SURFACE IMAGING OF BIOLOGICAL TISSUE SAMPLES

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent Application No. 62/370,195, filed August 2, 2016, the contents of which are hereby incorporated by reference in their entirety.

GOVERNMENT RIGHTS

This invention was made with government support under grant number 1 R21 CA186791-01 awarded by the National Institutes of Health. The government has certain rights in the invention.

BACKGROUND

Unless otherwise indicated herein, the materials described in this section are not prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.

To determine a diagnosis for various diseases, such as breast cancer, pathologists typically obtain biopsies from patients. Generally, three types of biopsy procedures are used: fine needle aspiration biopsy (FNA or FNAB), core needle biopsy (CNB), and surgical (open) biopsy. Needle biopsies are the standard of care for diagnosing breast cancer as surgical biopsies are considered more invasive with no added diagnostic value. Among all needle biopsies, CNBs have been reported to have the highest accuracy for palpable breast lesion and for impalpable breast lesion due to its relative high specificity and sensitivity. But CNBs still have some drawbacks. Inadequate CNB specimens may occur due to sampling errors or distortion caused by operational errors, even though different imaging modalities, including computed tomography (CT) and ultrasonic imaging are used to provide guidance to CNBs acquisition for impalpable breast lesion. To reduce the probability of getting inadequate biopsies, instead of taking a single biopsy at one time, an average of two to five extra specimens are collected for the histology assessment. However, this extra CNBs acquisition procedure still cannot identify non-diagnostic specimens and a full histology evaluation still needs to perform on all acquired specimens, which create problems of added pain for the patient, unnecessary efforts from clinicians, and added cost of the processing of redundant biopsy specimens.

SUMMARY

Example devices and methods described herein describe various fluidic devices and methods of use. In one aspect, a fluidic device is provided including (a) a first channel having a first end and a second end, wherein the first channel is configured to receive a biological tissue sample, and (b) a second channel having a first end and a second end, wherein the second channel is in fluid communication with the first channel via an opening such that, when in use, flow in the second channel will create a rotational flow in the first channel.

In a second aspect, a system is provided. The system may include (a) the fluidic device of the first aspect, (b) an imaging device positioned adjacent to the opening fluidically connecting the first channel and the second channel, (c) at least one processor, and (d) data storage including program instructions stored thereon that when executed by the at least one processor, cause the fluidic device to perform functions. The functions may include (i) positioning a biological tissue sample in the first channel adjacent the opening fluidically connecting the first channel and the second channel, and (ii) providing a first fluid to the second channel to tangentially contact the biological tissue sample to thereby rotate the biological tissue sample in the first channel.

In a third aspect, a method is provided. The method may include (a) positioning a biological tissue sample in the first channel of the fluidic device of the first aspect adjacent the opening fluidically connecting the first channel and the second channel, and (b) providing a first fluid to the second channel to tangentially contact the biological tissue sample to thereby rotate the biological tissue sample in the first channel.

These as well as other aspects, advantages, and alternatives, will become apparent to those of ordinary skill in the art by reading the following detailed description, with reference where appropriate to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS FIGURE 1 illustrates a simplified block diagram of a fluidic device, according to an example embodiment.

FIGURE 2A illustrates a cross-section view of a circular channel of a fluidic device, according to an example embodiment.

FIGURE 2B illustrates a cross-section view of an oval channel of a fluidic device, according to an example embodiment. FIGURE 2C illustrates a cross-section view of a square channel of a fluidic device, according to an example embodiment.

FIGURE 2D illustrates a cross-section view of a rectangular channel of a fluidic device, according to an example embodiment.

FIGURE 3A illustrates a perspective view of a fluidic device, according to an example embodiment.

FIGURE 3B illustrates a side cross-section view of a fluidic device, according to an example embodiment.

FIGURE 3C illustrates a side cross-section view of a fluidic device, according to an example embodiment.

FIGURE 3D illustrates a perspective view of a fluidic device, according to an example embodiment.

FIGURE 3E illustrates a side cross-section view of a fluidic device, according to an example embodiment.

FIGURE 3F illustrates a perspective view of a fluidic device, according to an example embodiment.

FIGURE 3G illustrates a side cross-section view of a fluidic device, according to an example embodiment.

FIGURE 3H illustrates a side cross-section view of a fluidic device, according to an example embodiment.

FIGURE 4 illustrates an example system, according to an example embodiment.

FIGURE 5 is a flowchart illustrating an example method according to an example embodiment. FIGURE 6 illustrates a schematic drawing of a computer network infrastructure, according to an example embodiment.

DETAILED DESCRIPTION

Example methods and systems are described herein. It should be understood that the words " ^" example," "exemplary," and " ^" illustrative" are used herein to mean "serving as an example, instance, or illustration." Any embodiment or feature described herein as being an "example," being "exemplary," or being "illustrative" is not necessarily to be construed as preferred or advantageous over other embodiments or features. The example embodiments described herein are not meant to be limiting. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein. Furthermore, the particular arrangements shown in the Figures should not be viewed as limiting. It should be understood that other embodiments may include more or less of each element shown in a given Figure. Further, some of the illustrated elements may be combined or omitted. Yet further, an example embodiment may include elements that are not illustrated in the Figures.

In Figure 1, referred to above, solid lines, if any, connecting various elements and/or components may represent mechanical electrical, fluid, optical, electromagnetic and other couplings and/or combinations thereof. As used herein, "coupled" means associated directly as well as indirectly. For example, a member A may be directly associated with a member B, or may be indirectly associated therewith, e.g., via another member C. It will be understood that not all relationships among the various disclosed elements are necessarily represented. Accordingly, couplings other than those depicted in the block diagrams may also exist. Dashed lines, if any, connecting blocks designating the various elements and/or components represent couplings similar in function and purpose to those represented by solid lines; however, couplings represented by the dashed lines may either be selectively provided or may relate to alternative examples of the present disclosure. Likewise, elements and/or components, if any, represented with dashed lines, indicate alternative examples of the present disclosure. One or more elements shown in solid and/or dashed lines may be omitted from a particular example without departing from the scope of the present disclosure. Environmental elements, if any, are represented with dotted lines. Virtual (imaginary) elements may also be shown for clarity. Those skilled in the art will appreciate that some of the features illustrated in Figure 1 may be combined in various ways without the need to include other features described in Figure 1, other drawing figures, and/or the accompanying disclosure, even though such combination or combinations are not explicitly illustrated herein. Similarly, additional features not limited to the examples presented, may be combined with some or all of the features shown and described herein.

In Figure 5, referred to above, the blocks may represent operations and/or portions thereof and lines connecting the various blocks do not imply any particular order or dependency of the operations or portions thereof. It will be understood that not all dependencies among the various disclosed operations are necessarily represented. Figure 5 and the accompanying disclosure describing the operations of the method(s) set forth herein should not be interpreted as necessarily determining a sequence in which the operations are to be performed. Rather, although one illustrative order is indicated, it is to be understood that the sequence of the operations may be modified when appropriate. Accordingly, certain operations may be performed in a different order or simultaneously. Additionally, those skilled in the art will appreciate that not all operations described need be performed.

Unless otherwise indicated, the terms "first," "second," etc. are used herein merely as labels, and are not intended to impose ordinal, positional, or hierarchical requirements on the items to which these terms refer. Moreover, reference to, e.g., a "second" item does not require or preclude the existence of, e.g., a "first" or lower-numbered item, and/or, e.g., a "third" or higher-numbered item.

Reference herein to "one embodiment" or "one example" means that one or more feature, structure, or characteristic described in connection with the example is included in at least one implementation. The phrases "one embodiment" or "one example" in various places in the specification may or may not be referring to the same example.

As used herein, a system, apparatus, device, structure, article, element, component, or hardware "configured to" perform a specified function is indeed capable of performing the specified function without any alteration, rather than merely having potential to perform the specified function after further modification. In other words, the system, apparatus, structure, article, element, component, or hardware "configured to" perform a specified function is specifically selected, created, implemented, utilized, programmed, and/or designed for the purpose of performing the specified function. As used herein, "configured to" denotes existing characteristics of a system, apparatus, structure, article, element, component, or hardware which enable the system, apparatus, structiue, article, element, component, or hardware to perform the specified function without further modification. For purposes of this disclosure, a system, apparatus, structure, article, element, component, or hardware described as being "configured to" perform a particular function may additionally or alternatively be described as being "adapted to" and or as being "operative to" perform that function.

As used herein, with respect to measurements, "about" means +/- 5%.

As used herein, with respect to measurements, "substantially" means +/- 5%.

As used herein, two axes are "substantially perpendicular" when there is a ninety degree angle between them +/- 5%.

As used herein, "cross-sectional height" means a maximum vertical distance of a cross-section of a channel.

As used herein, "cross-sectional width" means a maximum horizontal distance of a cross-section of a channel. As used herein, "biological tissue sample" means a sample taken from a biological tissue. The sample of biological tissue may constitute a biopsy, which can be a fine needle aspiration biopsy (FNA or FNAB), a core needle biopsy (CNB), or a surgical (open) biopsy.

With reference to the Figures, Figure 1 illustrates an example fluidic device 100. The fluidic device 100 may include a first channel 102 having a first end 104 and a second end 106. The first channel 102 is configured to receive a biological tissue sample. The fluidic device 100 may also include a second channel 108 having a first end 110 and a second end 112. The second channel 108 is in fluid communication with the first channel 102 via an opening 114 such that, when in use, flow in the second channel 108 will create a rotational flow in the first channel 102. The second channel 108 is a cross-channel, cross-flow channel, or transverse channel. As such, flow in the second channel 108 is transverse to flow in the first channel 102, thereby imparting a shear stress on any object positioned in the first channel 102 adjacent to the opening 114. The first channel may a length ranging between about 1 cm and about 10 cm, and the second channel may have a length ranging between about 0.1 cm and about 5 cm.

In one particular example, the first end 104 of the first channel 102 is positioned at a first side 1 16 of the fluidic device 100, and the second end 106 of the first channel 102 is positioned at a second side 1 18 of the fluidic device 100. In such an example, the opening 1 14 fluidically connecting the first channel 102 and the second channel 108 is positioned between the first end 110 of the second channel 108 and the second end 1 12 of the second channel 102. In another example, the first end 1 10 of the second channel 108 is positioned at a third side 120 of the fluidic device 100, and the second end 112 of the second channel 108 is positioned at a fourth side 122 of the fluidic device 100. In one example, the second channel 108 is positioned substantially perpendicular to the first channel 102. In another example, the second channel 108 may be positioned diagonally with respect to the first channel 102.

The fluidic device 100 may further include a first reservoir 124 in fluid communication with the first channel 102. In one example, the first reservoir 124 is further in fluid communication with the second channel 108. In another example, the fluidic device 100 further includes a second reservoir 126 in fluid communication with the second channel 108. As such, the fluidic device 100 may include one or more pumps 128 in fluid communication with one or more of the first reservoir 124 and the second reserv oir 126.

The first end 104 of the first channel 102 may include an input interface 130 and the second end 106 of the first channel 102 may include an output interface 132. The input interface 130 and the output interface 132 may provide a fluid-tight connection mechanism to couple the fluidic device 100 to other components. For example, the input interface 130 may be configured to couple the first channel 102 of the fluidic device 100 to a coring needle such that the fluidic device 100 can received a biological tissue sample from the coring needle. The output interface 132 may be configured to couple the first channel 102 to an imaging system for further evaluation of the biological tissue sample.

The first channel 102 and the second channel 108 may take a variety of forms. For example, a cross-section of the first channel 102 and/or the second channel 108 may be circular, oval, square, or rectangular, as shown in Figures 2A-2D, respectively. The cross- sections shown in Figures 2A-2D are a vertical cross-section taken perpendicular to a direction of flow in the first channel 102 and the second channel 108. Each cross-section may have a cross-sectional height H and a cross-sectional width W, as shown in Figures 2A- 2D. A cross-sectional height H of the first channel 102 may be greater than a cross-sectional height H of the second channel 108. In particular, the cross-sectional height H of a given first channel 102 may range from about 0.2 mm to about 5 mm, and the cross-sectional height of a given second channel may range from about 0.2 mm to about 1 mm. In one example, the cross-sectional height H of the first channel and the cross-sectional height of the second channel 108 is constant along their lengths. In another example, as discussed in additional detail below, the cross-sectional height H of the first channel 102 and/or the cross-sectional height H of the second channel 108 may vary along their length. The oval cross-section may be arranged so that the cross-sectional width W is greater than the cross-sectional height H, as shown in Figure 2B. In another arrangement, the oval cross-section may be arranged so that the cross-sectional width W is less than the cross-sectional height H. Similarly, the rectangular cross-section may be arranged so that the cross-sectional width W is greater than the cross-sectional height H, as shown in Figure 2D. In another arrangement, the rectangular cross-section may be arranged so that the cross-sectional width W is less than the cross- sectional height H.

Figures 3A-3H illustrate various example fluidic devices 100, according to example embodiments. In particular, Figure 3A illustrates a perspective view of an example fluidic device 100. In such an example, the first end 104 of the first channel 102 is positioned at a first side 1 16 of the fluidic device 100, and the second end 106 of the first channel 102 is positioned at a second side 118 of the fluidic device 100. Further, as shown in Figure 3 A, the first end 110 of the second channel 108 is positioned at a third side 120 of the fluidic device 100, and the second end 112 of the second channel 108 is positioned at a fourth side 122 of the fluidic device 100. In one example, the second channel 108 is positioned substantially perpendicular to the first channel 102. As shown in Figure 3A, the opening 114 fluidically connecting the first channel 102 and the second channel 108 is positioned between the first end 1 10 of the second channel 108 and the second end 1 12 of the second channel 108. As shown in Figure 3A, the second channel 108 may be positioned above the first channel 102. In another embodiment, the second channel 108 may be positioned below the first channel 102.

In one particular example, as shown in the side cross-section view of Figure 3B, the second channel 108 is positioned tangential to the first channel 102 such that the opening 114 fluidically connecting the first channel 102 and the second channel 108 has a cross-sectional width W2 that is less than a cross-sectional width Wl of the first channel 102. This more compact second channel 108 may be duplicated with multiple parallel channels to cover a sample with larger axial extent (length) in the first channel 102. In another example, as shown in the side cross-section view of Figure 3C, the second channel 108 is positioned tangential to the first channel 102 such that the opening 1 14 fluidically connecting the first channel 102 and the second channel 108 has a cross-sectional width W2 that is greater than a cross-sectional width Wl of the first channel 102. Such an arrangement may provide increased single-channel contact area for imposing shear stress to rotate a biological tissue sample positioned in the first channel 102. The choice of size, geometry, and number of channels may depend on the type of tissue sample, moving fluid, and manufacturing method, such as three dimensional casting, molding, cutting, or printing.

Figure 3D illustrates a perspective view of another example fluidic device 100, and Figure 3E illustrates a side cross-section view of the fluidic device 100 of Figure 3D. As shown in Figures 3D and 3E, the opening 114 fluidically connecting the first channel 102 and the second channel 108 is positioned at the second end 112 of the second channel 108 such that the opening 1 14 is in fluid communication with a top portion 134 of the first channel 102. In such an example, the fluidic device 100 may further include a third channel 136 having a first end 138 and a second end 140. The first end 138 of the third channel 136 includes a second opening 142 in fluid communication with a bottom portion 144 of the first channel 102. Similar to the second channel 108, the third channel 136 is a cross-channel, cross-flow channel, or transverse channel. As such, flow in the third channel 136 is transverse to flow in the first channel 102, thereby imparting a shear stress on any object positioned in the first channel 102 adjacent to the openings 114, 142. In such an example, the first end 110 of the second channel 108 is positioned at a third side 120 of the fluidic device 100, and the second end 140 of the third channel 136 is positioned at a fourth side 122 of the fluidic device 100. In one example, a flow direction in the second channel 108 is configured to be the same as a flow direction in the third channel 136. In another example, a flow direction in the second channel 108 is configured to be in an opposite direction of a flow direction in the third channel 136.

Figure 3F illustrates a perspective view of another example fluidic device 100. As shown in Figure 3F, the fluidic device 100 includes a third channel 136 having a first end 138 and a second end 140. The third channel 136 is in fluid communication with the first channel 102 via a second opening 142. As shown in Figure 3F, the first end of 1 10 the second channel 108 and the first end 138 of the third channel 136 may be positioned at the third side 120 of the fluidic device 100, the second end 1 12 of the second channel 108 and the second end 140 of the third channel 136 may be positioned at a fourth side 122 of the fluidic device 100, and the third channel 136 may be positioned substantially perpendicular to the first channel 102. In one example, as shown in Figures 3F-3H, the second channel 108 and the third channel 136 are positioned on the same side of the first channel 102, and a flow direction in the second channel 108 is configured to be the same as a flow direction in the third channel 136. In another example, the second channel 108 is positioned on a first side of the first channel 102, the third channel 136 is positioned on a second side of the first channel 102 opposing the first side, and a flow direction in the second channel 108 is configured to be in an opposite direction of a flow direction in the third channel 136. Such an arrangement may provide increased rotational force in the first channel 102.

In one example, as shown in the side cross-section view of Figures 3G and 3H, the second channel 108 and the third channel 136 may be positioned so a cross-sectional width W2, W3 of each of the second channel 108 and the third channel 136 is tangential to a longitudinal axis of the first channel. As shown in the example shown in Figure 3G, the opening 114 fluidically connecting the first channel 102 and the second channel 108 has a cross-sectional width W2 that is less than a cross-sectional width Wl of the first channel 102, and the second opening 142 fluidically connecting the first channel 102 and the third channel 136 has a cross-sectional width W3 that is less than a cross-sectional width Wl of the first channel 102. In another example, as shown in the side cross-section view of Figure 3H, the opening 1 14 fluidically connecting the first channel 102 and the second channel 108 has a cross-sectional width W2 that is greater than a cross-sectional width Wl of the first channel 102, and the second opening 142 fluidically connecting the first channel 102 and the third channel 136 has a cross-sectional width W3 that is greater than a cross-sectional width Wl of the first channel 102. Such an arrangement may provide increased contact area for imposing shear stress to rotate a biological tissue sample positioned in the first channel 102.

In certain embodiments, such as shown in any one of Figures I-3H, example fluidic devices may be made using an additive-manufacturing process, such as stereolithography or more traditional methods of molding or casting. As such, the example fluidic devices described above may include a variety of materials, including poly(dimethylsiloxane) (PDMS) which can be optically clear in thin thicknesses from 250 nm (ultra violet) to 1600 nm (infrared) wavelength rage, as examples. In one example, the additive-manufacturing process is a multi-material additive-manufacturing process such that various components of the fluidic device 100 may be formed using a material with a greater elasticity than the other components. For example, the channels 102, 104, 106 may be created with a material having greater elasticity than the other components of the fluidic device 108, 110, 112, 138, 140. Other examples are possible as well.

Each of the fluidic devices 100 described in Figures 1-3H may represent a module, a segment, or a portion of program code, which includes one or more instructions executable by a processor or computing device for creating such devices using an additive- manufacturing system. The program code may be stored on any type of computer readable medium, for example, such as a storage device including a disk or hard drive. The computer readable medium may include non-transitory computer readable medium, for example, such as computer-readable media that stores data for short periods of time like register memory, processor cache and Random Access Memory (RAM). The computer readable medium may also include non- transitory media, such as secondary or persistent long term storage, like read only memory (ROM), optical or magnetic disks, compact-disc read only memory (CD- ROM), for example. The computer readable media may also be any other volatile or non- volatile storage systems. The computer readable medium may be considered a computer readable storage medium, for example, or a tangible storage device.

In another embodiment, the fluidic devices 100 described in Figures 1-3H may further include variations in cross-section. In such examples, the channels 102, 108, 136 may include at least a first segment and a second segment, where the first segment has a diameter that is different than that of the second segment. For example the first channel 102 opening may be larger on the first side 104 to accommodate the needle biopsy device and be nonuniform in cross section to allow for the tissue sample to be positioned within the first channel 102. The first segment can be of any suitable length, variability, etc. Further, each of the channels 102, 108, 136 may include more than two segments, such as three, four, or five segments with multiple regions of variability. Such cross-sectional area constrictions promote the abihty to measure mechanical properties of the specimen and evaluation of tissue health, i.e. viscoelasticity, stiffness, connectivity, elasticity and evaluation of the structural architecture of the extracellular matrix (and integrity) of the biological tissue sample. Such variable diameters may function as valves with no significant moving parts that aid fluid flow with respect to tissue processing, staining and transport. Variable diameters may also function as regions of direct physical interrogation, such as manual manipulation for transport, manual staining, or tissue separation (in cases where samples were improperly procured by the clinical coring needle ).

Figure 4 illustrates an example system 400, according to an example embodiment. As shown in Figure 4, the system 400 may include the fluidic device 100 as described in Figures 1-3H, an imaging device 402 positioned adjacent to the opening 114 fluidically connecting the first channel 102 and the second channel 108 of the fluidic device 100, at least one processor 404, and data storage 406 including program instructions 408 stored thereon that when executed by the at least one processor 404, cause the system 400 to perform functions. In one example, the functions include position a biological tissue sample in the first channel 102 adjacent to the opening 114 fluidically connecting the first channel 102 and the second channel 108, and provide a first fluid 102 to the second channel 108 to tangentially contact the biological tissue sample to thereby rotate the biological tissue sample in the first channel 102.

The imaging device 402 may take many forms, including but not limited to, a smartphone camera, an all-purpose digital camera, a machine vision camera (e.g., a CCD, or CMOS sensor with an attached variable or fixed focus lens), or a standalone optoelectric component, such as an LED transmitter and a photodiode, a phototransistor, or a photoresistor detector (e.g., transmitter-detector couples). Such an imaging device 402 may be configured to measure various properties of the tissue sample, for example reflectance, fluorescence, absorbance or transparency of the biological tissue sample. The imaging system 402 may further include a light source 410, such as a deep ultra-violet (UV) light source as an example and measure excited fluorescence from one or more optical stains. Other light sources of longer wavelengths 410 are possible as well.

In another embodiment, the system 400 may further include a section of thinner material to allow high resolution imaging that often requires a shorter depth of focus lens, referred to as a flexible window 412. In one example, the flexible window 412 comprises PDMS having a thickness between about 0.1 mm and about 1 mm. Such a flexible window 412 may be pliable and retains known radiative transport properties. In such an example, the imaging device 402 may be positioned adjacent to the flexible window 412. Such a flexible window positioned adjacent to the imaging system 402 may enable measurements of, mechanical force, stiffness and elastic properties to further assess optomechanical integrity while the biological tissue sample remains sealed within the fluidic device 100. Radiative properties of such flexible windows will permit direct, quantitative measurement of local forces, stiffnesses, densities and elastic properties of the biological tissue sample, in addition to optical measurements.

In one example, positioning the biological tissue sample in the first channel 102 comprises inserting a needle into the first channel 102 and expelling the biological tissue sample from the needle. In such an example, the input interface 130 of the first end 104 of the first channel 102 may include a one-way septum to provide a sealed interface between the first channel 102 and the exterior of the fluidic device 100. In such an example, a pathologist can pass the biological tissue sample from a coring needle, through the input interface 130, and into the first channel 102. In such an example, the coring needle may be attached to a formalin-filled syringe prior to the deposition of the biological tissue sample into the fluidic device 100. In this fashion, fixative may be continuously diffusing into the biological tissue sample while the coring needle's contents are gently positioned into the first channel using formalin fluid flow from the syringe. Therefore the fluid that is used primarily for positioning the tissue sample can also have a second function, such as chemically fixing the biological tissue sample. For example, the fluid can be used to stain or label the tissue that provides selective optical contrast, such as adding absorptive stains (e.g. hematoxylin and eosin), fluorescence stains (e.g. Hoechst) or chemicals that reduce tissue optical scattering (e.g. glycerol). The biological tissue sample may be substantially cylindrical, and the first channel 102 has a cross-sectional height that is about 10% to about 20% greater than a cross- sectional height of the biological tissue sample or needle.

In another example, positioning the biological tissue sample in the first channel 102 comprises (i) providing a second fluid to the first channel to contact the biological tissue sample, where a flow rate of the second fluid through the first channel 102 is greater than a threshold flow rate, and where the biological tissue sample passes through the first channel 102 when the flow rate is greater than the threshold flow rate, and (ii) once the biological tissue sample is positioned adjacent to the opening 114 fluidically connecting the first channel 102 and the second channel 108, reducing the flow rate of the second fluid to be less than the threshold flow rate. To provide calibrated fluid flow, the pressure provided by pump(s) 128 to the second channel openings 1 10, 112 will be at a calibrated difference which is affected by fluid viscosity. Parallel channels such as 108 and 136 may provide equal flow or different flow rates to rotate the tissue sample. The flow rates may be adjusted based on the imaging performance of the tissue sample in the first channel 102 based on the imaging system 402 and processors 404. In such an example, the first fluid and the second fluid may be selected from a group consisting of optically clear gels, water, concentrated sucrose, glycerol-based saturated solutions/gels, dimethyl sulfoxide-based saturated solutions/gels, polyethylene glycol, and dextrose. The function of these fluids are to impart rotational forces onto the tissue sample and surrounding fluid of various viscosity without impairing the ability to optically image. Again, there can be a secondary function for this fluid with the addition of dyes for staining the tissue for absorptive, reflectance, or fluorescence imaging and with chemicals that reduce light scattering from the biological tissue. The threshold flow rate for aqueous solution is about 5 mL/min in the first channel 102. The flow rate in the second channel 108 may range from about 0.1 mL/min to about 10 mL/min.

In one example, the program instructions are further executable by the at least one processor to cause the fluidic device to (i) rotate, via the first fluid in the second channel, the biological tissue sample to a plurality of angular positions, (ii) capture, via the imaging device, one or more images of the biological tissue sample at each of the plurality of angular positions, and (iii) sum each image to create a three-dimensional image of the biological tissue sample. Summing each image to create the three-dimensional image of the biological tissue sample may include applying a stitching algorithm. The stitching algorithm may take in raw images from an imaging system such as above and output a stitching image. This may involve two steps: calculating shifting value between two images with overlaps, and stitching image using shifting value in two-dimensions. Rotating the biopsy within the first channel 102 by adding transverse flow to the second channel 108 is preferred so that the stationaiy imaging system 402 can continuously capture the image and then process the image through the stitching algorithm. The stitching algorithm may be performed by the system 400 and/or the computing device 602 described in additional detail below.

In another example, the program instructions are further executable by the at least one processor to cause the system to (i) rotate, via the first fluid in the second channel, the biological tissue sample to a plurality of angular positions, (ii) capture, via the imaging device, a video of the biological tissue sample at each of the plurality of angular positions, and (iii) create, using the video of the biological tissue sample, a three-dimensional image of the biological tissue sample. Figure 5 is a block diagram of an example method for preparing and transporting a biological tissue sample for pathology. Method 500 shown in Figure 5 presents an embodiment of a method that could be used by the fluidic devices 100 described in Figures 1- 3H or the system 400 described in Figure 4, as examples. Method 500 may include one or more operations, functions, or actions as illustrated by one or more of blocks 502-504. Although the blocks are illustrated in a sequential order, these blocks may also be performed in parallel and/or in a different order than those described herein. Also, the various blocks may be combined into fewer blocks, divided into additional blocks, and'Or removed based upon the desired implementation.

In addition, for the method 500 and other processes and methods disclosed herein, the block diagram shows functionality and operation of one possible implementation of present embodiments. In this regard, each block may represent a module, a segment, or a portion of program code, which includes one or more instructions executable by a processor or computing device for implementing specific logical functions or steps in the process. The program code may be stored on any type of computer readable medium, for example, such as a storage device including a disk or hard drive. The computer readable medium may include non-transitory computer readable medium, for example, such as computer-readable media that stores data for short periods of time like register memory, processor cache and Random Access Memory (RAM). The computer readable medium may also include non-transitory media, such as secondary or persistent long term storage, like read only memory (ROM), optical or magnetic disks, compact-disc read only memory (CD-ROM), for example. The computer readable media may also be any other volatile or non-volatile storage systems. The computer readable medium may be considered a computer readable storage medium, for example, or a tangible storage device.

Initially, at block 502, the method 500 includes positioning a biological tissue sample in the first channel 102 of the fluidic device 100 of Figures 1-3H adjacent the opening 114 fluidically connecting the first channel 102 and the second channel 108. In one example, positioning the biological tissue sample in the first channel comprises inserting a needle into the first channel and expelling the biological tissue sample from the needle. In another example, positioning the biological tissue sample in the first channel comprises (i) providing a second fluid to the first channel to contact the biological tissue sample, wherein a flow rate of the second fluid through the first channel is greater than a threshold flow rate, and wherein the biological tissue sample passes through the first channel when the flow rate is greater than the threshold flow rate, and (ii) once the biological tissue sample is positioned adjacent to the opening fluidically connecting the first channel and the second channel, reducing the flow rate of the second fluid to be less than the threshold flow rate. In the case of a sample of biological tissue that is not structurally interconnected, then the tangential flow of fluid creates a rotational motion of both the fluid and the tissue fragments, cellular and extracellular components in the first channel. As such, the fluidic device 100 can rotate cells and tissue fragments that may become disassociated with the bulk of the tissue biopsy, which is common in FNAB, but also true for the most diagnostic of CNB since cancerous tissue is often softer than healthy tissue.

At block 504, the method 500 includes providing a first fluid to the second channel 108 to tangentially contact the biological tissue sample to thereby rotate the biological tissue sample in the first channel 102.

Figure 6 illustrates an example schematic drawing of a computer network infrastructure. In one system 600, a computing device 602 communicates with the fluidic device 100 and/or the system 400 using a communication link 604, such as a wired or wireless connection. The computing device 602 may be any type of device that can receive data and display information corresponding to or associated with the data. For example, the computing device 602 may be a mobile phone, a tablet, or a personal computer as examples.

Thus, the computing device 602 may include a display system 606 comprising a processor 608 and a display 610. The display 610 may be, for example, an optical see- through display, an optical see-around display, or a video see-through display. The processor 608 may receive data from the fluidic device 100 and/or the system 400, and configure the data for display on the display 610. Depending on the desired configuration, processor 608 can be any type of processor including, but not limited to, a microprocessor, a microcontroller, a digital signal processor, or any combination thereof.

The computing device 602 may further include on-board data storage, such as memory 612 coupled to the processor 608. The memory 612 may store software that can be accessed and executed by the processor 608, for example. Further, processor 608 may receive data from the fluidic device 100 and/or the system 400, and configure the data for storage in the memory 612. The memory 612 can include any type of memory now known or later developed including but not limited to volatile memory (such as RAM), non-volatile memory (such as ROM, flash memory, etc.) or any combination thereof.

According to an example embodiment, the computing device 602 may include program instructions that are stored in the memory 612 (and/or possibly in another datastorage medium) and executable by the processor 608 to facilitate the various functions described herein. Although various components of the system 600 are shown as distributed components, it should be understood that any of such components may be physically integrated and/or distributed according to the desired configuration of the computing system.

The fluidic device 100 and/or the system 400 and the computing device 602 may contain hardware to enable the communication link 604, such as processors, transmitters, receivers, antennas, etc.

In Figure 6, the communication link 604 is illustrated as a wireless connection; however, wired connections may also be used. For example, the communication link 604 may be a wired link via a serial bus such as a universal serial bus or a parallel bus. A wired connection may be a proprietary connection as well. The communication linlc 604 may also be a wireless connection using, e.g., Bluetooth® radio technology, communication protocols described in IEEE 802.1 1 (including any IEEE 802.11 revisions), Cellular technology (such as GSM, CDMA, UMTS, EV-DO, WiMAX, or LTE), or Zigbee® technology, among other possibilities.

It should be understood that arrangements described herein are for purposes of example only. As such, those skilled in the art will appreciate that other arrangements and other elements (e.g. machines, interfaces, functions, orders, and groupings of functions, etc.) can be used instead, and some elements may be omitted altogether according to the desired results. Further, many of the elements that are described are functional entities that may be implemented as discrete or distributed components or in conjunction with other components, in any suitable combination and location, or other structural elements described as independent structures may be combined.

While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the toe scope being indicated by the following claims, along with the full scope of equivalents to which such claims are entitled. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

Since many modifications, variations, and changes in detail can be made to the described example, it is intended that all matters in the preceding description and shown in the accompanying figures be interpreted as illustrative and not in a limiting sense. Further, it is intended to be understood that the following clauses (and any combination of the clauses) further describe aspects of the present description.