Patent Description:
This invention was made with Government support under Grant No. U54 EB015403 awarded by the National Institutes of Health (NIH). The Government has certain rights in the invention.

White blood cells (WBCs, also referred to as leukocytes or leucocytes) are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. WBCs can exist not only in the blood, but also in the lymphatic system and tissues. Some conditions can trigger a response in the immune system and cause an increase in the number of WBCs (also referred to as WBC count). Other conditions can affect the production of WBCs by the bone marrow or the survival of existing WBCs in the circulation system. As these examples illustrate, various conditions can cause a change (either an increase or a decrease) of the number of circulating WBCs. Therefore, WBC count can be a relevant physiological parameter for the diagnosis, monitoring, and/or treatment of various conditions including, but not limited to, bacterial and viral infections (e.g., pneumonia or meningitis), bone marrow functionality associated with chemotherapy toxicity, and hematologic proliferative processes such as leukemia.

In current clinical practice, most of the tests to derive WBC count are performed with large-scale equipment in central clinical laboratories. Generally, these ex vivo tests are still invasive because blood samples are collected from a patient (usually a full vial of blood is needed for each test). These blood samples are then transported, queued, and analyzed in laboratory tests, thereby taking several days to receive any results. This procedure can be burdensome for patients who need regular WBC counts or for patients with emergent conditions as well as their care. In addition, due to the ex vivo nature of conventional blood tests, there can be a certain bias of some parameters owing to the inherent differences between the measurements and the true physiological properties.

Related <CIT> and <CIT> generally disclose nailfold imaging devices that include a finger well, as illustrated in <FIG>. The finger well <NUM> of the imaging device <NUM> accommodates the user's finger <NUM> in the imaging device <NUM> and contains optical immersion oil. The finger well <NUM> also includes a flat optical window <NUM>, to allow for illumination and for time-lapse microscopic imaging of the nailfold region of the user's finger <NUM> through the optical window <NUM>. In such a finger well design, the rigid housing that forms the finger well <NUM> can provide enough space to accommodate different finger sizes, but can leave a gap between the finger and the housing, allowing space for the finger to move easily. Even with the user's hand resting on the housing for stability, this can result in involuntary movement of the finger that can make video recordings and/or imaging difficult. One potential solution is to 'under-size' the finger well to reduce finger movement; however, this limits the range of finger sizes that the device can accomodate. Similar designs with same purpose are also disclosed in the following documents: "<NPL>), <CIT> and <CIT>. The articles by Bourquard Aurélien additionally disclose padding inserts for small fingers.

A finger insert for a nailfold imaging device, as defined by claim <NUM>, includes a housing an opening to receive a finger of a subject. The housing defines a landing region abuts against a distal phalange of the finger of the subject when the finger is placed into the finger insert via the opening. The housing holds a liquid to facilitate imaging of a nailfold of the finger of the subject, such that at least the distal phalange of the finger is immersed in the liquid when the liquid is present in the finger insert and as the finger is placed into the finger insert via the opening. The housing includes a first wall and a second wall, with the second wall being optically transparent to facilitate imaging of the nailfold of the finger. The finger insert further includes a deformable pad positioned on at least a portion of the first wall, to form an open-pore structure that fills a gap between the first wall and the finger of the user when the finger is inserted into the finger insert, and to reduce trapped air in the liquid when the liquid is present in the finger insert, during insertion and movement of the finger in the finger insert.

A system, that does not form part of the claimed invention, includes a finger imaging device including a light source, a detector, and a receptacle including an imaging window. The light source and the detector are optically coupled to the imaging window. The system also includes a finger insert, the finger insert being disposable in the receptacle. The finger insert includes a housing defining an opening an opening to receive a finger of a subject, and further defining a landing region that abuts against a distal phalange of the finger of the subject when the finger is placed into the finger insert via the opening, to hold a liquid to facilitate imaging of a nailfold of the finger of the subject. At least the distal phalange of the finger is immersed in the liquid when the liquid is present in the finger insert and as the finger is placed into the finger insert via the opening. The housing includes a first wall and a second wall, the second wall being optically transparent to facilitate imaging of the nailfold of the finger via the light source and detector. The finger insert further includes a deformable pad positioned on at least a portion of the first wall, to form an open-pore structure that fills a gap between the first wall and the finger of the user when the finger is inserted into the finger insert, and to reduce trapped air in the liquid when the liquid is present in the finger insert, during insertion and movement of the finger in the finger insert.

A kit, that does not form part of the claimed invention, includes a finger imaging device including a light source, a detector, and a receptacle including an imaging window. The light source and the detector are optically coupled to the imaging window. The kit also includes a set of finger inserts, each finger insert of the set of finger inserts being disposable in the receptacle such that at least a section of the second wall of that finger insert is in optical communication with the imaging window when that finger insert is disposed in the receptacle. A first finger insert of the set of finger inserts is different from a finger insert apparatus of the set of finger inserts in one or more of a length of the housing along its longitudinal axis, and an average cross-sectional area of a curved portion of the first wall.

A method, as defined by claim <NUM>, includes receiving a finger of a user in a finger insert disposed in a nailfold imaging device. The finger insert includes a housing defining an opening an opening to receive a finger of a subject, and further defining a landing region abuts against a distal phalange of the finger of the subject when the finger is placed into the finger insert via the opening, to hold a liquid to facilitate imaging of a nailfold of the finger of the subject. At least the distal phalange of the finger is immersed in the liquid when the liquid is present in the finger insert and as the finger is placed into the finger insert via the opening. The housing including a first wall and a second wall, the second wall being optically transparent to facilitate imaging of the nailfold of the finger. The finger insert also includes a deformable pad positioned on at least a portion of the first wall, to form an open-pore structure that fills a gap between the first wall and the finger of the user when the finger is inserted into the finger insert, and to reduce trapped air in the liquid when the liquid is present in the finger insert, during insertion and movement of the finger in the finger insert. The method further includes imaging a nailfold portion of the finger via the wall portion of the finger insert using the nailfold imaging device.

The invention is solely defined by the appended independent claims <NUM>,<NUM>.

The drawings are not necessarily to scale; in some instances, various aspects of the inventive subject matter disclosed herein may be shown exaggerated or enlarged in the drawings to facilitate an understanding of different features. In the drawings, like reference characters generally refer to like features (e.g., functionally similar and/or structurally similar elements).

Following below are more detailed descriptions of various concepts related to, and implementations of, kits, systems, devices, and methods that encompass finger inserts for nailfold imaging. It should be appreciated that various concepts introduced above and discussed in greater detail below may be implemented in numerous ways. Examples of specific implementations and applications are provided primarily for illustrative purposes to enable those skilled in the art to practice the implementations and alternatives apparent to those skilled in the art.

The figures and example implementations described below are not meant to limit the scope of the present implementations to a single embodiment. Other implementations are possible by way of interchange of some or all of the described or illustrated elements. Moreover, where certain elements of the disclosed example implementations may be partially or fully implemented using known components, in some instances only those portions of such known components that are necessary for an understanding of the present implementations are described, and detailed descriptions of other portions of such known components are omitted so as not to obscure the present implementations.

Generally, a finger insert as described herein can include and/or encompass a removable piece that is inserted into a nailfold imaging device before a measurement (e.g., imaging, video recording) starts, and is removed afterwards. In one aspect, the finger insert may be single-use and disposable, or reusable. In another aspect, the finger insert can be designed to engage with the nailfold imaging device ergonomically and securely, such that it provides a sturdy yet comfortable support for the finger while in use.

As described in greater detail later, the finger insert can include an incorporated optical window to ensure that the optical path between the imaging and illumination optics is clean and transparent each time. Immersion oil can be pre-filled into the finger insert to prevent reuse and contamination of immersion oils with particulates. The insert accommodates different finger sizes through variable internal geometry, with different sized inserts available (e.g., small-long, small-short, medium-long, medium-short, large-long, large-short).

In another aspect, the finger insert includes one or more flexible spacers to effectively and comfortably fill a gap that may be present between the rigid body of the finger insert and the finger of the subject. In one example discussed in further detail below, the flexible spacers may be implemented as rubber cylinders extruded from (and extending from) the walls of the body of the finger insert. In one aspect, the open-pore structure of the rubber cylinders significantly mitigates the trapping of air which would otherwise occur with semi-closed-pore structures like sponges, that would produce air bubbles in the immersion oil under the typical compression that occurs during inserting and movement of the finger.

<FIG> illustrates aspects of finger geometry that can be considered when designing inventive finger inserts according to the present disclosure to accommodate various finger sizes. As a first example aspect, cross-sectional area and shape along the length of the finger (e.g., see the cross-sectional profiles <NUM>, <NUM>, <NUM> along the length of the finger) can affect how securely the finger fits into the opening in the finger insert, and also how much force is applied on the finger. Excessive force on the finger can result in restriction of blood flow (that could in turn impede measurement made on the nailfold capillaries of that finger), and too little support or restriction would reduce the necessary constraint for minimizing involuntary movement.

A second example aspect can be the length of the finger from fingertip to nailfold (e.g., the length <NUM>), which is typically the same or similar to the fingernail length of that finger. The finger insert is designed such that the fingertip registers with the bottom of the insert, so that the distance between the end of the finger and the nailfold affects how high the nailfold sits in the well of the finger insert. This can be significant since the nailfold would need to fall within a region where the nailfold imaging device is able to image the nailfold region.

<FIG> illustrates an example finger insert <NUM>. The insert <NUM> can include a housing <NUM>, a plate <NUM> (that may or may not be integrally formed with the housing), and multiple spacers <NUM> that are deformable by a user's finger when inserted into the insert <NUM>. The housing <NUM> and the plate <NUM> can be made from a substantially rigid, inelastic material such as a transparent thermoplastic (e.g. Poly(methyl methacrylate), or PMMA). The spacers can be made from an elastic, deformable material such as a silicone. In some cases, the material of the spacers can be optically transparent, while it can be absorbing in some other cases.

The housing can include a top end <NUM> that has an opening to receive the user's finger, and a bottom end <NUM>. A body <NUM> of the housing <NUM> is disposed and/or otherwise formed between the top end <NUM> and the bottom end <NUM>, and can hold an immersion oil. The immersion oil can be selected to have a refractive index (e.g., a RI of about <NUM>) that is similar to that of the housing and/or the dermis of the finger, to facilitate the nailfold imaging. The housing <NUM> can be sized to hold enough immersion oil such that at least the distal phalange of the finger is fully immersed in it. The housing <NUM> can include a curved portion <NUM> and a wall portion <NUM>. The wall portion <NUM> can be optically transparent and substantially flat to prevent spurious reflections that can arise due to the illumination. In some cases the wall portion <NUM> can be curved, or another suitable form to conform to the nailfold imaging device during use.

The curved portion <NUM> can have a cross-sectional area (CSA) that (in at least a portion of the curved portion <NUM>) continuously or discontinuously changes from the top end <NUM> to the bottom end <NUM>. As explained above in connection with <FIG>, such a CSA profile can accommodate for the typical changes in CSA of a user's finger along its length, towards the nailfold region. The curved portion <NUM> can be optically transparent, or absorbing to prevent reflection of a light beam from the light source of the nailfold imaging device.

The CSA can vary from about <NUM><NUM> to about <NUM><NUM> from the top end <NUM> to the bottom end <NUM>. The depth of the housing from the top end <NUM> to the bottom end <NUM> can vary from about <NUM> to about <NUM>.

The plate <NUM> is disposed, attached, coupled and/or otherwise present at the bottom end <NUM> of the housing <NUM> and can abut against a distal phalange of the finger of the subject to position the finger for imaging. The plate <NUM> and the bottom end <NUM> can form a fluid-tight seal to prevent the immersion oil from leaking.

As also shown in <FIG>, multiple, deformable spacers <NUM> can be positioned, attached, formed, and/or otherwise disposed on the curved portion <NUM>. The number, size, shape, and/or other aspects of the spacers <NUM> can be useful for forming an open-pore structure that can effectively and significantly fill a gap between the curved portion <NUM> and the finger of the user when inserted. Further, the spacers <NUM> can be designed to accommodate a variety of finger geometries, with the goal of providing support to minimize unintentional movement during the measurement. Additionally, the open-pore structure of the spacers <NUM>, even when deformed due to the pressure from the user's finger, significantly reduces or eliminates trapped air in the immersion oil when the user's finger is inserted into the insert, or moved around within the insert.

<FIG> illustrates a system <NUM> that includes a finger insert <NUM>, which can be structurally and/or functionally similar to the insert <NUM>. The system also includes a nailfold imaging device <NUM>, which can be similar to such devices disclosed in the related <CIT> and <CIT>. The insert <NUM> is inserted into a receptacle <NUM> of the device <NUM> to achieve a firm mating to allow for rigid mechanical coupling of the insert <NUM> and device <NUM>, and to achieve a stable optical alignment for imaging the nailfold region of a finger in the insert <NUM>. <FIG> generally illustrates an example nailfold imaging device <NUM> (also referred to as a "WBC detection and analysis system") that includes a finger holder <NUM> with a receptacle <NUM> (also referred to as a "finger hold"). An imaging window <NUM> is formed within the receptacle <NUM> can be in optical communication with the interior of the insert <NUM> via its wall portion to permit nailfold imaging of the user's finger in the inert.

The device <NUM> can include an imager/imaging setup <NUM> that includes a light source (not shown) to illuminate the user's nailfold region within the insert <NUM> via the window <NUM>. The imager <NUM> includes a focusing optic <NUM> to collect light reflected or scattered from the finger and detector <NUM> to receive the reflected or scattered light so as to form images of the finger. The device <NUM> further includes a processor <NUM> operably coupled to the imager <NUM> and a memory <NUM> operably coupled to the processor <NUM>. The memory <NUM> is encoded with processor-executable instructions, which, when executed by processor <NUM>, may perform the methods described in the '<NUM> and/or the '<NUM> publications to analyze images received from the imager <NUM>. The device <NUM> also includes a display <NUM>, which can display the images or videos taken by the imager <NUM> and/or data associated with WBC events detected by the processor <NUM>.

<FIG> shows the insert <NUM> without the spacers and without any immersion oil, and illustrates the optical clarity of the insert <NUM>. <FIG> illustrates the insert of FIG. 3A with immersion oil added.

<FIG> illustrates another insert design, where insert <NUM> does not include the wall portion of the insert <NUM>, and wherein the plate <NUM> has a relatively more rounded profile than the plate <NUM> to better conform to a user's fingertip, and to prevent inadvertent movement. In some cases, however, the plate <NUM> can be substantially flat.

As illustrated in <FIG>, when the insert <NUM> is inserted into the nailfold imaging device <NUM> and immersion oil is added, the lack of the wall portion can provide for fewer coupling layers between the device and the user's finger, and a simplified design relative to that of the insert <NUM>. Such a setup can require removal and replacement of immersion oil within the receptacle of the device <NUM>, periodic cleaning to avoid accumulation of dirt and/or dust, and replacement of the imaging window (e.g., the window <NUM>) due to potential scratching over time, which can deteriorate imaging.

Aspects disclosed herein can also include a kit of finger inserts (e.g., the insert <NUM>, <NUM>, etc.). At least some of the inserts in the kit can be identical to each other, while in some cases, at least some of the inserts can be different in, for example, length of the housing, the cross-sectional profile of the curved portion, and so on. In this manner, the kit can include enough identical inserts for typical finger sizes and profiles, for repeated imaging thereof, and/or for varied finger sizes and profiles. In some cases, the kit can include the nailfold imaging device itself as well.

<FIG> illustrates a housing <NUM> of another finger insert design. The housing <NUM> includes an opening <NUM> through which a user can insert their finger into the housing. Upon insertion, the distal phalange of the finger of the user can land on and/or abut against a landing region <NUM> of the housing <NUM>. The landing region <NUM>, can generally form, at least in part, a curved socket that conforms to the shape of the tip of a typical human finger. The curved socket can be positioned to ensure that the user's finger lands landed approximately centered about a longitudinal axis A-A' of the housing <NUM> in the view illustrated in <FIG>.

Generally, the housing <NUM> can form a fluid-tight seal to hold a substance, e.g., an immersion oil or any other suitable liquid, to facilitate imaging. For example, the immersion oil can have a refractive index (e.g., a RI of about <NUM>) that is similar to that of the housing <NUM> and/or the dermis of the finger, to facilitate the nailfold imaging. The housing <NUM> can be sized such that at least the distal phalange of the user's finger is within the housing <NUM>, and can be immersed in the substance, to permit imaging of the nailfold region. For example, a length of the housing, such as along the axis A-A', can be from about <NUM> to about <NUM>, including all values and sub-ranges in between. The housing <NUM> can be wholly or partly formed of an inelastic material such as, for example such as an optically transparent thermoplastic (e.g. Poly(methyl methacrylate), or PMMA) glass (e.g., amorphous or crystalline), quartz (e.g., including Herkimer diamond, rock crystal, etc.), and/or the like. It is understood that imaging of the nailfold region can encompass imaging of at least some portion of the nailfold. For example, it is not required that the entire nailfold of the finger be exposed and/or otherwise available for imaging (e.g., due to the size of the imaging window of the imaging device), and imaging of the exposed portion of the nailfold can be sufficient for the purposes laid out herein, including for white blood cell measurements.

The housing <NUM> can be formed of a first wall <NUM> and a second wall <NUM>, forming a fluid-tight seal as described above. The walls <NUM> can be integrally formed, or separately formed and fused, joined, glued, and/or otherwise combined together to yield the housing <NUM>. The second wall <NUM>, which can interface with imaging components (e.g., an illumination source, a detector, and/or the like) of a nailfold imaging device during use can be substantially optically transparent in the range of about <NUM> to about <NUM>, including all values and sub-ranges in between. In some cases, the first wall <NUM>, and/or a portion thereof, can be substantially optically transparent as well. As explained in greater detail below, the walls <NUM>, <NUM> can include various portions that accommodate a user's finger, and act in concert to maintain it in place, during use. The first wall <NUM> can be curved (e.g., round, elliptical, oval, parabolic, a curved spline, and/or the like) with respect to the axis A-A', as illustrated in <FIG>. The second wall <NUM> can be flat (e.g., sheet-like) with respect to the axis A-A'.

The first wall <NUM> can define a wall portion 860a, a wall portion 860b adjacent to the wall portion 860a, and a wall portion 860c adjacent to the wall portion 860b. The second wall portion can define a wall portion 865a, a wall portion 865b adjacent to the wall portion 865a, and a wall portion 865c adjacent to the wall portion 865b. These wall portions 865a, 865b, 865c, 860a, 860b, and 860c are sometimes also referred to here as a first wall portion, a second wall portion, a third wall portion, a fourth wall portion, a fifth wall portion, and a sixth wall portion, respectively. It is understood that while described as separate portions, any adjacent walls portions (e.g., the wall portions 865a, 865b) may be integrally formed such as, for example, via injection molding. In some cases, the entire housing <NUM> can be formed as a single piece via injection molding. In some cases, adjacent wall portions may be separately formed and fused, joined, glued, and/or otherwise combined together to form their respective wall.

Referring to the second wall <NUM>, an edge/side of the wall portion 865a can form a portion of the rim of the opening <NUM>, as best illustrated in <FIG>. The wall portion 865a can be substantially optically transparent to permit imaging of the nailfold region of the user's finger. The wall portion 865a can be substantially flat in its entirety, or in part such as, for example, towards the wall portion 865b. During use a knuckle of the user's finger, e.g., the distal interphalangeal joint, can abut or lie against the wall portion 865a, as illustrated in <FIG> for the knuckle K, and described in greater detail later. The wall portion 865a can be angled with respect to, and/or form an angle with, the wall portion 865b at an angle α1, which can be about <NUM>°, about <NUM>°, about <NUM>°, about <NUM>°, about <NUM>°, including all values and sub-ranges in between. The wall portion 865c, in turn can be angled with respect to, and/or form an angle with, the wall portion 865b at an angle α2, which can be about <NUM>°, about <NUM>°, about <NUM>°, about <NUM>°, about <NUM>°, including all values and sub-ranges in between.

Referring to the first wall <NUM>, an edge/side of the wall portion 860a can form a remaining portion of the rim of the opening <NUM>, such that the wall portions 860a, 860b collective form and/or otherwise define the opening <NUM>. As illustrated in <FIG>, the opening <NUM> can be generally circular, though in other cases (not shown), the opening <NUM> can be oval, elliptical, and/or the like. Factors affecting the shape of the opening <NUM> can include, but are not limited to, ease of holding, inserting, and/or removing the housing <NUM>, ease of sealing the opening <NUM> with a fluid-tight seal, the shape of an opening of a receptacle in a finger insert device that receiving the insert <NUM>, ease of fabrication (e.g., during injection molding), and/or the like.

As described above for the first wall <NUM> and as illustrated, the wall portion 860a can be curved. The cross-sectional area defined by the wall portion 860a can be substantially the same, or continuously decrease, from the opening <NUM> towards the wall portion 860b. The cross-sectional area can be, for example, about <NUM><NUM> to about <NUM><NUM> at the opening <NUM>. In some cases, the cross-sectional area defined by the wall portion 860a can decrease in a periodic or step-wise manner, such that the wall portion 860a defines two or more different cross-sectional areas from the opening <NUM> towards the wall portion 860b. The wall portion 860a can be substantially optically transparent, e.g., similar to the wall portion 865a. In some cases, the wall portion 860a can be partially transparent, and/or composed of a light absorbing material, to prevent undesirable reflection of the excitation light during nailfold imaging. The wall portions 860b, 860c can collectively form and/or otherwise define the landing region that receives the end of the user's finger during use, as best illustrated in <FIG>, <FIG>.

<FIG> illustrates a finger insert <NUM>, which can be structurally and/or functionally similar to the finger insert <NUM>, and generally shows the insert <NUM> during use, with a finger F of a user inserted through an opening <NUM>. Unless expressly noted otherwise, similarly illustrated and labeled structures in <FIG> may be structurally and/or functionally similar to those in <FIG> such as, for example, the wall portion 965a can be similar to the wall portion 865a, and so on.

The insert <NUM> includes a pad <NUM> that is affixed, glued, and/or otherwise positioned on the first wall <NUM>, e.g., wholly, or at least partly on the wall portion 860a of the first wall. The deformable pad <NUM> includes a base layer <NUM> and multiple spacers <NUM> formed on the base layer. In some cases, the base layer <NUM> can be absent, and the spacers <NUM> can be formed directly on the first wall <NUM>. The pad <NUM> can be wholly deformable, e.g., both the base layer <NUM> and the spacers <NUM> can be composed of a deformable material such as, for example, silicone or a silicone-based material. In some cases, the base layer <NUM> and the spacers <NUM> can be composed of different materials of different deformability such as, for example, a silicone, a nitrile, a neoprene and/or other rubbers, combinations thereof, and/or the like. In other cases, the pad <NUM> can be partially deformable such as, for example, having the base layer <NUM> be composed of a rigid, inelastic material while the spacers <NUM> are composed of a deformable material.

The deformability of the spacers <NUM> can elastically deform upon insertion of the user's finger F, to press the finger F against the second wall <NUM>. Each spacer <NUM> can be suitably shaped, sized, and laid out in an open-pore structure to maintain separation between adjacent spacers in the absence of deformation. Further, the open-pore structure of the spacers <NUM> can reduce the formation of air bubbles and/or generally reduce/eliminate any trapped air in the immersion liquid that may have entered the insert <NUM> during insertion or movement of the user's finger. Such trapped air can interfere with nailfold imaging and lead to artifacts.

The spacer <NUM> can be generally columnar or cylindrical in form, including forms such as, for example, right circular cylinders, oblique cylinders, cones, oblique cones, frustums (e.g., pyramidal, or conical), prismatic (e.g., elongated prisms, truncated elongated prisms, fin-like), and/or combinations thereof. As illustrated in <FIG>, in some cases the spacers <NUM> can be substantially frustoconical in form, having a larger cross-sectional radius towards the base layer <NUM>/the wall portion <NUM>. The number of spacers can be <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or more than <NUM>, including all values and sub-ranges in between.

<FIG> also illustrates how the wall portions 960c, 965c cooperate to define and/or enclose a nail space <NUM> that can accommodate a nail N of the finger F. In this manner, the insert <NUM> can accommodate, i.e., receive in a secure fit manner, fingers of users with longer nails that extend beyond the distal end (i.e., the fingertip, also sometimes referred to as the distal phalange) of the user's finger.

Upon insertion of the finger F into the insert <NUM>, the distal end DP of the finger lands and rests on the landing region <NUM>, and is pushed against the wall <NUM> by the pad <NUM>. By virtue of the angle α1 formed between the wall portions 965a, 965b, the knuckle/joint K of the finger lands on the wall portion 965a, while the nail N of the finger lands on the region 965b, resulting in a reduction of elimination of any interaction or contact between the wall portion 965a and the nailfold region NF of the finger F. This ensures that there is little, or no pressure applied on the region NF by the wall portion 965a, permitting blood to flow through the capillaries in the region NF, and in turn permitting imaging of the capillaries. In the absence of such angling between the wall portions 965a, 965b, the region NF would be compressed against the wall, resulting in blockage of flow in the capillaries of the region NF, and impeding nailfold imaging.

Referring now to the angle α2 formed between the wall portions 965b, 965c, allowing an angle of <NUM>° -<NUM>° provides space for the lower extremity of the nail to protrude into nail space <NUM>.

<FIG>, <FIG> show a fabricated, example finger insert <NUM> (e.g., structurally and/or functionally similar to the inserts <NUM>, <NUM>) with a deformable pad that includes both a base layer <NUM> and spacers <NUM> formed on the base layer. The base layer <NUM> and the spacers <NUM> here are integrally formed, of the same deformable material. The spacers <NUM> are substantially conical in form. The finger insert <NUM> is wholly transparent in this example, and the wall portion 1060a is substantially frustoconical, i.e., it has a decreasing cross-section area from the opening inwards.

<FIG> show various views of finger inserts (e.g., structurally and/or functionally similar to any of the inserts described herein) having immersion oil disposed therein, and a fluid-tight seal at the opening. The labeling, shown in <FIG>, can indicate unit numbers and/or a scale associated with, for example, variation in geometry of the structures of the finger insert and/or the pad, volume and/or nature of the liquid contained within, and/or the like.

<FIG> shows a finger insert <NUM> (e.g., structurally and/or functionally similar to the inserts described herein) during use with a nailfold imaging device <NUM>, and with a user's finger inserted therein. A receptacle <NUM> of the device <NUM> can receive the insert <NUM> in a mating-fit manner. The device <NUM> can be configured to perform nailfold imaging of the user's finger as generally described in the '<NUM>, '<NUM> publications.

Aspects disclosed herein can be directed to kit that include multiple finger inserts (e.g., such as any finger insert described here). The finger inserts of the kit can be different from one other in any matter such as, but not limited to, a length of the housing along its longitudinal axis (e.g., along the axis A-A'), an average cross-sectional area of a curved wall portion (e.g., the wall portion 860a), variations in the geometry and/or mechanical properties of the pad (e.g., the pad <NUM>). In some cases, each finger insert can have the liquid (e.g., a sterile immersion oil) already included therein, and a leak-proof covering over its opening, similar to shown in <FIG>. In some cases, the kit can include the nailfold imaging device itself, such as the device <NUM>, the device <NUM> in <FIG>, and/or as generally described in the `<NUM>, '<NUM> publications. Such an imaging device, similar to that illustrated in <FIG> for example can include a light source to illuminate the nailfold region through the second wall (e.g., the wall <NUM>), and a detector to receive the optical signal/beam from the nailfold region. The imaging device can also include a receptacle (e.g., the receptacle <NUM>) sized and shaped to receive the finger inserts in any suitable mating manner. In some cases, a system can include one or more finger inserts, and a nailfold imaging device as described herein.

<FIG> illustrates a method <NUM>, such as for nailfold imaging. The method <NUM> includes, at <NUM>, receiving a finger of a user in a finger insert (e.g., structurally and the insert <NUM>, <NUM>, <NUM>, and/or <NUM>) disposed in a nailfold imaging device (e.g., the device of <FIG>, <FIG>, and/or as generally described in the '<NUM>, '<NUM> publications). The finger insert can include a housing (e.g., the housing <NUM>) that defines an opening (e.g., the opening <NUM>) to receive a finger of a subject, and further defining a landing region (e.g., the region <NUM>) that abuts against a distal phalange of the finger of the subject when the finger is placed into the finger insert via the opening. The housing can hold a liquid (e.g., an immersion oil) to facilitate imaging of a nailfold of the finger of the subject. In some cases, the method <NUM> can encompass adding the liquid to the finger insert prior to step <NUM>.

At least the distal phalange of the finger is immersed in the liquid when the liquid is present in the finger insert and as the finger is placed into the finger insert via the opening. The housing including a first wall (e.g., the wall <NUM>) and a second wall (e.g., the wall <NUM>), the second wall being optically transparent to facilitate imaging of the nailfold of the finger. The method <NUM> can also include inserting the finger insert into a receptacle of the nailfold imaging device. The nailfold imaging device includes a light source and a detector, and the receptacle includes an imaging window such that the light source and the detector are optically coupled to the imaging window.

The method also includes, at step <NUM>, imaging a nailfold portion of the finger via the wall portion of the finger insert using the nailfold imaging device. The imaging can include includes imaging the portion of the finger with the light source and detector via the imaging window and via the second wall of the finger insert.

It is understood that while described for imaging of nailfold regions in fingers of a user, aspects disclosed herein can be useful for imaging other portions of the body such as, for example, toes of the feet. As a non-limiting example, an insert for imaging a human toe can be shaped and sized according to the considerations laid out herein, and accounting for the specific anatomy of the human toe. One such consideration could be, for example, that toes of the human feet do not splay out to the same extent that fingers do, so a toe insert will likely have to be sized to prevent excessive and painful separation between the user's toes. Another consideration can be, for example, that toes display wider variability in size than fingers, so a toe insert may need to be designed specifically for one or fewer than all toes of a user's foot.

It is also understood that while described with respect to nailfold imaging, aspects disclosed herein can be useful for imaging other regions of a user's fingers outside the nailfold region (e.g., anywhere on the middle phalanx of the user's finger), other regions of a user's toes outside the nailfold region (e.g., anywhere on the middle phalanx of the user's finger or user's toe), and/or the like.

Patient's fingers can be used to perform a number of different physiological and healthcare tests, including, for example, the noninvasive measurement of a patient's white blood cell or neutrophil levels. These measurements often require or depend on stabilizing the finger for a certain period of time, and keeping it repeatedly within a predefined Region of Interest (ROI) in order to successfully carry out the measurement. Demonstrated here is how a custom, disposable "finger insert" can meet these needs. A series of studies were on a sample size of nine naive subjects to estimate the critical target ROI for such blood measurements, as well as the intra-subject and inter-subject variability in finger positioning within that ROI. The focus was on tracking one particular finger anatomical location, the nailfold, and it was confirmed that the finger insert disposable can repeatedly position within a <NUM> by <NUM> ROI for <NUM>% of the users. These studies demonstrate that the finger insert disposable can successfully centralize the nailfold within this defined ROI, therefore allowing its imaging through an optical system designed to cover such Field Of View (FOV). Analysis of the presented data additionally shows the capacity to collect data in a range of finger locations beyond the nailfold.

The purpose of this study was to prove that an optical system with a FOV of <NUM> by <NUM> can consistently image the nailfold region (<FIG>) of a set of naive users, across a variety of finger sizes, by employing a finger insert disposable as shown and described in <FIG>, <FIG>. To do this, the focus was on the variability of the nailfold geometries across a range of different subjects. Typically, the ring finger of the user's non-dominant hand is measured, both in conventional video capillaroscopy, which is employed for a wide range of clinical applications, as well as in other recent techniques to noninvasively measure white blood cells. However, this study incorporates multiple fingers from each subject to replicate the geometric variability between fingers of a larger sample size. The goal was to prove successful imaging of nailfold ROIs across this larger sample size. Among the criteria for success was that naive users would be able to use the finger insert intuitively, that the finger can be placed comfortably into the finger insert, and that the nailfold should fall within the correct target zone or ROI for every measurement. To this end, the finger insert should guide the user's finger to the bottom extrusion within the finger insert as well as centering the finger and making the user comfortable. The knuckle of each finger measured should have minor contact with the inside face of the finger insert to stabilize the finger and avoid excessive pressure surrounding the nailfold, which could hinder blood flow and limit the ability to collect physiological and healthcare measurements from it. The ROI center should remain still to capture the measurement, so a padding in the finger insert was designed (the base layer <NUM> and the spacers <NUM> illustrated in <FIG>, <FIG>) to secure the finger in place during the measurement with minimal vibration relative to the imaging system. The employed imaging system yields a <NUM> by <NUM> FOV, so the center of the ROI should be captured in this FOV.

The criteria of a successful measurement considered here are:.

This study was conducted to calculate each user's average nailfold ROI based on the sample of subjects. These subjects range in gender and age from <NUM> to <NUM> years old. The subjects' index, middle, and ring finger were studied five times each in every test as a means to examine more finger size and geometry varieties. The finger insert and camera were kept in a constant location throughout every picture. Using a marker, a trained operator manually placed a dot just above the users' nailfolds to identify the nailfold ROI center where the measurement occurs (<FIG>). From these dot locations, the nailfold height and width were measured. Using ImageJ software, these ROI center locations were overlaid onto each other and graphed to better understand the range of finger sizes produced by the data (<FIG>). The finger insert of <FIG>, <FIG> was tested across nine subjects.

Each dot on <FIG> represents one data point from one finger of each subject where the ROI center falls. The maximum range of data falls between about <NUM> in the vertical direction and roughly <NUM> in the horizontal direction across all subjects.

The data indicates that the finger insert condenses the nailfold ROI centers of the sample size to a range where one can take measurements with confidence. Based on measuring the center of the nailfold, it was found that each finger has roughly a <NUM> by <NUM> span for repeatability on the same location, as discernable from <FIG>, <FIG>. By taking the center of the nailfold and measuring outwards until the end of the nailfold (<FIG>), the study found that the average width of nailfolds is <NUM> among the subjects. There is a minimal amount of translation in the vertical direction due to the geometry of the common nailfold.

In conclusion, variability was present within the test, but the data condenses to approximately <NUM> by <NUM> (<FIG>, <FIG>). Intra-subject data shows about a <NUM>-<NUM> variation in the Y-direction across the index, middle, and ring fingers (<FIG>). The most dispersed data corresponded to the left middle finger of one particular subject, and all data points fall within <NUM> by <NUM> FoV. The largest ROI encompassing all finger positions from our data was about <NUM> by <NUM>, and the largest FoV where one could image the nailfold area was <NUM> by <NUM> (<FIG>). By using pre-calibration, that is, by adjusting the Y position of the finger disposable beforehand to compensate for each user's finger length, we can image most nailfold areas within an <NUM> by <NUM> FoV.

The acts performed as part of the method may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.

Claim 1:
A finger insert (<NUM>) designed to engage with nailfold imaging device, the finger insert comprising:
a housing (<NUM>) defining an opening (<NUM>) configured to receive a finger of a subject, and further defining a landing region configured to abut against a distal phalange of the finger of the subject when the finger is placed into the finger insert via the opening, wherein the housing forms a fluid-tight seal configured to hold a liquid selected to facilitate imaging of a nailfold of the finger of the subject, wherein at least the distal phalange of the finger is immersed in the liquid when the liquid is present in the finger insert and as the finger is placed into the finger insert via the opening, the housing including a first wall and a second wall (<NUM>, <NUM>), the second wall being optically transparent to facilitate imaging of the nailfold of the finger; and
a deformable pad (<NUM>) positioned on at least a portion of the first wall, configured to form an open-pore structure, the structure being configured to fill a gap between the first wall and the finger of the subject when the finger is inserted into the finger insert, and the deformable pad being configured to reduce trapped air in the liquid when the liquid is present in the finger insert, during insertion and movement of the finger in the finger insert,
wherein the finger insert is designed to be insertable into and removable from a receptacle of the nailfold imaging device (<NUM>).