Patent Description:
In a typical optical microscope, light passing through a sample is delivered to the eye of a user, a film, or a sensor through lenses, which then forms an image that is representative of the sample.

In other approaches, light representative of a sample can be detected and used to form an image of the sample without lenses by placing the sample on or near a detector, for example, an integrated circuit, that includes an arrangement of light sensitive elements. Signals generated by the detector can be processed to derive an image.

<CIT> describes an imaging device that includes light sensitive locations. A chamber lid can be suspended by attaching it at an aperture in a balloon having a closed shape. The balloon provides a tension pulling down on the lid and serves as a gasket to contain a fluid sample.

The invention is defined in the claims. In one aspect, an apparatus comprises a solid member of transparent material; a light sensitive imaging sensor; a deformable member coupling the solid member to a surface including the light sensitive imaging sensor, the deformable member comprising sidewalls enclosing a fluid chamber configured to receive a volume of fluid, the fluid chamber comprising an inlet port and an outlet port, the light sensitive imaging sensor exposed within the fluid chamber, the height of the fluid chamber being dependent on a position of the solid member with respect to the light sensitive imaging sensor; and a pressurizable chamber distinct from the fluid chamber, enclosing a liquid or gas impinging on an exterior of the fluid chamber, and configured to deform the deformable member to cause adjustment to a height of the fluid chamber, the pressurizable chamber comprising an aperture through which a fluid under pressure can be applied.

In some implementations, the solid member is coupled to the deformable member, the height of the fluid chamber being dependent on a position of the solid member with respect to the light sensitive imaging sensor.

In some implementations, the solid member comprises a plate and a protruding element, optionally wherein the shape of the protruding element comprises a truncated pyramid.

In some implementations, the solid member comprises a flat surface facing a surface of the light sensitive imaging sensor, optionally wherein the light sensitive imaging sensor is fixed and the deformable member allows the solid member to be moved in reference to the light sensitive imaging sensor.

In some implementations, the deformable member and the solid member are configured to maintain a surface of the solid member parallel to a surface of the light sensitive imaging sensor.

In some implementations, a surface of the solid member comprises a hydrophilic coating.

In some implementations, the pressurizable chamber encloses the fluid chamber and comprises a transparent roof, optionally wherein a base of the fluid chamber comprises an integrated circuit board.

In some implementations, the apparatus comprises a device coupler to couple electronically to a mobile device capable of accepting electronic communications corresponding to signals derived from the light sensitive imaging sensor, and a housing to hold the light sensitive imaging sensor, the deformable member, the pressurizable chamber, and the device coupler.

In some implementations, the fluid chamber comprises an inlet port and an outlet port, and/or wherein the fluid chamber and the outlet port are configured so that a decrease in the height of the fluid chamber causes fluid to flow out of the fluid chamber.

In some implementations, the pressurizable chamber comprises an aperture through which a fluid under pressure can be applied.

In some implementations, a surface of the light sensitive imaging sensor comprises a hydrophilic coating.

In another aspect a method comprises: injecting a fluid sample into a fluid chamber comprising an inlet port and an outlet port; adjusting a volume of liquid or gas in a pressurizable chamber distinct from the fluid chamber, the pressurizable chamber comprising an aperture through which pressure may be applied, the volume of liquid or gas impinging against an exterior of the fluid chamber to deform a deformable member to reduce a volume of the fluid chamber to cause a reduction of volume of the fluid sample, the deformable member comprising sidewalls enclosing the fluid chamber, wherein a solid member of transparent material is affixed to the sidewalls, the height of the fluid chamber being dependent on a position of the solid member with respect to a light sensitive imaging sensor within the fluid chamber; and after reducing the volume of the fluid sample, capturing an image of a portion of the fluid sample at the light-sensitive sensor surface.

In some implementations, the method comprises adjusting a volume of liquid or gas in the pressurizable chamber to increase the volume of the fluid chamber, optionally wherein the pressurizable chamber encloses the fluid chamber.

In some implementations, adjusting the volume of liquid or gas comprises altering a force applied against the fluid chamber, and/or wherein reducing the volume of the fluid chamber comprises reducing the height of the fluid chamber to allow only a monolayer of the fluid sample to remain in the fluid chamber.

In some implementations, the fluid sample comprises blood, and optionally the method comprises performing a blood count of the fluid sample based on the captured image.

Unless otherwise defined, all technical and scientific terms used here have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described here can be used in the practice or testing of the present invention, suitable methods and materials are described below. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

Other potential features and advantages will become apparent from the description, the drawings, and the claims.

Images captured using contact microscopy often require a well-defined surface of contact between a light sensitive sensor surface and particles to be analyzed. For quantitative techniquesthe ability to compute an accurate particle count within a fluid sample is based on forming a thin layer of uniformly distributed sample over the sensor surface where the height of the thin layer is roughly the diameter of the particles (for example, a monolayer). However, due to a variety of complexities within microenvironments (e.g., fluid-surface interactions, lack of sufficient precision in adjusting the placement of physical components), establishing and maintaining the layer of uniformly distributed sample prior to conducting an imaging procedure is often difficult, complicating efforts to repeat accurately the use of similar techniques in subsequent imaging procedures.

One field where contact microscopy techniques can be applied is for performing blood counts where cells or cellular components such as red blood cells and platelets are counted in a carefully controlled volume of blood. Blood counts can be useful in diagnosing pathologies and health conditions, determining severities associated with such diagnoses, and monitoring changes in diseased conditions of patients.

However, while such technologies are ubiquitous in the health care systems of developed countries, their application has been limited in the developing world. For instance, blood counts can be expensive to administer, and tend to be performed on dedicated machines operated in dedicated labs, for example, in hospitals or clinics, which hampers their use in resource-limited or remote locations where the lack of skilled operators often preclude the use of large-scale technologies with a relatively high complexity.

Accordingly, innovative aspects described throughout this specification relate to improving sample processing for contact microscopy techniques used to compute blood counts, among other applications. The systems and techniques described here provide a cost-effective means to improve the repeatability and accuracy of performing blood counts. For instance, structures of the systems can be designed to enhance techniques that are directed to establishing and maintaining a uniformly distributed thin sample layer over a sensor surface to consistently compute a cell count. The figures and elements shown in them are not always to scale and many of them are illustrated schematically. The spatial relationships of the elements in the figure may appear differently than the descriptions in the text, for example, above and below and top and bottom may be shown oppositely in the figures from the way they are described in the text.

As described here, "light sensitive locations" include, for example, any features of a device that are separately sensitive to light or separately capable of emitting light, or both, including light sensitive elements or pixels and light source locations. The phrase light source locations can refer to elements capable of emitting light. In some cases, the phrase light sensitive location can refer to an exposed light sensitive portion of a feature of the device without any covering, protective layer, shield, or any other feature that might separate the light sensitive from the ambient or from a sample.

As described here, "contact microscope" or "contact microscopy" refers to any imaging device or technique that includes a light-sensitive sensor in contact with a sample to be image. For example, a contract microscope may include: (a) a high resolution sensor of closely spaced light sensitive or a high resolution set of light emitting locations that are exposed to the ambient at a surface of the device together with (b) a device to associate with that surface a portion of a sample that is to be imaged, and, in the case of light emitting locations, a light detector relatively far from the light emitting locations and sample, so that the portion of the sample is in contact with (or nearly in contact with) the surface and a usable high resolution image can be obtained by the sensor when the portion of the sample is in place.

As described here, a "sensor" refers to an integrated circuit, or a component of an integrated circuit that includes a light-sensitive element. For example, a sensor can be a component that receives light at the light sensitive elements and generates signals or data representing the intensities of light detected by the light sensitive elements, and processes any electronic elements that directly drive the light sensitive elements or cause the light-generated signals or data to be delivered by the light sensitive elements.

As described here, "parallel" arrangement of surfaces may include a substantially parallel arrangement between a chamber top and a surface of the light sensitive sensor such that the arrangement provides a uniform distributed of particles over the surface of light sensitive sensor.

As described here, "settling" refers to placement of a surface of a body over a sample such that the body stably sinks towards the top the sample. For instance, a body can settle on top of a sample if, for example, the body is not attached to, or held in place by, a separate component. In other instances, the surface of the body may settle on top of the sample based on the body being pressed against the sample.

In contact microscopy, a sample to be analyzed is associated with light-sensitive features of a sensor in that it is, for example, in direct contact (e.g., without any intervening materials) with the light sensitive features of a sensor or the light imaging of the light source, or nearly in contact with the light sensitive or emitting features. For instance, "nearly in contact" can refer to, for example, within the near field of the light sensitive or light emitting features, which in some instances refers to being at a distance that is within ½ of the wavelength of the light involved or possibly at a distance that is within a range of wavelengths of the light involved.

In embodiments of the system and techniques that we describe here, a device or devices can be used to associate the sample with the sensor surface. Such an association can include any mechanism that facilitates the movement, flow, delivery, placement, or presentation, for example, of a portion of the sample into contact with or nearly into contact with the light sensitive locations, including any mechanism that uses mechanical, electrical, electromechanical, pneumatic, hydraulic, capillarity, surface wetting-and gravitational forces, among others.

<FIG> illustrates an example of a system <NUM> that generally includes various components used to capture high-resolution images of a sample <NUM> that is in contact with, or in close proximity to, a surface <NUM> of a light sensor <NUM>. The system <NUM> also includes a light source <NUM>, sample management devices <NUM> and <NUM>, an integrated chip <NUM>, a headboard <NUM>, a control unit <NUM>, a user device <NUM>, and a user interface <NUM>.

The light sensor <NUM> includes a two-dimensional arrangement of light sensitive elements <NUM> that can correspond to an array of pixels in the captured images. For simplicity, the elements of the light sensor <NUM> are described here as "pixels. " High resolution images can be captured using various color schemes (e.g., full-color, grayscale, black-and-white) or a combination of color schemes. In addition, the sample <NUM> can be in various phases (e.g., gas phase, liquid phase, solid phase), or a combination of such phases or other phases.

The light sensor <NUM> can also include other components, either as part of, or in addition to, the light sensitive elements <NUM> that perform various functions. For instance, the components can drive or read sensing elements and generate, process, and deliver electronic signals to the other components of the system <NUM> (e.g., headboard <NUM>, control unit <NUM>, user device <NUM>). The components of the light sensor <NUM> can also perform other functions such as receiving data transmissions from the components of the system <NUM>.

The sensor <NUM> can be a component of or formed on the integrated circuit chip <NUM>, which can be made in a homogeneous fabrication mode, a hybrid fabrication mode, or other conventional fabrication techniques. The chip <NUM> can be mounted on the headboard <NUM>, which can be part of or be connected to the control unit <NUM>.

The control unit <NUM> can be part of, or connected to, the user device <NUM>. The user device <NUM> can provide the user interface <NUM> for access by a user <NUM> to adjust and control the operations of the system <NUM>. For instance, the user device <NUM> can receive information <NUM> (e.g., commands) through the user interface <NUM> from the user <NUM>, process the received information <NUM>, and transmit the received information <NUM> to the control unit <NUM>. In addition, the control unit <NUM> can receive data <NUM> (e.g., sensor data from the light sensor <NUM>) from the headboard <NUM>, process the received data <NUM>, and transmit the received data <NUM> to user device <NUM> for display on the user interface <NUM>. In some instances, the user interface <NUM> can operate through the control unit <NUM> or the headboard <NUM>, or a combination of the various components of the system <NUM>.

The light source <NUM> can either be an external light source outside the system <NUM> (e.g., a room light) that provides ambient light for imaging, or a dedicated light source that provides specific illumination and intensity control of the light provided over the sample <NUM>. For instance, the light source <NUM> can be controlled, either by the user device <NUM>, or the control unit <NUM>, to adjust the intensity, focus, position, orientation, uniformity of illumination and/or other optical properties of the light provided over the sample <NUM>.

Since the sample <NUM> is in contact with or in close proximity to the surface <NUM> of the light sensor <NUM>, additional optical elements are not necessary to refract, collimate or redirect the light towards the light sensors <NUM> for imaging. For instance, light <NUM> from a portion <NUM> of the sample that is adjacent to a pixel (or is in a path between the incident light <NUM> and the pixel) will be received largely (in some cases essentially entirely) by that pixel <NUM>. In this arrangement, the light <NUM> sensed by the array of pixels of the light sensor <NUM> is directly representative of a corresponding array of portions of the sample <NUM> and therefore represents, in effect, a high resolution image of the sample <NUM>.

The sample transport and management devices <NUM>, <NUM> can include mechanical or electrical components, or combinations of such, that assist in loading and delivery of the sample <NUM> to a location on the surface <NUM> of the sensor <NUM> for image capture and to the formation of a thin uniform layer, such as a monolayer, a sample on the surface. For instance, the devices <NUM>, <NUM> can be used to move a container including the sample <NUM> horizontally or vertically along the surface <NUM> to position the sample <NUM> in an optical location over the sensor <NUM> and hold the container at the optical location during an imaging procedure. The devices <NUM>, <NUM>, can also process the sample before and after the imaging procedure. For example, devices <NUM>, <NUM> can be used to mix chemical reagents with the sample <NUM> during sample preparation, remove chemical reagents from the sample <NUM> for purification, fetch the sample <NUM> from an external source, dispose of an imaged sample after an imaging procedure, or any other function that may be used with respect to the sample <NUM> for an imaging procedure.

The user device <NUM> can be any type of electronic device that is capable of generating a user interface for receiving and transmitting data communications. For instance, the user device <NUM> can be a handheld device such a cell phone, a tablet computing device, or a laptop computing device, or a stationary device such as a desktop computer, or a work station. In some instances, the user device <NUM> can also be any type of instrument that is used by the user <NUM> to adjust the function of the control unit <NUM>.

As described more particularly below, the system <NUM> also includes a chamber top <NUM> (or "lid," "cover" or "chamber wall" as described here) that can abut, touch, surround, or enclose a chamber, adjacent to an exposed surface <NUM> of the light sensor <NUM> that holds a portion of the sample <NUM>. Specific descriptions related to the use of the chamber top <NUM> in relation to the operation of the system <NUM> are provided below. In some implementations, the chamber top <NUM> can be configured to be able to be lowered to contact the sample <NUM> and adjust the volume of the sample <NUM> (e.g., the volume as determined by the area of the sensor and the thickness of the sample layer atop the surface <NUM> of the light sensor <NUM>). As an example, the adjustment can be done by lowering the bottom surface of the chamber top <NUM> against the sample <NUM> such that the excessive amount of the sample <NUM> flows out horizontally along the surface <NUM> of the light sensor <NUM>. The chamber top <NUM> can also descend in other manners as described more particularly below. As described here, the space formed between the bottom surface of the chamber top <NUM> and the surface <NUM> of the light sensor <NUM> once the descent of the chamber top <NUM> is complete forms a "chamber" for the sample <NUM>. Thus, the volume of the sample <NUM> that is initially placed on top of the surface <NUM> is greater than the volume of the sample <NUM> within the chamber since, after the chamber top <NUM> initially comes into contact with the sample <NUM> and before the chamber top <NUM> reaches its final placement, excess volume of the sample <NUM> (e.g., the difference between the sample <NUM> volume introduced and the volume of the chamber) is removed from the chamber as portion of the sample <NUM> flows out of the chamber. In some instances, the excess volume of the sample <NUM> flows out laterally to the surface <NUM>. In other instances, the bottom surface of the chamber top <NUM> can be porous surface, which enables the excess volume of the sample <NUM> to flow out of the chamber through the pores of the chamber top <NUM>. In these instances, the pores may be sized such that only fluid passes through the pores but particulate matter of the sample <NUM> are too large to pass through the pores.

Although <FIG> illustrates various components of the system <NUM>, a commercial product associated with the system <NUM> need not include each of the components depicted in <FIG> and described here (and may include components other than those shown in the figure). In various implementations, any combination of two or more of the light sensor <NUM>, the chip <NUM>, the headboard <NUM>, the control unit <NUM>, and the user device <NUM> can have a variety of mechanical and electrical connections among them. In addition, mechanical, fluid flow, electronic, software, data processing, communication, storage, and electrical functions needed for various operations can be distributed in a variety of ways between and among pairs and three or more of those parts of the system. The distribution of functions can either be arbitrary or based on commercial and technological considerations in a wide variety of ways.

During operation, the light sensor <NUM> detects incident electromagnetic radiation <NUM> (or "light") that is generated from the light source <NUM> and is scattered from, or emanates from the sample <NUM>. Light that passes through, scattered from, or emanates from the sample <NUM> may be altered in wavelength, for example, as it passes through or is scattered or emanates. The incident light <NUM> and the transmitted, scattered, or emanated radiation is typically in the wavelength range of visible light, near ultraviolet, or near infrared. As described here, however, the light <NUM> can include light from all such ranges.

To capture an image of the sample, the light sensor <NUM> is driven and read during an image capture cycle. During an image capture cycle, the light <NUM> received by the light sensor <NUM> at each of its pixels is converted to electrical signals (e.g., analog signals or digital values) that are delivered to electronic components of the chip <NUM>. The signals may be read in parallel or serially depending on the components of the chip <NUM>. The electrical signal from each of the pixels is typically represented by a quantized intensity value corresponding to the intensity of light sensed by the pixel, within some range such as a range represented by, e.g., 16bit digital values.

Color information can be obtained in a variety of ways, for example, using bandpass optical filters over multiple adjacent pixels, or sequential imaging with different color illumination, among others. The electrical signals that are received from the various spatial pixels can represent a full-color high-resolution high-dynamic range image of the sample <NUM>. In addition to the electronic features of the system <NUM>, there are mechanical elements discussed below that among other things handle, contain, and illuminate the sample <NUM>.

The sample <NUM> (also referred to as "specimen" interchangeably) can be in any type of phase (e.g., liquid, solid, gas) or combination of such that is in direct contact with the surface <NUM> of the light sensor <NUM>. In some instances, the sample <NUM> is a fluid that includes various types of particulate matter such as cells (e.g., human or animal blood cells, mammalian cells, bacterial cells, and/or plant cells), molecules (e.g., DNA, RNA, peptides), proteins (e.g., antigens and antibodies), or contaminants in environmental or industrial sample. In such instances, the sample <NUM> can be dispensed into a chamber above the surface <NUM> and manipulated using the devices <NUM>, <NUM> to position the sample <NUM> over the light sensor <NUM>.

Referring to <FIG>, the sample <NUM> that is being imaged can be composed of or include small similar types of units <NUM>, such as particles, bits, specks, cells, or molecules, or combinations of them or combinations of any two or more of the different types. The units <NUM> may be suspended in or carried in a liquid <NUM> to form liquid-suspended particles <NUM>, entrained in a gas to form gas-suspended particles <NUM> (not shown), rest in an unsuspended and un-entrained form (e.g., a powder) on the surface <NUM> of the light sensor <NUM> (not shown), or be held in an integrated matrix of solid, gelled, or other integral self-supporting material such as a sectioned layer of tissue, among others. As described here, "matrix" can include, for example, any material in which particles <NUM> are held, including liquid, gas, solid, gel, or other materials.

<FIG> illustrates, for some embodiments of the system and techniques described here, a top view of the system <NUM> during a sample dispensing procedure. As depicted, a predetermined volume of the sample <NUM> is dispensed onto the surface <NUM> of the light sensor <NUM> prior to performing an imaging procedure. The volume of the sample <NUM> is dispensed using a fluid-loading pipette <NUM> using a guide <NUM> to bring the pipette tip <NUM> close to a predetermined position such that the sample <NUM> is deposited on top of the surface <NUM>.

As described more particularly below, various types of dispensing techniques can be used to deliver the volume of the sample <NUM> onto the surface <NUM>. In some instances, the fluid-loading pipette <NUM> is a specific type of pipette referred to here as a "duplex pipette. " In some instances, the fluid-loading pipette <NUM> is a conventional micropipette.

In some implementations, the chamber top <NUM> and/or the surface <NUM> of the sensor <NUM> is coated with hydrophilic coatings to enhance the capillary force and increase the speed of the sample delivery process. In some implementations, hydrophobic coatings can be used surrounding the sensor active area to contain liquid specimen. In situations when settling of the particles <NUM> is an important concern, the sample <NUM> can be mixed, e.g., during fluid ejection and/or the chamber top <NUM> descent, either or both of which can be automatically controlled, with the use of pumps, actuators, among other techniques.

<FIG> illustrate schematic diagrams of examples of the fluid-loading pipette 1040a that are referred here as duplex pipette 1040a. Referring to <FIG>, the duplex pipette 1040a includes two volumetric capillary tubes 1042a and 1042b that deliver separate input fluid streams (e.g., blood sample and diluent/chemical stain) to a mix-well chamber <NUM>, which combines the two input fluid steams into a mix-well chamber <NUM> with an aperture at other end for dispensing the mixed fluid of the two input fluid streams.

<FIG> illustrates the internal structure of the mix-well chamber <NUM>. As depicted, the left portion of the mix-well chamber <NUM> includes two receiving ports where ends of the volumetric capillary tubes 1042a-b are attached to the mix-well chamber <NUM>. The mix-well chamber can in some embodiments be detachable from the fluid containers 1042a-b such that a single mix-well chamber <NUM> can be reusable for multiple deliveries of a single sample <NUM>. The two receiving ports converge into a single channel that includes grooves <NUM> to help combine the two input fluid streams into a single output. For example, the grooves <NUM> can be arranged transverse to the fluid flow through the fluid channel such that the grooves <NUM> disturb fluid flow and enhance combination of the two input fluid streams as previously described in scientific literature. <NUM>
<NUM> <NPL>.

A wide variety of techniques and devices can be used to form and maintain a height (e.g., a precise height) of the gap <NUM>. As described here, such techniques are generally referred to as "spacing features. " In the example shown in <FIG>, the spacing feature includes microspheres or other kinds of beads of uniform size. As an example, in some implementations, the spacing features <NUM> are monodispersed rigid polymeric microspheres with a precisely defined diameter (e.g., <NUM> with a less than five percent coefficient of variation). In this example, to establish a precise and uniform spacing of the gap <NUM>, which relates to the volume of the sample <NUM> between the chamber top <NUM> and the surface <NUM>, the precision of the bead sizes can be used to ensure that gap <NUM> is repeatable in multiple imaging procedures.

In some instances, for a given kind of sample unit or a precisely specified volume of sample (e.g., for a blood count, or other analysis in which the number of particles <NUM> is to be counted for a precise volume of the sample), the volume of the sample <NUM> to be imaged is precisely controlled by the width and length of the top surface of the light sensor <NUM> and by the height of the gap <NUM> (or the chamber) between the surface <NUM> and the flat bottom surface of the chamber top <NUM>. In some instances, the volume may not need to be precise, but the gap height may need to be a precise amount, or no larger than a certain amount, or no smaller than a certain amount, or a combination of those conditions.

As shown in <FIG>, in some implementations, the spacing features <NUM> are included within the sample, for example, a sample having a liquid matrix in which particles <NUM> (which may be smaller than the beads) are suspended, when the sample is delivered to the sensor surface <NUM>. If the chamber top is then allowed to settle on or be pressed down onto the sample, and assuming that there are enough beads in the sample and they are reasonably well distributed within the liquid, then a uniform accurate gap height can be achieved. For this purpose, the beads might be present in the sample at the rate of <NUM>,<NUM> - <NUM>,<NUM> beads per microliter of sample, for example. Maintaining an even distribution of the beads in the sample can be done by simple mechanical agitation if the beads are selected to have close to neutral buoyancy in the sample.

In some cases, the beads can be roughly the same size as the particles <NUM>. In some implementations, beads of two different sizes can be included. A larger size defines the intended spacing. A smaller size can be counted to verify that the volume of the sample space is as intended, assuming the smaller beads are distributed through the sample reasonably uniformly, and the number of smaller beads per unit volume of the sample is known. The beads may be transparent in order to allow light to pass through to the sensor, or may be colored, or fluorescent, or opaque, or a combination of two or more of those characteristics.

In some implementations, instead of using spacing features <NUM> that are included within the sample <NUM>, the height of the chamber (e.g., the gap <NUM>) formed between the bottom surface of the chamber top <NUM> and surface <NUM> can instead by maintained by a set of array of pillars that protrude from the surrounding surface around the surface <NUM> (e.g., on the surface of the headboard <NUM>). In such implementations, the headboard <NUM> that houses the surface <NUM> can be specifically fabricated such that the pillars have a predetermined height corresponding the optical gap <NUM> required for a particular imaging procedure. In operation, after introduction of the sample <NUM>, the chamber top <NUM> can then be lowered onto the surface <NUM> until the bottom surface of the chamber top <NUM> comes into contact with the top surface of the pillars. Various aspects of the pillar array (e.g., array pattern, pillar density) can also be adjusted to impact the distribution of particles <NUM> along the surface <NUM>.

In some instances, the amount of sample <NUM> loaded onto the light sensor <NUM> is larger than the amounted necessary for imaging. In some implementations, the sample <NUM> needs to be in the form of a relatively thin layer, (e.g., <NUM> to <NUM>µ), or have a thickness such that a single layer of cells of the sample is displaced on the sensor for imaging. In such instance, a chamber top <NUM> can be descended to contact the sample <NUM> and adjust the volume of the sample <NUM> (e.g., the thickness of the sample layer atop the surface <NUM> of the light sensor <NUM>.

As described here, it may be desirable that the concentration of the sample <NUM> to be imaged is either the same as, or has a predetermined relationship to, the bulk concentration of the sample that is initially dispensed on the surface <NUM>. In some instances, weight of the particulate matter within the sample <NUM> (e.g., the particles <NUM> and the spacing features <NUM>) are heavier than the other fluidic components of the sample (e.g., diluent), which makes the particulate matter susceptible to accumulation as opposed to flowing or moving when an force is applied to a volume of the sample <NUM>.

One example of an external force may be gravity, which can cause sedimentation concentration gradients in the sample <NUM> as the particles <NUM> descend toward the bottom of the sample <NUM> due to a gravitational force. Another example of a force can be the force applied by the bottom surface of the chamber top <NUM> during the descent of the chamber top <NUM> as described here. In this example, the chamber top <NUM> accelerates downward, the sample <NUM> outside the perimeter of the sensor <NUM>, and the heavier suspended particles <NUM> have more momentum than the fluidic components and may not move or accelerate as quickly as the other parts of the sample <NUM>. In such an instance, the particles <NUM> may be left on the surface <NUM> of the light sensor <NUM>, leading to a higher concentration than the bulk concentration in the sample <NUM> dispensed on the surface <NUM> before the excessive volume of the sample <NUM> is removed. In yet another example, the force may also include friction force between the sample <NUM> and the various surfaces of the system (e.g., the surface <NUM>, the surface <NUM>, etc.) or a shear force generated within the sample as a result of interactions with such surfaces. The friction force and the shear force may reduce the speed of the particles <NUM> relative to the sample flow.

Additionally, after the chamber top completes its descent, the sample may continue to flow, causing the particles <NUM> to move and disrupting their imaging. In some implementations, the viscosity of the sample may be adjusted to control the concentration of the particles <NUM> and reduce the flow of the sample during imaging. In some examples, the adjustment can be done by adding one or more viscosity-controlling agents to the sample. The sedimentation rates of the particles <NUM> can be reduced and the fluid can be allowed to exert a stronger force on the spacer beads and the particles <NUM> to counter their momentum and friction. The increased viscosity also can reduce the likelihood of flow after the chamber top completes its descent. Suitable agents can include dextran, glycerol, starch, cellulose derivatives such as methyl cellulose, any combination of these materials, and other materials.

Alternatively or additionally, one or more agents can be added to the sample to increase diluent density so that the difference in density between the diluent and the spacer beads and/or the particles <NUM> is reduced or even eliminated. The reduced or eliminated density difference can also control the concentration of the particles <NUM> and reduce the flow of the sample during imaging.

The agent for increasing the diluent density can be the same agent as the viscosity-controlling agent. In some implementations, thixotropic agents can be used to achieve the same effects, and also allow for easier mixing of the particles <NUM> with the diluent. In some situations, photo-cross-linkable agent(s) or gelling agent(s) (e.g., temperature dependent, such as low-melting-point agarose) can be used to increase the sample viscosity while allowing for easy mixing of the particles <NUM> and the diluent. For example, a sample with suspended particles <NUM> and a gelling agent such as liquid agarose may initially be squeezed by the chamber top <NUM> to form a monolayer of particles <NUM> on the surface <NUM>. The temperature of the sample can be cooled to form an agarose gel structure that "traps" the particles <NUM> in their position within the monolayer, which can then be used, e.g., to perform a comet assay of DNA damage. For instance, to perform a comet assay, the sample may include a DNA-intercalating stain for detecting particles <NUM> that may be cancerous cells. In such instances, after gelling, the chamber top can be briefly raised permitting a cell lysis media to permeate the gel; a voltage gradient may subsequently be generated along the length or width of the chamber by electrodes that may also be placed on opposite ends of the chamber (e.g., on two opposite sides of the chamber top <NUM> running down to opposite edges of the truncated top surface <NUM> of the chamber top). In other instances, polyacrylamide, starch, or other gels may be used to enable rapid, inexpensive electrophoresis analysis of proteins, nucleic asides and other macromolecules. The electric field produced by the electrodes can be used to induce movements of small particles in suspension (e.g., not trapped within the gel), and such movement may be monitored using the image sensor <NUM> to measure either surface charge or zeta potential of the particles <NUM>.

Once the sample <NUM> has been dispensed on the surface <NUM> of the light sensor <NUM>, the chamber top <NUM> can be lowered towards to the surface <NUM> to remove excessive volume of sample <NUM> atop the surface <NUM> to generate a thin layer of the particles <NUM> (e.g., cells that are disbursed in a fluid sample) to be evenly distributed over the surface <NUM>. In some implementations, the removal of the excessive volume is performed in such a manner that the displacement of the excess volume does not alter the bulk concentration of the particles <NUM> above the surface <NUM> of the light sensor <NUM> so that the relatively small volume of the sample <NUM> (e.g., about <NUM> nL) that is imaged is representative of the bulk sample (e.g., about <NUM>µL or more) dispensed onto the surface <NUM> of the light sensor <NUM>. In other implementations, the removal process generates a new concentration of particles <NUM> within the relatively small volume sample of the sample <NUM> that is consistently proportional to the bulk concentration of the particles <NUM>. In such implementations, a correction factor can be determined and applied to the captured data to derive the desired sample concentration for imaging. For instance, to achieve the desired sample concentration for imaging, the sample <NUM> can be further processed using techniques described further below.

The chamber top <NUM> can be lowered in various ways as described particularly with respect to various implementations below. In the example illustrated in <FIG>, the chamber top <NUM> has a flat bottom surface <NUM> that is lowered towards the surface <NUM> such that the surface <NUM> is kept substantially parallel to the top surface <NUM> of the sensor <NUM>. As described here, this type of descent is referred to as "linear descent. " <FIG> illustrates another example where the chamber top <NUM> is initially positioned at a tilted position such that a first edge of the chamber top <NUM> is in contact with the surface <NUM> along a contact line whereas the opposite edge of the chamber top <NUM> is away from the surface <NUM>. In this configuration, the opposite edge of the chamber top <NUM> is then lowered along a rotational axis defined by the line of contact between the between the first edge of the chamber top <NUM> and the surface <NUM>. The chamber top <NUM> can be lowered at a controlled velocity profile until a point <NUM> on the bottom surface of the chamber <NUM> sits flush with the surface <NUM>. As described here, this type of descent is referred to as a "pivoting descent.

In some instances, data such as positional variables or parameters that control the descent of the chamber top <NUM> can be selectively chosen based on the type of sample <NUM> used and then stored for subsequent use. The stored data can then be accessed and automatically applied to a configuration of the system <NUM> using, for example, a controller. The descent can then be performed with sufficient repeatability for different imaging procedures based on the stored data.

In addition, the descent of the chamber top <NUM> can be controlled using various mechanisms. For example, the chamber top <NUM> can be descended manually by a human using physical means (e.g., a circular knob), or automatically with the use of a machine such as an actuator <NUM>.

In some implementations, after the first edge of the chamber top <NUM> facing away from the surface <NUM> is initially descended, corresponding points on the bottom surface of the chamber top <NUM> come into contact with the sample <NUM> throughout descent while the opposite end of the chamber top <NUM> can be raised and lowered repeatedly (e.g., without coming all the way down to a final position). This repeated motion of the chamber top <NUM> can cause the sample <NUM> to flow in and out of the space formed between the surface <NUM> and the chamber top <NUM>, which can be used to produce a mixing effect on the sample <NUM> to evenly distribute the particles <NUM> along the surface <NUM> before an imaging procedure.

In some implementations, the chamber top <NUM> has a surface <NUM> that presses against a surface <NUM> of a holder <NUM> that assists in the descent of the chamber top <NUM>. The surface <NUM> can be formed of encapsulation epoxy deposited on the surface <NUM> to form the holder <NUM>. The linear points of contact between the surface <NUM> and the surface <NUM> can then operate as a hinge for lowering or raising the chamber top <NUM>.

As an example of use, after the sample is deposited onto the surface <NUM> of the light sensor <NUM>, the chamber top <NUM> is held up at an angle by another point-of-contact <NUM> elsewhere and slid forward until the surface <NUM> is pushed against the surface <NUM> such that it cannot slide further. The hinge then allows the rotational twist of the chamber top <NUM> along its rotational axis such that the edge of the chamber top <NUM> opposite to the surface <NUM> is lowered towards the surface <NUM>. The chamber top <NUM> is then slid along the surface <NUM> until an adjacent edge of the chamber top <NUM> hits another barrier <NUM> (e.g., either also part of the encapsulation or a separate construction off to the side). This allows the positioning of the chamber top in the y-direction repeatable from test to test (or sample to sample). Then the point of contact <NUM> holding up the chamber top is lowered, allowing the chamber top to hinge down until flush with the sensor. In some implementations, the point of contact is lowered in such a way that its friction with the chamber top provides a small force that pushes the chamber top against the ridge, rather than pulling it away, to reduce or avoid disturbance to the position of the chamber top at the wall <NUM>. It is possible that the chamber top may slide after being placed on (or descended to) the sensor and when the sample is expelled from the chamber. Sometimes guide posts <NUM> and/or walls off to the side of the sensor are used to minimize the travelable distance for the chamber top.

In some implementations, the contacting edge <NUM> of the chamber top has two extending points at opposite ends <NUM> to permit the sample to flow between the points in the direction of the hinge. This may increase uniformity of sample flow in all directions out from under the descending chamber top, reducing artefactual non-uniform distribution of particles <NUM> (such as cells).

In some instances, the actuator <NUM> can be a passive device that is not fixed to the chamber top <NUM> and is used to lower the chamber top <NUM>. The chamber top <NUM> may rest on the actuator <NUM> and descend via gravity or another force (e.g., magnetism, electromagnetism, a spring). The velocity profile of the descent can be controlled by various means, such as including a rotating counterweight, a dash-pot <NUM>, magnet, electromagnet, etc..

Although the chamber top <NUM> is described to descend towards a sensor surface, the mechanisms described can be used with any surface, such as a glass slide, in implementations, such as counting cells or other particles using standard microscopy.

A particular group of applications of the system <NUM> involves analysis of a blood sample. In such applications, the system <NUM> can be used in detecting and analyzing types of cells in blood (e.g., white blood cells, red blood cells). The system <NUM> can be used for counting various types of cells, determining normality of blood cells, monitoring blood cell functions, and analyzing blood chemistry.

White blood cells (WBC) are at a relatively low concentration in blood, and the concentration can be further reduced by any dilution added to the blood in preparation of the sample. As a result the total number of white blood cells on the sensor surface to be imaged or counted can be low. Generally, the counting error for particles is the square root of the count, and a low number of particles to be counted may lead to a high percent error.

In some implementations, white blood cell concentration can be increased in a predictable manner. In some implementations, suitable spacer beads can be used such that an average concentration of red blood cells (RBC) can be maintained at a desired level on the sensor surface, while the while blood count is increased. Generally, as the chamber top <NUM> descends towards the sample, the cells that are in contact with the surface of the chamber top <NUM> and the surface <NUM> of the sensor <NUM> at opposite directions can be trapped. For example, when the cells are being compressed between the opposing surfaces, the cells generally do not move. Accordingly, the size of the spacer beads can be chosen such that the distance between the surfaces of the chamber top and the sensor is less than the average diameter of the white blood cells. In some situations, to maintain the concentration of the red blood cells, the beads can have a diameter larger than the average diameter of the red blood cells. The descending chamber top compresses the white blood cells having a diameter larger than the bead diameter without compressing the red blood cells having an average thickness smaller than the bead diameter. As the total volume of the sample is reduced with the chamber top descending to reach the bead diameter, the concentration of the white blood cells on the sensor surface increases. An example of the bead diameter can be <NUM> microns. Other suitable diameters can be selected to control the concentration of different cell types in the sample.

Once the chamber top <NUM> has been lowered to its final height, the height of the chamber (e.g., the height <NUM> illustrated in <FIG>) and the surface area of the surface <NUM> of the sensor <NUM> can be used to compute the volume of blood imaged on the surface <NUM>. The white blood cell concentration can be increased proportionally with cell size, relative to the concentration of smaller untrapped cells such as red blood cells. The relationship between the size and the concentration of the white blood cells is integrated over all the white blood cell sizes to obtain the average concentration (e.g., the bulk concentration in the sample before the cells are concentrated). This concentration effect can lead to useful improvements in counting statistics.

A wide range of products can be manufactured and delivered based on the architecture and principles that we have discussed. The products could include sensor units, sensor units plus readout units, sensor units plus headboards, sample chambers, chamber tops (or lids), sensor units plus pipettes, sensor units plus pumps, system devices, handheld devices, plugins and attachments to other equipment, pipettes, preloaded pipettes, image processors, software, light sources, sample chambers plus light sources plus sensors plus headboards plus electronics in complete devices, and combinations of two or more of these as well as other components.

In considering the wide range of operations performed by the sensors and systems and the broad spectrum of applications, it may be useful to recognize that some relate to imaging, some to analysis, and some to a combination of analysis and imaging.

The following examples of implementations of the system <NUM> use various techniques for sample loading and processing, and/or lowering a chamber top onto a sensor surface for the prior to performing an imaging procedure. As described more particularly below, each implementation provides advantages that can improve an aspect of an imaging procedure.

<FIG> illustrate perspective views of an open chamber device <NUM> that can be used for performing complete blood counts, as described throughout this disclosure, among other types of tests (e.g., biodosimetry). In this implementation, the chamber top <NUM> is lowered onto the surface <NUM> of the light sensor <NUM> with the use of a carrier arm that is lowered with the use of an actuating element. The chamber top <NUM> is initially placed on an extension tip of the carrier arm such that the chamber top <NUM> is not rigidly attached on the carrier arm but loosely attached to enable the chamber top <NUM> to settles on top of the extension tip of the carrier arm. In addition, the chamber top <NUM> is placed in such a manner that its descent is in a direction that is substantially parallel to the surface <NUM> of the light sensor <NUM>.

Referring now to <FIG> and <FIG>, the system <NUM> includes a plate <NUM> with an open specimen chamber <NUM>. The surface of the plate <NUM> includes the surface <NUM> of the light sensor <NUM>, and the headboard <NUM>. A more descriptive view of the open specimen chamber <NUM> is illustrated in <FIG>. The system <NUM> also includes a carrier arm <NUM> attached to an actuating device <NUM> and support structures <NUM> for positioning the chamber top <NUM> in a substantially parallel manner above the surface <NUM> prior to operation.

In operation, the chamber top <NUM> is initially placed above the surface <NUM> onto an extension of the carrier arm <NUM> (illustrated as the extension tip <NUM> in <FIG>). After being placed on the extension tip <NUM> of the carrier arm <NUM>, the chamber top <NUM> is also positioned parallel to the surface <NUM> by inserting guiding rods attached to the chamber top <NUM> (illustrated as guiding rods 1104a and 1104b in <FIG>) into apertures on the support structures <NUM>. The insertion of the guiding rods 1104a, 1104b into the apertures of the support structures <NUM> ensures that, as the carrier arm <NUM> is lowered, the corresponding descent of the chamber top <NUM> results in a "linear descent" as described above. A more detailed description of each of the individual components of the system <NUM> is provided below.

<FIG> illustrate a perspective view and a top view, respectively, of the chamber top <NUM> that is used with the open chamber device <NUM>. As depicted, the chamber top <NUM> includes a set of guiding rods 1104a and 1104b that are used to initially position the chamber top <NUM> onto the extension tip <NUM> of the carrier arm <NUM> and also ensure that the initial position of the chamber top <NUM> is substantially parallel to the surface <NUM>.

The chamber top <NUM> additionally includes a membrane <NUM> (illustrated in <FIG>) that includes a truncated pyramid member <NUM> extending from the bottom surface <NUM> (illustrated in <FIG>) of the chamber top <NUM>. In operation, as the chamber top <NUM> is lowered using the carrier arm <NUM>, the top surface of the truncated pyramid <NUM> faces toward the surface <NUM> as the chamber top <NUM>.

In some instances, the membrane <NUM> is a flexible membrane spread across a rigid fame. The membrane is "elastic" in a sense that it capable of deforming as a force is applied toward its surface and then has the ability to conform back to a flat surface after the applied force is removed. For example, the flexible membrane can be used to prevent the application of a rigid force on top of the sample above the surface <NUM> as the chamber top <NUM> is lowered. This ensures that the top of the truncated pyramid <NUM> pushes down on the sample due only to a gentle, predetermined force to displace the excess volume from the chamber formed between the truncated top of the pyramid <NUM> (i.e., the surface that faces the surface <NUM> of the light sensor <NUM>) and the surface <NUM> of the light sensor <NUM>.

The top surface of the truncated pyramid member <NUM> can be designed such that its surface area corresponds to the surface area <NUM>. In addition, the truncated pyramid member <NUM> is composed of a transparent material (e.g., glass, plastic, acrylic, among others) such that light <NUM> produced by the light source <NUM> can pass through the truncated pyramid member <NUM> and reach the light sensor <NUM> to collect an image of the volume of the sample <NUM> placed between the top surface of the truncated pyramid member <NUM> and the surface <NUM> of the light sensor <NUM>.

Although the truncated pyramid member <NUM> is described here to be constructed from transparent material (e.g., glass or plastic) to allow for the transmission of light into a sample and then to the light sensor <NUM>, in some implementations, the truncated pyramid member <NUM> can be constructed with an opaque material for use in dark field illumination microscopy where only light scattered by the sample is to be detected on the light sensor <NUM>. In other implementations, the top surface of the truncated pyramid member <NUM> can also be modified to be transparent only to restricted wavelengths of light with the use of a particular color pigment within the transparent material of the member or on its top or bottom surface, or with the deposition of a thin film spectral filter on the top or bottom surface.

The chamber top <NUM> may additionally include a set of weighting elements <NUM> that evenly distributes the weight along the bottom surface of the chamber top <NUM> such that the chamber top <NUM> descends substantially in parallel towards the surface <NUM> as the carrier arm <NUM> is lowered. Although figure 8B depicts an example of an arrangement of the weighting elements <NUM>, in other implementations, the weighting elements <NUM> can be positioned in other arrangements so long as the arrangement provides a means to lower the chamber top <NUM> substantially parallel to the surface <NUM>.

<FIG> illustrates an example of a top view of the open specimen chamber <NUM>. The open specimen chamber <NUM> includes a surface and chip <NUM> as described previously with respect to <FIG>.

<FIG> illustrates an example of a top view of the carrier arm <NUM>. As described here, the carrier arm <NUM> includes an extension tip <NUM> which freely supports the chamber top <NUM> in its initial placement. In operation, the actuating device <NUM> of the system <NUM> is used to manually or automatically lower the height of the carrier arm <NUM> relative to the surface <NUM> of the base of the system <NUM> (as illustrated in FIG. 8B) such that, as the height decreases, the chamber top <NUM> is lowered towards the surface <NUM> of the light sensor <NUM>.

The carrier arm <NUM> is capable of descending to a height with respect to the open specimen chamber <NUM> such that, after a certain height, e.g., at the height of the open specimen chamber <NUM> from the base of the system <NUM>, the chamber top <NUM> is no longer supported by the extension tip <NUM> of the carrier arm <NUM> because the top surface of the truncated pyramid member <NUM> is in contact with the sample <NUM> placed on top of the surface <NUM>.

Once the height of the carrier arm <NUM> from the surface <NUM> of the base is less than the height of the specimen chamber <NUM>, the chamber top <NUM> is freely settled on top of surface <NUM> rather than on the carrier arm <NUM>, which causes excess volume of the sample <NUM> placed on top of the surface <NUM> to flow out of the chamber formed by the top surface of the truncated pyramid member <NUM> and the surface <NUM>, as described previously with respect to <FIG>. In this regard, a gravitational force exerted on the chamber <NUM> can be used to form a substantially uniformly distributed volume of the sample <NUM> over the surface <NUM> without the use of an external force as described here with respect to other implementations.

<FIG> illustrate perspective views of a point-of-care blood counting device <NUM> that can be used in resource-limited regions and/or other areas without access to traditional laboratory benchtop reagents and equipment. In this implementation, the contact microcopy system is housed within a portable housing <NUM> that includes a compartment for a mobile device <NUM>, and a compartment for portable microscopy setup, as described more particularly below. In some instances, the portable microscopy setup can include a more sophisticated setup as illustrated in <FIG> that includes a latch mechanism and rotary damper to descend the chamber top <NUM>.

In general, device <NUM> is capable of capturing images of a blood sample without the need for any external equipment beyond the sample dispensing apparatus as illustrated in <FIG>. The user device <NUM> can be any type of mobile computing device that is capable of performing computing operations and capturing images. In some implementations, the user device <NUM> includes software (e.g., a mobile application) that enables a user to capture an image of a blood sample without significant training or sample preparation.

In some instances, the device <NUM> can be used in resource-limited regions in the developing world where the operator that performing a blood count test lacks the training necessary to perform a blood count using traditional microscopic techniques. In such instances, the device <NUM> can be used to provide a low ease-of-use, portable means to accurately provide a blood count with limited sample preparation and processing. For instance, the user device <NUM> can provide an interface that enables the operator to dispense a volume of the sample <NUM> into the portable microscopy setup, and then capture an image of the dispensed blood by providing a simple user input on the user device <NUM>. Particular descriptions related to the components of the portable microscopy setup are provided in greater detail below.

<FIG> illustrate various views of device <NUM> including a compartment for housing the portable microscopy setup. The setup includes a carrier arm <NUM>, a slot <NUM> to hold the chamber top, a headboard <NUM> with a sample recess <NUM>, and a sample delivery module <NUM> with pipette aperture <NUM>. The chamber top <NUM> can be attached and/or configured to the carrier arm <NUM> in a variety of configurations. In some instances, the chamber top <NUM> is a separable component that includes a truncated pyramid <NUM> depicted in <FIG>. In addition, the device <NUM> further includes a light source that is place directly above the carrier arm <NUM> (and the chamber top <NUM>) when the lid of the housing <NUM> is the closed position, and a sensor (not shown) such as the light sensor <NUM> at the bottom of the sample recess <NUM>.

In operation, the initial configuration of the carrier arm <NUM> faces upward to enable an operator to prepare the device <NUM> for an imaging operation as illustrated in <FIG>. A chamber top <NUM> is inserted into the slot <NUM> in the carrier arm <NUM> such that the top surface <NUM> of the truncated pyramid will, when the carrier arm is fully descended, face the surface <NUM> inside the sample recess <NUM>. A volume of a sample can then be introduced into the sample recess <NUM> using a pipette and inserting the tip of the pipette through the aperture <NUM> of the sample delivery module <NUM> as illustrated in <FIG>. The dimensions of the aperture <NUM> can configured for use with a specific type of pipette used, and for the volume of sample to be dispensed into the sample recess <NUM>. For instance, the aperture <NUM> can be larger for larger-sized pipettes so that when the corresponding pipette is inserted into the sample aperture <NUM>, the tip of the pipette that dispenses the volume of the sample is above the center point of the sample recess <NUM>. In some instances, the sample delivery module <NUM> may be interchangeable such that a single device <NUM> can be used with different types of pipettes.

Once the volume of the sample is dispensed into the sample recess <NUM>, the carrier arm <NUM> is then descended towards the headboard <NUM>. For instance, as the carrier arm <NUM> with the chamber top <NUM> descends towards the headboard <NUM>, coming to a stop at a position, set by the thickness of the slot feature <NUM>, where the chamber top <NUM> is resting on the spacing features <NUM>, no longer supported by the lower flanges of the slot <NUM>. In this configuration, after the carrier arm <NUM> is descended to its final position, as described above, the top surface of the truncated pyramid can then press on volume of the sample dispensed in the sample recess <NUM> such that the excess sample volume flows out of the chamber defined by the top surface of the truncated pyramid <NUM> and the surface <NUM>, as described previously, with respect to the Open Chamber Device. Once the carrier arm and the chamber top <NUM> is in this position, the lid of the housing <NUM> can then be closed to exclude extraneous light and an image of the sample can be captured using the user device <NUM> as a controller for the light sensor <NUM> beneath the sample recess <NUM>.

In some implementations, the portable microscopy setup of the device <NUM> includes an improved closure mechanism apparatus <NUM> illustrated in <FIG>. The apparatus <NUM> is similar to that of the device <NUM> depicted in <FIG>, but includes additional mechanical components (e.g., a latch mechanism <NUM> , a spring (not shown) to drive descent of the carrier arm once the latch is released, and a rotary damper <NUM> to regulate the rate of carrier arm descent) to more effectively lower a carrier arm <NUM> on to the surface <NUM> to accurately place the truncated pyramid of the chamber top <NUM> onto the surface <NUM> of the light sensor <NUM> within the sample aperture <NUM>. In this regard, the apparatus <NUM> can be implemented into the device <NUM> to improve ease-of-use (e.g., reducing the need to manually lower the carrier arm <NUM> in a specific manner) and reduce result variability between subsequent imaging procedures.

<FIG> illustrate different views of a closed chamber device <NUM> for performing complete blood counts, as described throughout this disclosure, among other types of tests. Compared to the open chamber device <NUM> described previously, the closed chamber device <NUM> reduces the need to manually load or remove a sample onto or from the surface <NUM> and encloses the sample such that the operator is not exposed to potentially harmful components of the sample. In addition, the device <NUM> enables automatic cleaning of the surface <NUM> by injecting a volume of a cleaning reagent into the closed chamber.

The closed chamber device <NUM> includes a headboard <NUM> attached to an enclosing body <NUM> with a set of rigid walls <NUM> permanently bonded to the headboard <NUM> and the enclosing body <NUM>. The enclosing body <NUM> can be any type of suitably transparent rigid material such as glass, acrylic, plastic, etc., that enables transmission of light from a light source above the enclosing body <NUM> in the enclosed space within the rigid sidewalls <NUM>, which is described more particularly below. The headboard <NUM> may be an integrated circuit board that includes a light sensitive sensor such as the light sensor <NUM> with a surface <NUM> that is exposed to a sample fluid during an imaging operation.

<FIG> illustrate a top view and cross-sectional view, respectively. Once the enclosing body headboard <NUM>, the rigid sidewalls <NUM> and the enclosing body <NUM> are permanently bonded together, an enclosed space is formed within the rigid sidewalls <NUM>. The outer portion of the enclosed space within the rigid sidewalls <NUM> includes a pressure chamber <NUM> where positive or negative pressure may be applied through the aperture <NUM> on the rigid sidewalls <NUM>. The aperture <NUM> can be placed on any of the rigid walls so long as the application of negative and positive pressure can be uniformly distributed throughout the entire volume of the pressure chamber <NUM>.

The pressure chamber <NUM> surrounds a set of deformable sidewalls <NUM> enclosing a fluid chamber <NUM>. The deformable sidewalls <NUM> can be made of any suitable solid material that withstands the applied pressure within the pressure chamber <NUM>. In some instances, the deformable sidewalls <NUM> may be made of a solid elastomer that is capable of deforming as a result of the applied pressure to the pressure chamber <NUM>. The chamber top <NUM> of the fluid chamber <NUM> is a transparent solid or rigid material that allows for the passage of light from a light source into the fluid chamber <NUM>. The chamber top <NUM> is rigid such that any pressure applied to the pressure chamber <NUM> does not cause it to deformation, preserving its smooth flat surface facing the surface <NUM> of the light sensor <NUM>. The chamber top <NUM> is affixed to the deformable side walls <NUM> to allow for varying heights of the fluid chamber <NUM> as a result of the negative or positive pressure applied to the pressure chamber <NUM>, as described more particularly below.

<FIG> illustrates an example of operating the closed chamber device <NUM> prior to performing an imaging procedure. As described previously, sample fluid to be analyzed enters the fluid chamber <NUM> through the inlet port <NUM> and exits the fluid chamber <NUM> through the outlet port <NUM>. In an initial state, the height of the fluid chamber <NUM> is increased to enable the injection of sample fluid into the fluid chamber <NUM> (e.g., shown on the left side of <FIG>). This is accomplished by generating a pressure differential between the pressure chamber <NUM> and the fluid chamber <NUM> by applying a negative pressure to the pressure chamber <NUM>. In some instances, the negative pressure may be provided by applying a suction force through the aperture <NUM> to withdraw a volume of liquid or gas contained within the pressure chamber <NUM>. The difference in pressure between the pressure chamber <NUM> and the fluid chamber <NUM> causes the deformable sidewalls <NUM> to deform to a state 1440a to accommodate the volume of sample fluid that enters into the fluid chamber <NUM>, resulting in an increase to the height of the fluid chamber <NUM>.

Claim 1:
An apparatus comprising:
a solid member (<NUM>) of transparent material;
a light sensitive imaging sensor (<NUM>);
a deformable member (<NUM>) coupling the solid member (<NUM>) to a surface (<NUM>) including the light sensitive imaging sensor (<NUM>), the deformable member comprising sidewalls (<NUM>) enclosing a fluid chamber (<NUM>) configured to receive a volume of fluid, the fluid chamber (<NUM>) comprising an inlet port (<NUM>) and an outlet port (<NUM>), the light sensitive imaging sensor (<NUM>) exposed within the fluid chamber (<NUM>), the height of the fluid chamber (<NUM>) being dependent on a position of the solid member (<NUM>) with respect to the light sensitive imaging sensor (<NUM>); and
a pressurizable chamber (<NUM>) distinct from the fluid chamber (<NUM>), enclosing a liquid or gas impinging on an exterior of the fluid chamber (<NUM>), and configured to deform the deformable member (<NUM>) to cause adjustment to a height of the fluid chamber (<NUM>), the pressurizable chamber comprising an aperture (<NUM>) through which a fluid under pressure can be applied.