SYSTEM AND METHOD FOR IMAGING AND ILLUMINATION FOR CELL CONFLUENCE MEASUREMENT

A cell monitoring plate comprises a flat surface on which multiple cell culturing vessels may be stacked. The flats surface has multiple optical imaging systems embedded therein to fully image a cell culture vessels stacked on the plate. Each one of the multiple optical imaging systems provides both illumination and imaging through a single aperture in the surface of the monitoring plate.

FIELD OF THE INVENTION

This invention pertains to the field of laboratory work, and, in particular, to the equipment and methods used in a laboratory environment for imaging of microscopic structures such as cells. More particularly, the present disclosure relates to systems and methods for measurement of cell culture confluence.

BACKGROUND OF THE INVENTION

Cell culture is an indispensable tool that has found many important and valuable applications in a wide range of areas such as drug screening, toxicity testing, genetic engineering, therapeutic protein and vaccine production. In general, mammalian cell lines are cultured in an incubator, where it is beneficial to closely monitor and control temperature, humidity and CO2content. During the cell culture processes, the cells seeded in a culture vessel filled with culture media must be monitored as they grow before being processed in downstream processes.

For example, cell confluency of cell culture may be monitored. Generally, cells are subcultured or passaged when they reach 80%-90% confluency because cells could lose their proliferating and gene expression phenotype when they become overgrown. In addition to cell confluency, a wide range of other important applications such as cell migration tracking, cell density measurement, and total cell number estimation also require frequent observation.

To visualize confluency, a bench top light microscope is typically used. Cell culture vessels containing both cells and cell culture media are taken out of the cell incubator and placed on a specimen stage of a light microscope. Researchers observe the cells in a bright field mode through the ocular lens (eyepiece) of the microscope. Cell confluency is often measured by counting cells, which can be a tedious and error-prone process.

The method of observation with a bench top light microscope has several major drawbacks. For example, researchers have to frequently manually take cell culture vessels out of the cell incubator. This procedure may interfere with the cell culture process. When cell culture vessels are removed from the cell incubator, the cells experience an environment change including temperature, atmosphere and humidity. Furthermore, there exists potential that the cell culture gets contaminated due to frequent contact of cell culture vessels with incompletely sterilized labware outside of the cell incubator. The contamination of cell cultures with microorganisms (bacteria, fungi, yeast, etc.) can change the biochemical and biophysical behaviors of cells, or even cause the death of cells.

Thus, there is a desire and need to monitor cells without having to physically move the cell culture vessels from the incubator environment to a microscope. One significant problem is that the illumination required for viewing these cells with high contrast must come from behind the cells, that is, a back illumination that transmits through the cells and then enters the objective lens of the microscope. This becomes challenging if the optical imaging system and the illumination system are physically located in different places in the stack. It would be very beneficial to have the imaging and illumination channels in the same area of the stack to make modifications to the tray stacks and alignment between the channels easier.

SUMMARY OF THE INVENTION

Disclosed herein is a system and method for imaging cells in trays with illumination and imaging systems that sit side-by-side but still allow for back illumination of the cells. The imaging and illumination system is compact and functional and can be used with cell growth trays.

The invention includes at least one transparent tray for growing living cells, a second tray stacked on top of the first tray, an imaging system for forming an image of an area in the tray where cells are growing, an illumination system for back illuminating the cells in transmission. The imaging system includes a lens system, a telecentric aperture stop, and an image sensor. The illumination system includes a light source for generating a light within a spectral band and a lens for creating a collimated image of the light source, wherein the collimated image of the source passes through the surface of the tray that the cells are growing on at an oblique angle and reflects off the second tray surface to back illuminate the cells on the first tray surface and wherein this back illuminated light then enters the imaging system and the image of the source is re-imaged by the imaging system lens into the telecentric stop and the image of the cells is created on the image sensor.

It is an object of this invention that the optical axis of the illumination system is reflected into the optical axis of the imaging system by a tray surface above the object tray. This allows the illumination system to be next to the imaging system and yet still illuminate the object cells from behind. This configuration requires the plane of the cells to be at an oblique angle to the optical axis of both the illumination and the imaging systems. Thus, the image plane created by the imaging system lens is tilted at an angle to the optical axis. This creates a focus shift across the field of view unless the image sensor is tilted to compensate this by satisfying the Scheimpflug condition.

Integrating the invention into a stand-alone monitoring plate can allow the use of the system with industry standard cell culturing vessels. The invention has an advantage because the illumination system and the imaging system are next to each other and, as such, can be installed as a monolithic apparatus. They can be pre-aligned to each other and take up minimal space in the cell growth trays. Any space taken up by a camera system is space that cannot be used for cell growth. This minimizes the space and creates an image of the cells by rear illumination.

DEFINITIONS

The terms “confluence” and “confluency”, as used herein, refer to the proportion of a cell culture substrate surface occupied by cells.

As used herein, “have,” “having,” “include,” “including,” “comprise,” “comprising” or the like are used in their open-ended sense, and generally mean “including, but not limited to.”

The singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. The endpoints of all ranges reciting the same characteristic are independently combinable and inclusive of the recited endpoint. All references are incorporated herein by reference.

The terms “top”, “bottom”, “side”, “upper”, “lower”, “above”, “below” and the like are used herein for descriptive purposes and not necessarily for describing permanent relative positions. It should be understood that the terms so used are interchangeable under appropriate circumstances such that embodiments of the present disclosure are, for example, capable of operation in other orientations than those illustrated or otherwise described herein.

DETAILED DESCRIPTION

Reference will now be made in detail to the present embodiment(s), an example(s) of which is/are illustrated in the accompanying drawings. Whenever possible, the same reference numerals will be used throughout the drawings to refer to the same or like parts.

All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. Any definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.

The present disclosure is described below, at first generally, then in detail on the basis of several exemplary embodiments. The features shown in combination with one another in the individual exemplary embodiments do not all have to be realized. In particular, individual features may also be omitted or combined in some other way with other features shown of the same exemplary embodiment or else of other exemplary embodiments.

The invention comprises an illumination and imaging system to view cells growing on a flat tray bottom. When viewing an object that is transparent, it can be difficult to see any contrast in the edges of the cell. One method that works well is to illuminate the cells from behind and direct the illumination source to enter and underfill the entrance pupil of the objective lens of the imaging system.

Embodiments of this invention provide the benefit of positioning the imaging and illumination channels on the same side of the cells being imaged. Thus, the imaging and illumination channels can be located in the same area of the cell culture stack, making modifications to the tray stacks and alignment between the channels easier. In addition, embodiments of this invention offer compact imaging solutions that allow cell culture vessels to remain in-place for imaging, eliminating the need to relocate a cell culture vessel from an incubator environment to an imaging platform. Such relocation of the vessel is not desirable as it can disturb the cells, change the environmental conditions of the cells, thereby negatively impact the resulting cell culture.

Embodiments of the present disclosure relate to a compact optical imaging system for cell culture monitoring built into a monitoring plate on which multiple cell culture trays may be stacked. The monitoring plate includes a plurality of detectors and illumination sources. A collimating lens is positioned between a surface of a cell culture vessel and the illumination source, wherein the illumination source is configured to emit light at an angle oblique to the surface of the cell culture vessel. The detector has a related lens positioned between the surface of the cell culture vessel and the detector, wherein the lens focuses light to the detector through an aperture stop, and wherein the detector is configured to receive light exiting the surface of the cell culture vessel at an angle oblique to the surface.

The system is configured to be operated in bright field mode, which allows for various aspects of cell culture health to be determined through image analysis of a bright field image. Additionally, systems as described herein have a small footprint that permits the system to be integrated into, or removably associated with, a cell culture vessel in a way that allows for continuous monitoring of cell culture status using a bright field mode.

FIG. 1schematically illustrates one of the plurality of detector/illumination source from a monitoring plate. It should be appreciated that the schematic illustration ofFIG. 1is not drawn to scale. As shown, the compact optical imaging system100includes an illumination source10and a collimating lens20. The illumination source10is oriented to emit light that is collimated by the collimating lens20and directed toward a first surface50of a cell culture vessel30. The illumination source10may be, for example but not limited to, a light emitting diode (LED) or an array of LEDs. Alternatively, the illumination source10may be a non-LED light source, such as an incandescent, compact fluorescent (CFL), halogen, or other source configured to produce and emit a beam of light. The illumination source10may produce a white light or a colored light of any wavelength or combination of wavelengths in the visible spectrum.

As further shown inFIG. 1, the optical imaging system100includes a detector80. The detector80includes an image sensor for detecting light impinging on the image sensor and converting the light into an electrical signal. The image sensor may be a charge-coupled device (CCD) sensor, a complementary metal oxide semiconductor (CMOS) sensor, or any other type of sensor that is capable of converting light into an electrical signal. Alternatively, the detector80may simply include a CCD, CMOS, or other image sensor. The system100further includes a lens60for collecting light and an aperture stop70disposed between the first surface50of the cell culture vessel30and the detector80, wherein the lens60collects light and focuses the light through the aperture stop70and onto the detector80.

According to embodiments of the present disclosure, the illumination source10, collimating lens20, and any other optical components in the path of the light emitted from the illumination source10are positioned to transmit the light such that the direction of the light beam as it enters the cell culture vessel100is at an angle oblique to the first surface50. Similarly, the detector80is positioned at an angle to receive light exiting the first surface50of the cell culture vessel100at an angle that is oblique to the surface50(i.e., neither parallel to or at a right angle to surface50). In operation, a light beam is emitted from the illumination source10in the direction of the first surface50of the cell culture vessel30, wherein the first surface50contains live cells to be imaged. The light beam travels into and through a cell culture vessel90of the cell culture vessel30, contacts a second surface40of the cell culture vessel30positioned on an opposite side of the cell culture vessel90, and is redirected at an angle in the direction of the detector80. After being redirected, the light passes through cells on the first surface50of the cell culture vessel30before being focused by lens60to the aperture stop70. The image of the illumination source10is created at the aperture stop70such that the source image underfills the aperture size. When underfilling the telecentric stop, the appropriate contrast of the imaged cells is generated so that they can be viewed clearly. The image of the illumination source is conjugate to the aperture stop.

As shown, the illumination source10and the detector80are configured to be positioned on the same side of the first surface50of the cell culture vessel30. This configuration allows for the system100to operate in a bright field mode, thus backlighting the cells to be imaged. In a bright field mode, light from an illumination source enters an imaging objective lens assembly directly, and viewed objects absorb, change the phase of, or redirect some of the transmitted light such that the sample appears dark on a bright background. When operated in bright field mode, the system100allows for various aspects of cell culture health to be determined through image analysis of a bright field image, including, but not limited to, cell count, cell confluency, cell density, and cell migration tracking.

FIG. 2illustrates an example of the optical imaging system100, according to embodiments of this disclosure, for imaging cells in a multi-layered cell culture vessel31, or in a stack of cell culture vessels. Components of the optical imaging system100correspond to those of like reference numerals inFIG. 1. The multi-layered cell culture vessel31includes a first cell culture vessel90ahaving a first surface50aand a second surface40aon an opposite side of the first cell culture vessel90afrom the first surface50a. The multi-layered cell culture vessel31further includes a second cell culture vessel90bhaving a first surface50band a second surface40bon an opposite side of the cell culture vessel90bfrom the first surface50b. The compact optical imaging system100operates similarly as described above with reference to the single-layered cell culture vessel as shown inFIG. 1. However, in the multi-layered cell culture vessel31, the optical imaging system100can be arranged so that a light beam from the illumination source10can be redirected from the further (?) second surface40bof the second cell culture vessel90btoward the detection system.

According to embodiments of this disclosure, the cells to be imaged in a multi-layered cell culture vessel, such as the one shown inFIG. 2, for example, can be imaged using illumination that is redirected from a surface of a cell culture vessel other than the cell culture vessel containing the imaged cells. While the multi-layered cell culture vessel31ofFIG. 2only shows two cell culture vessels90a,90b, it is contemplated that embodiments of the compact optical imaging system can be used in multi-layered cell culture vessels having variety of numbers of layers or cell culture vessels. The light beam from the illumination source of the optical system can therefore be redirected by a surface of the cell culture vessel immediately above the cell culture vessel containing the cells to be imaged, or the light beam may be directed by a cell culture vessel that is two or more levels above the cell culture vessel containing the cells to be imaged. Further, the surface used to redirect the light beam from the illumination source can be a bottom surface (e.g., first surface50b) of a cell culture vessel, or a top surface (e.g., second surface40b) of a cell culture vessel.

In some embodiments each cell culture vessel can have a bottom surface upon which the cell culture rests. In such cases, the bottom surface of the next higher tray in the stack may act as the top for the vessel immediately below it and may be used to redirect light back into the cell culture. Alternatively, each cell culture vessel may have a cover which may serve as the surface from which the light is redirected into the cell culture. It is contemplated that each cell culture vessel (i.e. each layer in the stack) will contain only one cell culture.

FIG. 3shows an illustration of a monitoring plate300in accordance with an embodiment of the invention. The monitoring plate300shown is equipped with five optical imaging systems labeled 1-5. Each of the five apertures302shown inFIG. 3services one optical imaging system100, acting as an aperture for both transmission of the light source to the culture and collection of the image. Although the illustration ofFIG. 3shows five optical imaging systems100, it would be realized by one of skill in the art that any number of optical imaging systems100can be used and that the multiple optical imaging systems100can be arranged in any way such as to provide coverage of the entire, or at least a majority of a cell culture vessel.

FIG. 4shows monitoring plate300ofFIG. 3having the top removed to show the relative size and positioning of each optical imaging system100with respect to the interior of monitoring plate300. Once again, the arrangement in number of optical imaging systems shown inFIG. 4is exemplary in nature.

In addition to the multiple optical imaging systems100, monitoring plate300may contain additional components, as shown in View (A) ofFIG. 5. In addition to multiple optical imaging systems100, monitoring plate300may include a controller component304for controlling the overall operation of the other components within monitoring plate300. Monitoring plate300may be equipped with a communications interface306sending images collected by the multiple optical imaging systems100off unit for processing. Communications interface may be a wired connection or may be a wireless connection, for example, Wi-Fi or Bluetooth. Controller component304may receive commends via communication interface306to initiate imaging of the cell cultures. Monitoring plate300will also require a power source to power the controller304, the communications interface306and the multiple optical imaging systems100. Power source308may comprise a battery, a rechargeable battery or an external power source accessible via a power source interface. Monitoring plate300may also optionally include imaging processing component310, which may optionally process the images collected by multiple imaging systems100. In such a case, communications interface306would communicate the results of the image processing off unit in lieu of or in addition to transmitting the actual images off unit. Image processing component310may include one or more machine learning models trained to determine cell confluence based on images of cell cultures, or other means to determine cell confluence from images. View (B) ofFIG. 5shows one possible layout of the components shown in View (A) in the interior of monitoring plate300.

FIG. 6shows one embodiment of a layout of the imaging portion of a single optical imaging system100. The cells sit on the surface of the tray at the cell plane602and light from them is imaged by a lens604. The image is formed at the camera plane606where the sensor resides. A telecentric aperture stop is placed at the rear focal point of the lens to ensure that the angular distribution of light across the images the same. Fold mirror608allows the optical imaging system100to be offset from and orthogonal to the aperture302in monitoring plate300.

FIG. 7shows one possible embodiment of a hardware configuration for containing the illumination component702and the imaging component704. The illumination component702could be positioned above the imaging channel704at the expense of additional space in the stack of trays. However,FIG. 8shows an embodiment which allows the illumination component702and the imaging component704to be kept in the same plane. InFIG. 8, the tubes containing the illumination component702and the imaging component704are rotated (or clocked) such that the illumination light passes through the cell tray and strikes another tray surface at an angle. This light then reflects off the tray surface and illuminates the cells from behind. Note that the plane that the cells are on is at an oblique angle to the optical axis of the imaging system. Illumination component702and imaging component704may be housed as a single optical imaging system100as shown inFIG. 4. It is contemplated that both illumination component702and imaging component704will both share aperture302defined in monitoring plate300.

FIG. 9shows an alternate embodiment for delivering the angled illumination. As shown inFIG. 9, the LED light source902is offset from the axis of the illumination optic904. The amount of offset sets the illumination angle.

FIG. 10shows several views of monitoring plate300showing one of the multiple optical imaging systems100positioned therein. View (A) ofFIG. 10shows a cutaway perspective view showing a single aperture302shared by illumination component702and imaging component704. View (B) shows a side view of monitoring plate300showing that the arrangement of optical components previously describes allows the maintenance of the thin aspect ratio of monitoring plate300. Also shown in View (B) is post1002protruding from the top surface of monitoring plate300. Post1002allows the alignment of a cell culture vessel, for example, the cell culture vessel1102shown in View (A) ofFIG. 11, with monitoring plate300and as such, with multiple optical imaging systems100. View (C) shows a single aperture302defined in the service of monitoring plate300being shared by both imaging component704and illumination component702.

FIG. 11, Views(A,B) are illustrations of several commercially-available cell culture vessels1102stacked one on top of another to form stack1104, suitable for use with monitoring plate300.FIG. 12shows one embodiment of a method by which the trays1102may be aligned with each other by providing interface feature1202. It should be noted that the interface feature1202shown inFIG. 12is exemplary only and that any means of aligning the cell culture vessels1102one on top of the other is contemplated to be within the scope of the invention.FIG. 13shows a stack of cell culture vessels1104about to be placed on monitoring plate304imaging.

In one embodiment of the invention, it is contemplated that only the bottom cell culture vessel1102of stack1104will be imaged. In such a case, the optical parameters of each optical imaging system100, for example, the focal length of imaging component704, may be preset such as to be focused only on the bottom most layer of stack1104. Thereafter, it may be assumed that upper layers of stack1104will contain cultures having similar characteristics to the culture in the bottom most layer. In such a case, the results for the upper layers of stack1104may be interpolated based on the measurement of the bottom most layer.

In alternate embodiments, is contemplated that optical imaging systems100will be able to refocus such as to be focused on upper layers of stack1104. In such a case, the optical parameters, including the focal length of imaging component704may need to be adjusted to be focused on a particular layer within stack104. The components comprising imaging component704and illumination component702may be moved via mechanical means, for example, servos or MEMS components. In alternate embodiments, the components may be dynamically configurable to change their characteristics in a non-mechanical manner. In addition, to image multiple layers in stack1104will be necessary that illumination component be capable of illuminating specific layers, which means that the source of illumination must be capable of illuminating the layers through one or more layers of cultures below the layer being image. In such cases, it is contemplated that illumination source may be, for example, a laser's light source, a infrared light source, or a wide spectrum light source having a high-intensity.

As one non-limiting example of the invention, the optical imaging systems100may be configured as described inFIG. 1orFIG. 2such that the direction of the light beam emitted by the illumination component702enters a cell culture vessel of a cell culture layer1102positioned above monitoring plate300at an angle oblique to the surface of the cell culture layer1102. Similarly, the imaging component704of the optical imaging system100is positioned at an oblique angle relative to the direction of the light beam being received by the optical sensor from the cell culture layer1102. The direction of the light beam is also at an angle that is oblique to the surface of the cell culture layer1102as it passes through the area of the cell culture layer1102where the cells being imaged are located. Because the light passes through the surface of the cell culture vessel at an oblique angle, the light beam is also at an oblique angle relative to the cells adhered to that surface. This will result in a focus shift across the field of view if the image sensor is perpendicular to the light beam. Thus, the image sensor can be positioned at an oblique angle relative to the light beam so that the cells can be imaging in focus across the field of view, in accordance with the Scheimpflug principle. In operation of the optical imaging system100, a light beam is emitted from the illumination component702positioned in monitoring plate300in the direction of the cell culture layer1102positioned above monitoring plate300, wherein a first surface of the cell culture layer1102contains live cells to be imaged. The light beam travels into and through the cell culture layer1102, contacts the bottom surface of the cell culture layer1102positioned directly above the cell culture layer1102being imaged, and is redirected at an angle in the direction of the image sensor positioned in the monitoring plate300. After being redirected, the light passes through cells on the first surface of the cell culture layer1102and is focused to the image sensor.

The images obtained from multiple imaging systems100may be processed to determine the confluence of the cell cultures contained in cell culture layers1102.FIG. 14shows a system for making the determination of the cell confluence. Multiple images from multiple stacks1104of cell cultures to be received by system1402. Analytics component1402may analyze the images using analytics1404to approximate a value for the cell confluence exhibited by each layer1102in stacks1104. Analytics1404may comprise, for example, one or more machine learning databases trained to approximate confluence. In alternative embodiments, other forms of analytics may be used. Analytics1404may utilize database1406in support of the effort to analyze the images. Database1406may contain, for example, the machine learning models used to analyze the images. Results of the analysis from analytics1404may be output on one or more dashboard clients1408which may present the results in a variety of different ways.

The analytics component1402may be embodied as hardware accompanied by a processor executing instructions from a non-volatile, computer-readable medium. A computing architecture suitable for use in support of the systems and apparatuses is shown inFIG. 15, which illustrates an embodiment of an exemplary computing architecture1500suitable for implementing the various embodiments as previously described. In one embodiment, the computing architecture1500may, in whole or in part, comprise or be implemented as part of an electronic device, such as a computer, smartphone or tablet computing device1550. The embodiments are not limited in this context.

The computing architecture1500includes various common computing elements, such as one or more processors, multi-core processors, co-processors, memory units, chipsets, controllers, peripherals, interfaces, oscillators, timing devices, video cards, audio cards, multimedia input/output (I/O) components, power supplies, and so forth, all of which are able to communicate as necessary using appropriate connections. The embodiments, however, are not limited to implementation by the computing architecture1500.

As shown inFIG. 15, the computing architecture1500comprises computer1550comprising a processor1502, and a system memory1504. The processor1502can be any of various commercially available processors. Dual microprocessors, multi-core processors, and other multi-processor architectures may also be employed as processor1502.

An interface is provided for system components including, but not limited to, the system memory1504to the processing unit1502. The interface can be any of several types of bus structure that may further interconnect to a memory bus (with or without a memory controller), a peripheral bus, and a local bus using any of a variety of commercially available bus architectures. Interface adapters may connect to the system bus1206via a slot architecture. Example slot architectures may include without limitation Accelerated Graphics Port (AGP), Card Bus, (Extended) Industry Standard Architecture ((E)ISA), Micro Channel Architecture (MCA), NuBus, Peripheral Component Interconnect (Extended) (PCI(X)), PCI Express, Personal Computer Memory Card International Association (PCMCIA), and the like.

The drives and associated computer-readable media provide volatile and/or nonvolatile storage of an operating system1520, applications1522, and related data and data structures1524. Applications1522may be in the form of software comprising computer-executable instructions. In one embodiment, the one or more applications1522and data1524may comprise, for example, the analytics component1402described above and used to analyze images received from one or more monitoring plates300.

A user can enter commands and information into the computer1550through one or more wire/wireless input devices, for example, a keyboard1510and a pointing device, such as a mouse1512. Other devices1514may include, for example, monitoring plate300, or a smart incubator. Other types of user input devices1514may include, for example, microphones, infra-red (IR) remote controls, radio-frequency (RF) remote controls, game pads, electronic pencils, card readers, dongles, finger print readers, gloves, graphics tablets, joysticks, keyboards, retina readers, touch screens (e.g., capacitive, resistive, etc.), trackballs, trackpads, sensors, projectors, lasers scanners and the like. These and other input and output devices are often connected to computer850via various means, including serial ports, USB connections, wired network connections, Wi-Fi connections, Bluetooth connections, etc.

A monitor1508or other type of display device may be used to provide video output222to a user. The monitor1508may be internal or external to the computer1550. Monitor1508may act as both a display device and as an input device, as in the case of a touch-screen display commonly found on smartphones and tablet computing devices. In addition to the monitor1508, a computer typically includes other peripheral output devices, such as speakers, printers, and so forth which may be used to provide audio outputs224.

The computer1550may operate in a networked environment using logical connections via wire and/or wireless communications to one or more remote, networked computers, such as monitoring plates300. The networked computer can be a workstation, a server computer, a router, a personal computer, portable computer, microprocessor-based entertainment appliance, a peer device or other common network node, and typically includes many or all of the elements described relative to the computer1550. The logical connection depicted includes connectivity to a local area network (LAN) or wide area network (WAN)110. Such LAN and WAN networking environments are commonplace in offices and companies, and facilitate enterprise-wide computer networks, such as intranets, all of which may connect to a global communications network, for example, the Internet. Computer1550may be connected to the LAN/WAN110via a wired or wireless communication network interface or adaptor1516. Network adapter1516can facilitate wired or wireless communications to the LAN/WAN110, which may also include a wireless access point disposed thereon for communicating with the wireless functionality of the network adaptor1516.

A monitoring plate300having multiple integrated optical imaging systems100for imaging one or more layers of cull culture vessels1102has been described herein. In addition, an analytics component1402for analyzing images received from one or more monitoring plates300and for estimating the cell confluence of cell cultures contained in one or more layers of cull culture vessels1102, as well as the computing architecture1500sufficient to support the analytics component1402, have been described herein. Exemplary physical and logical components and arrangements of components have been used in the description of the monitoring plate300and analytics component1402, however, as will be realized by one of skill in the art, many different arrangements of the physical and logical components, or substitutions therefor, may be used without deviating from the intended scope of the invention. For example, different configurations of illumination component702and imaging component704are within the scope of the invention.