  and  702 , which conduct heat to and from a thermoelectric device (not shown) inside the cooling assembly  701  and a rotor. In this embodiment, a TE block  704  is included to provide a mechanical interface to the thermoelectric device and to provide a thermal path from the thermoelectric device to heat pipes  710 . The heat pipes  710  provide a thermal connection to the heat sink assembly  706 , which includes a fan  707  to cool the heat sink. The cooling assembly  701  is held in place on the floor of the centrifuge chamber by vacuum clamps  708 , which pull the vacuum sealing surface  705  and  0  ring  709  against the floor to provide a vacuum seal.  FIG.  7 B  shows the position of  6  heat pipes  710  inside the cooling assembly  701 .  FIG.  7 C  shows the positioning of the cooling assemblies  701  around a rotor  711  thereby creating thermal compartment  712  around the rotor  711 . An optical element  713  is outside the thermal compartment  713 . The optical element  713  receives a beam of light from a light source  716 , and delivers the beam of light onto a window  714  in the rotor  711  to illuminate a sample in the rotor  711 . The optical element  713  can be any suitable combination of mirrors, lenses, optical fibers, or the like to define a light path. In the embodiment shown in  FIG.  7 C , the optical element  713  is rotatable along a vertical axis to allow access to the rotor  711 . The rotor  711  includes a window  714  to view the sample. The centrifuge includes an optical element  713  disposed outside the centrifuge chamber to deliver a beam of light to the window  714 . The light source  717  and a detector  716  disposed outside the centrifuge chamber, wherein the light source  717  is arranged to deliver a beam of light to the optical element  713 , wherein the rotor includes a second window  715  (bottom side of rotor  711 ), wherein the detector  716  is arranged to receive a beam of light emitted through the second window  715 .  
     The cooling surface defined by transfer plates  703  on the thermal elements  701  can be in a variety of dimensions and shapes. For example, the cooling surface can be in the shape of a one-piece ring that entirely encircles the rotor  711  when looking down from above the rotor  711 . In this embodiment, the ring has a bottom with openings needed for the analytical module, surrounding the rotor from three sides and forming a thermal can. This embodiment may also comprise a thermally coupled top attached to the walls of the can. This would completely enclose the rotor. The top has corresponding openings to allow the operation of the analytical modules. 
     In another embodiment, each thermal element  701  includes two cooling surfaces. The first is disposed inside the centrifuge chamber  712  proximate the rotor  711  to control the temperature of the rotor  711 , usually the side of the rotor  711 . The second is disposed proximate to the drive to cool the drive as it spins the rotor  711 . The second surface can be attached to the floor of the centrifuge. The first and second surfaces can be continuous. In other embodiments, the cooling surface is formed by two or more curved or arc segments positioned around the rotor. 
     In other embodiments, the cooling surface is formed by two or more straight segments positioned outside the periphery of the rotor. In some embodiments, the radial position of the cooling surface is adjustable to accommodate different-sized rotors in the centrifuge chamber. In such embodiments, the thermal element is reversibly coupled to the cooling surface to allow removal and/or prepositioning of the cooling surface from the centrifuge chamber. In one embodiment, the centrifuge is an analytical ultracentrifuge and the cooling surface comprises three arc segments centered 120° apart. Spacing between the arc segments provides space for up to three optical modules to be positioned inside the centrifuge chamber between the arc segments. The optical modules can include, for example, an absorbance-scanning module, a fluorescence scanning module, and an interference imaging module. The optical module can be positioned below the floor of the chamber and include a light pipe to deliver illuminating light onto the top of the rotor to irradiate a sample in the rotor. 
       FIG.  8    (including  FIGS.  8 A- 8 K ) shows different embodiments of the invention showing different arrangements of rotors  801  and cooling surfaces  802  of the invention. As shown there, the shape of the cooling surface opposed to the rotor can be flat or curved. The surface may be curved to match a curve of the outer surface of the rotor. The thermal control surface may extend above or below the opposing surface of the rotor. The cooling surface may extend even with the opposing surface of the rotor. The rotor  801  may have a non-circular cross-section, with an effective diameter defined as twice the distance from the axis of rotation to the farthest point on the surface of the rotor  801  from the axis. In some embodiments of the invention, the cooling surface(s)  802  forms a ring around the rotor  801 , where the ratio of the effective diameter of the rotor  801  to the diameter of the ring formed by the cooling surfaces  802  is greater than 0.5, or greater than 0.6, or greater than 0.7.   
     A temperature gradient and consequently convective mixing can occur in the sample cell due to differences in radiative heat transfer from the top/bottom of the sample cell and sample fluid. This convective differential can be caused by a temperature gradient throughout the rotor or by a difference in direct radiative heat transfer into the sample fluid from above and below the sample. 
     To decrease the radiative heat transfer imbalance into the top and bottom of the sample, cooling surfaces are maintained above and below the rotor which are as close to the same temperature as possible and as close to the rotor temperature as possible. This minimizes the convective mixing which occurs in the sample. 
     Decreasing radiative heat transfer imbalance can also be accomplished by increasing the wall height of the cooling surfaces, adding a cover to the cooling surfaces, adding heat shields to the bottoms of the optical element and/or adding a partially insulating material between the cooling surface walls and bottom. Through these means, the system can be tuned to minimize the convective mixing in the sample. 
     The outside of the cooling surfaces can be shiny to reduce the absorption and emissivity and therefore heat transfer between the chamber and the cooling surfaces. The cover can include a double layer of insulating material to minimize the thermal transfer between the cover and the chamber. 
     It is understood that the embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims.