Patent Publication Number: US-2022226829-A1

Title: Systems for performing cellular analysis and related devices for conditioning environments adjacent chips in such systems

Description:
FIELD OF THE DISCLOSURE 
     The present disclosure relates generally to systems for performing cellular analysis and, in particular, to systems for performing cellular analysis and related devices for conditioning environments adjacent chips in such systems. 
     BACKGROUND 
     Systems for performing cellular analysis such as the Berkley Lights® Beacon® platform may be used to perform a variety of cellular analyses. These systems may include microfluidic devices that are used to process micro-objects such as biological cells. To select and move the biological cells, the systems sometimes include one or more optoelectric positioners. 
     The systems can maintain the temperature within the systems between about 2° C. and 60° C. Temperature is known to affect metabolic functioning of living cells. Maintaining the cells between 2° C. and 8° C. may reduce and/or halt certain functions such as protein secretion and receptor internalization. 
     SUMMARY 
     In accordance with a first example, a device for conditioning an environment adjacent a chip in a system for performing cellular analysis includes a cover for being disposed adjacent the chip and including a planar body having a top surface, a bottom surface, and an outer edge surface. The cover includes a central opening extending between the top surface and the bottom surface and bounded by an inner edge surface of the cover. The cover also includes a fluid inlet extending into the body from the outer edge surface between the top surface and the bottom surface. The fluid inlet is arranged to accept a gas to be delivered to the central opening. The cover also includes a plurality of fluid outlets defined in the inner edge surface and in fluid communication with the fluid inlet. The plurality of fluid outlets are arranged to receive the gas from the fluid inlet and exhaust the gas into the central opening. 
     In accordance with a second example, a system for performing cellular analysis includes an enclosure. The system also includes an imaging system disposed within the enclosure. The system also includes a chip to carry cells for analysis within the enclosure and a chip clamp to clamp the chip in place. The system also includes a local air conditioner arranged to reduce humidity immediately adjacent the chip. The system also includes a controller to cause the imaging system to obtain imaging data of the cells on the chip. 
     In further accordance with the foregoing first and/or second examples, an apparatus and/or method may further include any one or more of the following: 
     In accordance with one example, the cover includes a first layer including the top surface and a second layer including the bottom surface. 
     In accordance with another example, the first layer defines the central opening and includes the inner edge. 
     In accordance with another example, the second layer includes inner walls that surround the central opening. 
     In accordance with another example, the fluid outlets are defined by the inner walls. 
     In accordance with another example, the fluid outlets are outwardly spaced relative to the inner edge of the central opening. 
     In accordance with another example, a mask portion of the first layer extends between the inner walls and the central opening. The mask portion and the inner walls defines a chamber that covers the chip. 
     In accordance with another example, a plurality of fluid channels are arranged between the first layer and the second layer. Respective ones of the fluid outlets are associated with the fluid channels. 
     In accordance with another example, the first layer and the second layer are positioned adjacent one another to form the fluid channels therebetween. 
     In accordance with another example, the cover includes a plurality of locating pins extending from the bottom surface. The locating pins are arranged to be received adjacent the chip. 
     In accordance with another example, further including a plurality of cover clips having slots that receive portions of the outer edge surface of the cover. The cover clips are to be arranged to secure the cover relative to the chip. 
     In accordance with another example, the cover includes a plurality of fasteners. The cover clips include slots. The fasteners are received within the slots. 
     In accordance with another example, the local air conditioner includes a cover. The cover is to be disposed adjacent the chip and defines a central opening. The imaging data of the cells to be obtained through the central opening. 
     In accordance with another example, the cover includes a planar body having a top surface, a bottom surface, and an outer edge. The central opening extends between the top surface and the bottom surface and defines an inner edge. 
     In accordance with another example, the cover further includes a fluid inlet extending into the body from the outer edge between the top surface and the bottom surface. The cover also includes a plurality of fluid outlets in communication with the fluid inlet and arranged to exhaust a gas out of the central opening. 
     In accordance with another example, the cover includes a first layer including the top surface and a second layer including the bottom surface. A plurality of fluid channels are arranged between the first layer and the second layer. Respective ones of the fluid outlets are associated with the fluid channels. 
     In accordance with another example, the first layer defines the central opening and includes the inner edge and the second layer includes inner walls that surround the central opening and define the fluid outlets. A mask portion of the first layer extends between the inner walls and the central opening and the inner walls defines a chamber that covers the chip. 
     In accordance with another example, further including a second chip to carry cells for analysis within the enclosure and a second chip clamp to clamp the second chip in place. The local air conditioner is arranged to reduce humidity immediately adjacent the second chip. 
     In accordance with another example, the local air conditioner includes a manifold arranged to direct a gas toward the chip and the second chip. The gas reduces the humidity immediately adjacent the chip and the second chip. 
     In accordance with another example, the present invention is directed to a method for improving the viability of cell which is to be subjected to optoelectronic positioning (OEP) comprising performing the OEP at a temperature below dew point such that the cell can be visualized while the cell is being loaded, wherein the device of the presently claimed invention is utilized in order to decrease condensation on a chip in a system for performing cellular analysis. 
     In accordance with another example, the OEP is performed at a temperature selected from the group consisting of about 3° C., about 4° C., about 5° C., about 6° C., about 7° C., about 8° C., about 9° C., about 10° C., about 10.5° C., about 11° C., about 12° C., about 13° C., about 14° C., about 15° C., about 16° C., about 17° C., about 18° C., about 19° C., about 20° C., about 21° C., and about 22° C. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic illustration of a system for performing cellular analysis in accordance with a first disclosed example. 
         FIG. 2  is an illustration of a system for performing cellular analysis in accordance with a second disclosed example. 
         FIG. 3  illustrates an isometric bottom-view of a cover of a local air conditioner of the system of  FIG. 2 . 
         FIG. 4  illustrates a plan-bottom view of a first layer of the cover of  FIG. 3 . 
         FIG. 5  illustrates a plan-top view of the cover of  FIG. 3 . 
         FIG. 6A  illustrates an isometric bottom-up view of the cover and a plurality of cover clips. The cover clips are in a first position receiving an outer edge surface of the cover. 
         FIG. 6B  illustrates an isometric bottom-up view of the cover and the cover clips in a second position receiving the outer edge surface of the cover. 
         FIG. 7A  illustrates a chip having a plurality of wells that is covered by condensation and/or frost. 
         FIG. 7B  illustrates the chip of  FIG. 7A  with the condensation and/or frost removed (or reduced) after using the example covers disclosed herein. 
         FIG. 8A  shows that cold optoelectronic positioning (OEP) with claimed device enhances on-chip TCR T cell viability 18 hours after OEP. 
         FIG. 8B  shows that cold OEP with claimed device enhances on-chip TCR T cell proliferation 96 hours after OEP. 
     
    
    
     DETAILED DESCRIPTION 
     Although the following text discloses a detailed description of example methods, apparatus and/or articles of manufacture, it should be understood that the legal scope of the property right is defined by the words of the claims set forth at the end of this patent. Accordingly, the following detailed description is to be construed as examples only and does not describe every possible example, as describing every possible example would be impractical, if not impossible. Numerous alternative examples could be implemented, using either current technology or technology developed after the filing date of this patent. It is envisioned that such alternative examples would still fall within the scope of the claims. 
     The examples disclosed herein relate to systems and related devices for performing cellular analysis that reduce the likelihood of condensation forming when a temperature within the system is reduced below a dew point of the ambient air. If condensation forms within such systems, the quality of the imaging data may be reduced and may not be usable. Moreover, using the disclosed examples while operating the associated systems at lower temperatures allows for enhanced cell viability during manipulation workflows such as, for example, T cell work flows. 
       FIG. 1  is a schematic illustration of an example system  100  for performing cellular analysis in accordance with a first disclosed example. The system  100  includes an enclosure  102  that may be accessed and sealed via a door  106 . 
     An imaging system  112 , an actuator  114 , and a plurality of chips  116 ,  118  are disposed in the enclosure  102 . The imaging system  112  may include, for example, an optical train system, a LED light projector, etc. The imaging system  112  is configured to obtain imaging data and to perform fluorescence detection (e.g., cell counting) of cells carried by the chips  116 ,  118 . The actuator  114  is configured to move the imaging system  112  from a position associated with obtaining imaging data from one of the chips  116  or  118  to a position associated with obtaining imaging data from another one of the chips  116  or  118 . In the example shown, the imaging system  112  is positioned above the second chip  118  and, thus, is positioned to obtain imaging data associated with the second chip  118 . Alternatively, the actuator  114  may be configured to move a platform (not shown) carrying the chips  116 ,  118  relative to the imaging system  112  that is stationary. 
     The chips  116 ,  118  are shown including a plurality of wells  120 . The wells  120  may be used to isolate one or more cells for analysis and/or culturing. The wells  120  may be nanowells or microwells. 
     The system  100  also includes a plurality of chip clamps  122  and a plurality of positioners  124 . The chip clamps  122  may be used to clamp the chips  116 ,  118  in place and the positioners  124  may be used to move one or more cells on the chips  116 ,  118  into and/or out of the wells  120 . In the example shown, the chips  116 ,  118  are positioned on corresponding heater/chiller manifolds  125  that are coupled to a heater  126  and a chiller  127  of the system  100 . The temperature of the chips  116 ,  118  may be controlled via the heater/chiller manifolds  125  by the heater  126  and the chiller  110 . While the heater  108  and the chiller  110  are shown disposed within the space  104 , the heater  126  and/or the chiller  127  may disposed outside of the space  104  but in communication with the space  104 . 
     The system  100  also includes a local air conditioner  130 . In the example shown, the local air conditioner  130  is configured to condition a plurality of environments  132 ,  134  (e.g., local environments) adjacent the chips  116 ,  118 . Conditioning the environments  132 ,  134  may include reducing humidity adjacent the chips  116 ,  118  by providing dry air at a positive pressure. The dry air provided may decrease the humidity within the environments  132 ,  134  and reduce the likelihood of condensation forming on or around the chips  116 ,  118 . As a result, even if the temperature within the enclosure  102  and/or the chips  116 ,  118  reaches the dew point of the ambient air, the local air conditioner  130  is configured to reduce the likelihood that condensation forms on the chips  116 ,  118 , allowing for the acquisition of quality imaging data. Put another way, the local air conditioner  130  reduces the likelihood that a field of view (FOV) of the imaging system  112  is obscured via condensation and/or ice, allowing for the imaging system  112  to capture imaging data of a threshold amount of the wells  120  of the chip  116 ,  118 . While dry air is mentioned, other gases may be used. Some of these gases have a lower boiling point such as, for example, Nitrogen (N) and Carbon Dioxide. 
     In the example shown, the local air conditioner  130  includes a plurality of covers  136 ,  138  (e.g., masks), a plurality of valves  140 ,  142 , a manifold  144 , and a source  146  of gas (e.g., dry compressed air). Flow lines  147  fluidly couple the covers  136 ,  138  and the valves  140 ,  142 , the valves  140 ,  142  and the manifold  144 , and the manifold  144  and the source  146 . In practice, the source  146  flows the gas to the manifold  144  and the manifold  144  directs and distributes the gas through associated ports  148  of the manifold  144  and through the flow lines  147  toward the valves  140 ,  142  and to the covers  136 ,  138 . 
     The covers  136 ,  138  may be integral to the respective chip clamps  122  or may be removably coupled to or adjacent to the chip clamps  122 . Alternatively, the covers  136 ,  138  may be integrated into the system  100  in other ways that allow for the covers  136 ,  138  to condition the environments  132 ,  134 . 
     As shown in  FIG. 1 , the covers  136 ,  138  define central openings  149  that allow the imaging system  112  to obtain imaging data of the chips  116 ,  118  and allow the gas provided by the source  146  to exhaust from the covers  136 ,  138 . The valves  140 ,  142  are actuatable to selectively flow gas into the respective environments  132 ,  134 . For example, when the imaging system  112  obtains imaging data of the second chip  118 , the first valve  140  is closed and the second valve  142  is open. And, when the imaging system  112  obtains imaging data of the first chip  116 , the second valve  142  is closed and the first valve  140  is open. In other versions, all valves  140 ,  142  remain open during imaging of all chips  116 ,  118  to ensure no condensation forms. The valves  140 ,  142  may be manually actuated by an operator or automatically actuated using, for example, a pneumatic or electric actuator controlled by a controller  152 . 
     As seen in  FIG. 1 , the controller  152  includes an interface  154 . The interface  154  is positioned outside of the enclosure  102  to allow for operator accessibility. In the example shown, the interface  154  is operatively coupled to the controller  152  and to the local air conditioner  130  and may be used to control the imaging system  112 , the actuator  114 , and the local air conditioner  130 . Controlling the imaging system  112  includes causing the imaging system  112  to obtain imaging data of cells carried by one of the chips  116 ,  118 . Controlling the actuator  114  includes causing the actuator  114  to move the imaging system  112  between a position associated with obtaining imaging data of the first chip  116  and a position associated with obtaining imaging data of the second chip  118 . Controlling the local air conditioner  130  includes controlling the conditioning of the environments  132 ,  134 . For example, the local air conditioner  130  may selectively reduce the humidity or otherwise condition the environments  132 ,  134  depending on a temperature within the enclosure  102  and/or a likelihood that condensation will form on or around the chips  116 ,  118 . 
       FIG. 2  is an illustration of an example system  200  for performing cellular analysis in accordance with a second disclosed example. The system  200  may be partially implemented by the Beacon® platform by Berkley Lights® and is similar to the system  100  of  FIG. 1 . Elements of the system  200  which are the same or similar to the system  100  are designated by the same reference numeral, incremented by 100 (e.g., the imaging system  112  and an imaging system  212 ). However, the system  200  is different from the system  100  of  FIG. 1  in that four chips  216  are shown instead of two chips  116 ,  118  and four chip clamps  222  are shown instead of two. Also, a local air conditioner  230  of  FIG. 2  includes a manifold  244  having four ports  248 . The manifold  144  receives gas through a single inlet  249  and distributes the gas to the plurality of ports  248 . 
     Four valves  240  are coupled to the ports  248  of the manifold  344  to selectively control gas flow out of the port  248 , through flowlines  247 , and to a cover  236 . The valves  240  have manual actuators  250  formed by knobs that are rotatable to open and close (actuate) the valves  240 . In other embodiments, the valves  240  may be actuated automatically by a system controller including memory and a processor executing logic programmed to open and close the valves  240  in accordance with a desired process routine. While  FIG. 2  only shows one cover  236 , alternative versions would have four covers  236 , one per chip  216 . Those covers may be formed of a single unit that cover all four of the chips  216  or may be formed on any number of units (e.g., 2, 3, 4) that cover the chips  216 . 
     The manifold  244  is a cuboid (a rectangular prism) having the ports  248  disposed along one of the longer sides  251  and having an opposing one of the longer sides  252  positioned immediately adjacent and attached to a surface  253  of the system  200 . The manifold  244  can be removably attached to the surface  253  of the system  200  using magnets, for example. The magnets may be received within one or more recesses of the manifold  244  and may be secured within the recesses using, for example, adhesive or the magnets themselves.  FIG. 2  shows the cover  236  of the local air conditioner  230  positioned adjacent an associated one of the chips  216 . However, alternatively, between one and four covers  236  (one per chip  216 ) may be included and the manifold  244  and the associated valves  240  may be used to selectively flow gas to those covers  236 . 
     In the example shown, a de-humidified environment can be created directly above the surface of the chip  222  by inserting locating pins  298 ,  300  (the locating pins are more clearly shown in  FIG. 3 ) of the cover  236  into holes defined by the chip clamp  222  or the system  200 , thereby securing the cover  236  to the chip clamp  222 . The manifold  244  may be attachable to the surface  253  of the system  200  via magnets. One of the flowlines  247  may be coupled to an air input within the system  200  via a quick connect coupler. The flowline  247  also couples the manifold  244  and the cover  236 . The compressed air can flow to the cover  236  via the flowline  247  and the manifold  244 . In the example shown, the pressure of the compressed air flowing to the cover  236  is adjustable by rotating the actuator  250 . In some examples, the actuator  250  is positioned to a flow rate that allows dehumidification of the chip  22  at a threshold temperature. The temperature of the system  200  and/or the temperature immediately adjacent the chip  216  may be adjusted using, for example, the interface  154  of the system  200 . In an example, after the threshold temperature within the system  200  is satisfied, a steady flow of air is continuously directed across a surface of the chip  222  throughout imaging and/or OptoElectroPositioning (OEP) cell manipulation experiments. 
       FIG. 3  illustrates an isometric bottom-view of the cover  236 . In the example shown, the cover  236  is rectangular and includes a planar body  254  having a top surface  256  (hidden in  FIG. 3 ), a bottom surface  258 , and an outer edge surface  260 . A central opening  213  defines an inner edge surface  262 . The central opening  213  is rectangular, which conforms to a desired field of view of the imaging system  112  to capture the desired target area of the chip  216 . However, the central opening  213  may be a different shape such as, for example, oval, triangular or any other shape that allows the imaging data of the associated chip  216  to be obtained. The shape of the central opening  213  can correspond to the shape formed by the outer edge surface  260 , as shown. Alternatively, the shape of the central opening  213  may be different than the shape formed by the outer edge surface  260 . For example, the central opening  213  may be circular and the outer edge surface  260  may form a square. 
     The cover  236  also includes a fluid inlet  264  and a plurality of fluid outlets  266 . The fluid inlet  264  extends into the body  254  from the outer edge surface  260  between the top surface  256  and the bottom surface  258  and is formed by a male interface  267 . The male interface  267  extends substantially perpendicularly from the outer edge surface  260  and has a circular cross-section. However, the inlet  264  may be differently formed. As an example, the inlet  264  can be formed as a port that receives a male adapter of the flowline  247 . 
     The fluid outlets  266  are in fluid communication with the fluid inlet  264  via flow paths within the cover  236  and are arranged to exhaust gas out of the central opening  213 . Specifically, the fluid outlets  266  are to flow the gas over a top surface of an associated chip  216  to reduce the likelihood of condensation and/or ice forming and interfering with the imaging procedure. 
     In the illustrated example, the cover  236  includes a first layer  268  and a second layer  270 . To secure the first and second layers  268 ,  270  together, the layers  268 ,  270  may include mating structures. As an example, the first layer  268  can include protrusions (male structures) that extend from a mating surface  271  of the first layer  270  and an adjacent mating surface  272  of the second layer  270  can define apertures (female structures). When the first and second layers  268 ,  270  are stacked, the protrusions and the apertures align to allow the protrusions to be received within the apertures and for the layers  268 ,  270  to be coupled together. The interaction between the protrusions and the apertures may form a snap-fit, friction fit, press fit, or other connection. While the first layer  268  is mentioned potentially including protrusions and the second layer  270  is mentioned potentially including apertures, alternatively, the first layer  268  and/or the second layer  270  may include either of the protrusions or the apertures or may be held together in other ways (e.g., adhesive). Furthermore, in other examples such as the one shown in  FIGS. 3-5 , the layers  268 ,  270  can be held together via fasteners  204  (the fasteners  304  are best shown in  FIG. 5 ). While the cover  236  is illustrated including the first and second layers  268 ,  270 , the cover  236  may alternatively include a single layer and may be formed using, for example, additive manufacturing techniques or traditional machining techniques. Some traditional machining techniques include, for example, drilling, or milling a solid piece of material. 
     The second layer  270  and a portion  273  of the first layer  268  include inner walls  274   a ,  274   b . The inner walls  274   a ,  274   b  define a central recess  226  in the bottom of the cover  236 . The central recess  226  is shaped similar to but larger in dimension than the central opening  213 . The central recess  226  may be sized such that when the cover  236  is positioned adjacent the chip  216 , the chip  216  is positioned (or at least substantially positioned) within a dimensional envelope of the central recess  226 . Alternatively, only a portion of the chip  216  is positioned within the dimensional envelope of the central recess  226  when the cover  236  is positioned adjacent thereto or the chip  216  is entirely outside of the dimensional envelope of the central recess  226 . 
     In the example shown, the cover  236 , the central opening  213 , and the central recess  226  are rectangular (e.g., square) and may be sized to be positioned about a correspondingly sized/rectangular one of the chips  216 . Additionally, to define the central recess  226 , the first layer  268  defines a mask portion  276  that cantilevers inward toward the center of the cover  236  over the central recess  226  and terminates at the inner edge surface  262  of the central opening  213 . So configured when the cover  236  is disposed on the chip  216  as shown in  FIG. 2 , the inner walls  274   a ,  274   b  may be positioned along the edges (e.g., outer edges) of the chip  216 , thereby aligning the cover  236  in position, while the mask portion  276  extends at least partly over the chip  216  without obstructing the target area of the chip  216  to be captured by the imaging system  212 . 
     The fluid outlets  266  are defined by the inner walls  274   a ,  274   b  and are outwardly spaced relative to the inner edge surface  262  of the central opening  213 . Thus, the fluid outlets  266  are arranged to flow gas from the edges of the chip  216 , beneath the mask portion  276  of the first layer  168 , and toward a center of the chips  216 , out through the central opening  213 , so it can be understood that the mask portion  276  and the inner walls  274   a ,  274   b  define a chamber  278  (e.g., a micro-chamber) above the chip  216 . The chamber  278  contributes to a local environment (e.g., the environment  132 ) about the chip  216  that may be controlled using the local air conditioner  206 . Meaning, at least the mask portion  276  serves to restrict the flow of gas to the intended local environment immediately above and adjacent the chip  216 , while simultaneously allowing the imaging system  112  to capture unobstructed images through the central opening  213 , 
     To illustrate further,  FIG. 4  shows a plan-bottom view of the first layer  268 . A plurality of fluid channels  280  are defined by the first layer  268 . In the example shown, the fluid channels  280  include a perimeter fluid channel  282  and a plurality of transverse fluid channels  284 . The perimeter fluid channel  282  is fluidly coupled to the fluid inlet  264  and follows in a square (or rectangular) pattern along sides  286 ,  288 ,  290 ,  292  of the first layer  268 . In the example shown, the transverse fluid channels  284  are fluidly coupled to extend radially inward from the perimeter fluid channel  282  to the fluid outlets  266 . Thus, the transverse fluid channels  284  flow gas from the perimeter fluid channel  282  to an associated respective one of the fluid outlets  266 . The transverse fluid channels  284  are substantially equally spaced from one another such that the transverse fluid channels  284  on the first and third sides  289 ,  290  of the first layer  268  are mirror images of one another and the transverse fluid channels  284  on the second and fourth sides  288 ,  292  of the first layer  268  are mirror images of one another. However, the transverse fluid channels  284  may be positioned in other ways. 
     Similarly, while not shown, the second layer  270  includes a plurality of fluid channels having a perimeter fluid channel and a plurality of transverse fluid channels. The fluid channels  280  of the first layer  268  are mirror images of the fluid channels of the second layer  270  such that when the first and second layers  268 ,  270  are stacked, fluid channels are defined that form the fluid outlets  266 . Alternatively, one of the layers  268 ,  270  may include grooves forming the fluid channels and the other of the layers  268 ,  270  may have a flat or non-grooved surface that forms a side of the fluid channels. The fluid channels and the fluid outlets  266  have a circular cross-section. However, the fluid channels and/or the fluid outlets  266  may have another cross-section. For example, the cross-section may be oblong, square, rectangular, etc. 
     Referring back to  FIG. 3 , when the first layer  268  and the second layer  270  are positioned immediately adjacent one another (i.e., stacked), the fluid channels  280  including the perimeter fluid channel  282  and the transverse fluid channels  284  of the first and second layers  268 ,  270  are positioned between the layers  268 ,  270 . The cover  236  of  FIG. 3  also includes a plurality of flanges  294 ,  296  and a plurality of locating pins  298 ,  300 . The flanges  294 ,  296  may be used to secure the cover  236  adjacent one of the chips  216  and the locating pins  298 ,  300  may be used to position and/or secure the cover  236  relative to one of the chips  216 . The locating pins  298 ,  300  may be received within apertures defined by the system  200  and/or the chip clamp  222 . In the example shown, the flanges  294 ,  296  define apertures  302  that receive the fasteners  304  (the fasteners are best shown in  FIG. 5 ) that are described in more detail in connection with  FIG. 5 . 
       FIG. 5  illustrates a plan-top view of the cover  236 . A plurality of cover clips  306 ,  308  (e.g., sliding clamps) are included. The cover clips  306 ,  308  each include a slot  320 . Fasteners  304  are received through the apertures  302  in the flanges  294 ,  296  and within a respective one of the slots  320 . An interaction between each fastener  304  and each slot  320  guides the relative movement between the cover clips  306 ,  308  and the fasteners  304 , as shown in  FIGS. 6A and 6B . Additionally or alternatively, the fasteners  204  may secure the layers  268 ,  270  together. 
       FIGS. 6A and 6B  are isometric bottom-up views of the cover  236  and the cover clips  306 ,  308 . The cover clips  306 ,  308  include first, second, third, fourth, and fifth legs  310 ,  312 ,  314 ,  316 ,  318 . The first, second and third legs  310 ,  312 ,  314  are arranged in a C-shape and define a first groove  322 . In the example shown, the first grooves  322  receive the flanges  294 ,  296  and, thus, the outer edge surface  260  of the cover  236  to assist in maintaining the cover  236  in its assembled or stacked state or, more generally, to assist in maintaining the position of the cover  236  to allow the cover  236  to form a border (or frame) about the chip  216 . In this configuration of the cover clips  306 ,  308 , the fourth and fifth legs  316 ,  318  of the chip clips  306 ,  308  are arranged in an L-shape extending downward from the third leg  314  and form second grooves  324  with the bottom surface  258  of the cover  236 . The second grooves  324  are adapted to receive a portion of the chip clamp  202  and/or an adjacent structure to secure the cover  236  adjacent the associated chip  204 . 
       FIG. 6B  illustrates the flanges  294 ,  296  fully positioned within the first groove  322  of the cover clips  306 ,  308 . In the position shown in  FIG. 6B , the cover clips  306 ,  308  are capable of receiving a portion of the chip clamp  202  and/or an adjacent structure to secure the cover  236  adjacent the associated chip  204 . To remove the cover  236  from being secured adjacent the chip clamp  202 , the cover clips  306 ,  308  are moved outwardly to the position shown in  FIG. 6A . Thus, using the disclosed examples, the covers  236  may be easily installed and uninstalled and may not require the existing cellular analysis system to be modified. 
       FIG. 7A  illustrates a chip  700  having a plurality of wells  702  that is covered by condensation and/or frost. The condensation and/or the frost makes identifying the cells  704  within the wells  702  more difficult. 
       FIG. 7B  illustrates the chip  700  with the condensation and/or frost removed (or reduced) after using the example covers disclosed herein. Without the condensation and/or the frost covering the wells  702 , the cells  704  may be more easily identifiable. 
     In other embodiments, the present invention is directed to a method for improving the viability of cell which is to be subjected to optoelectronic positioning (OEP) comprising performing the OEP at a temperature below dew point such that the cell can be visualized while the cell is being loaded, wherein the device of the presently claimed invention is utilized in order to decrease condensation on a chip in a system for performing cellular analysis. In certain embodiments, the OEP is performed at a temperature selected from the group consisting of about 3° C., about 4° C., about 5° C., about 6° C., about 7° C., about 8° C., about 9° C., about 10° C., about 10.5° C., about 11° C., about 12° C., about 13° C., about 14° C., about 15° C., about 16° C., about 17° C., about 18° C., about 19° C., about 20° C., about 21° C., and about 22° C. 
     From the foregoing, it will be appreciated that the above disclosed apparatus, methods and articles of manufacture enable cellular analysis to be conducted below the dew point of ambient air without or with a reduced amount of condensation forming adjacent the chips on which the analysis is being conducted, by providing for movement of air (either sporadically or continuously) in the local environment adjacent to the chips by the unique covers. Thus, the disclosed examples enable lower temperatures such as, for example, between about 2° C. and 8° C. to be maintained for extended periods while obtaining unobstructed cellular imaging data. As a result, cellular analysis and/or receptor/ligand assay may be executed at lower temperatures allowing for novel antibodies to be potentially discovered. Additionally, when the local air conditioners are not integral to the cellular analysis systems and, thus, are removable, the covers disclosed may be installed and/or removed relatively easily and, in some examples, without modifying the existing system. 
     Optoelectronic Positioning (OEP) and fluorescent imaging on the Berkeley Lights Beacon requires optical clarity through the glass surface of the nanofluidic chip. The presently claimed device enables OEP manipulation of objects and fluorescent data generation on the Berkeley Lights Beacon platform at temperatures below the specific dew point of water in the room by providing a steady evenly-dispersed flow of air across the surface of the chip while mounted on the nest. OEP induces a transient voltage gradient on the cells during the positioning process and this electrical current can have deleterious effects on mammalian cells in-vitro. In this set of experiments we have validated the hypothesis that reducing the temperature of the cells from 36° C. to 10.5° C. (enabled by the claimed device) during OEP loading of transduced human T cells leads to better cell survival and more effective antigen specific proliferation. 
     Normal donor human T cells were transduced with a GFP lentiviral construct encoding a TCR specific for an investigational cancer antigen. T cell cultures were expanded in Xuri bioreactors (GE) for 10 days, analyzed via FACS to confirm expression of the transduced TCR, and frozen down for long term storage in LN2. Vials containing transduced T cells (TCR T) were thawed, cultured in G-Rex plates (Wilson Wolf) at 36° C., 5% CO2 for greater than 3 days prior to being loaded onto the Berkeley Lights Beacon. The Beacon was initialized by loading 2 OS3500 nanofluidic chips (Berkeley Lights) into the nest hardware, wetting the chip per manufacturer&#39;s protocols, and flushing with growth media containing human AB serum. Gibco Dynabeads Human T-Activator CD3/CD28 (Thermofisher) were loaded into the pens using a combination of OEP and gravity. Excess unpenned beads were flushed out of the system to waste. Next, TCR T cells were stained with DAPI viability dye (Thermofisher) and manually loaded onto the 2 chips. The claimed device was installed over one of the Beacon nests containing a OS3500 and air supply was initiated allowing air to flow to the claimed device. Temperature of the claimed device nest was reduced to 10.5° C. while the nest without the claimed device was temperature controlled to 36° C. OEP pen loading of single viable TCR T expressing cells (DAPI−/GFP+) was then performed at both 10.5° C. and 36° C. temperature conditions using the Target Penning Selection (TPS) application of the Berkeley Lights Cell Analysis Suite (CAS) software. Unpenned TCR T were flushed out of the OS3500 chips to waste and images of each Field of View (FOV) of the chip containing cells and beads were captured using the Brightfield (BF), DAPI, and the FITC color cubes. Both chips were then removed from the Beacon and cultured on the Berkeley Lights Culture Station at a vertical orientation. Growth media was perfused through each chip at periodic intervals while the temperature was maintained at 36° C. overnight. The next day, each chip was returned to the Beacon, flushed with appropriate growth media containing DAPI dye, and incubated at 36° C. for 15 min. FOV images for both chips were again captured in BF, DAPI, and FITC cubes. Images were then analyzed and the number of pens scored for DAPI+/− as an indication of overall survival post OEP loading. The results (400% increase in 18 hour on-chip survival) are shown in  FIG. 8A . 
     Normal donor human T cells were transduced with a GFP lentiviral construct encoding a TCR specific for an investigational cancer antigen. T cell cultures were expanded in Xuri bioreactors (GE) for 10 days, analyzed via FACS to confirm expression of the transduced TCR, and frozen down for long term storage in LN2. Vials containing transduced T cells (TCR T) were thawed, cultured in G-Rex plates (Wilson Wolf) at 36° C., 5% CO2 for greater than 3 days prior to being loaded onto the Berkeley Lights Beacon. T2 cells were transduced with an mCherry construct and cultured in 6-well culture plates (Corning) for greater than 2 weeks using culture media containing human AB serum and an antibiotic selection marker. OS3500 chips were prepared for loading under the different temperature conditions as previously described in the 18 hour survival study, above. T2-Red cells were pulsed with 10 uM of the TCR T specific peptide, stained with DAPI dye and manually loaded onto each OS3500 nest and penned via gravity. Briefly, the chips were removed from the nest hardware, held at a 90 degree angle inside the cabinet of the Beacon for 15 minutes, then returned to the Beacon where the excess unpenned T2-Red cells were washed to waste. After T2-Red loading, FOV images using BF, DAPI, and TRED cubes were acquired. Next, TCR T cells were stained with DAPI and manually loaded into 2 OS3500 chips as before. The claimed device was installed over one of the chips and the temperature was lowered to 10.5° C. OEP was performed on both chips using TPS and selecting for GFP+/DAPI− TCR T cells. Excess unpenned TCR T cells were flushed to waste and images taken in BF, DAPI, TRED, and FITC across all FOV of both chips. Both chips were then removed from the Beacon as cultured on the Culture Station as previously described. 96 hours after loading, each chip was returned to the Beacon, flushed with growth media containing DAPI dye, and imaged on the Beacon in the BF, DAPI, TRED, and FITC cube channels. Proliferation was scored by counting nanopens with no more than 2 cells DAPI−/GFP+ at the time of load and no less than 4 DAPI−/GFP+ TCR T cells at 96 hours. The results (241% increase in antigen-specific proliferation after 96 hours) are shown in  FIG. 8B . 
     Further, while several examples have been disclosed herein, any features from any examples may be combined with or replaced by other features from other examples. Moreover, while several examples have been disclosed herein, changes may be made to the disclosed examples without departing from the scope of the claims.