Devices and methods enabling cells to undergo both visual and molecular diagnostics

Abstract

Devices and methods that enable loose cells to undergo both visual and molecular diagnostics are disclosed herein. In an embodiment, a microfluidic chip includes an input area, a viewing area, an output area and a filter. The input area is configured to receive cells obtained from a patient. The viewing area is in fluid communication with the input area. The viewing area is configured to enable a user to view the cells received at the input area. The output area is in fluid communication with the input area and the viewing area such that fluid mixed with the cells can flow from the input area, through the viewing area, to the output area. The filter is located between the viewing area and the output area, the filter configured to allow the fluid mixed with the cells to flow into the output area while preventing at least some of the cells from flowing into the output area.

Description

DEVICES AND METHODS ENABLING CELLS TO UNDERGOBOTH VISUAL AND MOLECULAR DIAGNOSTICSBACKGROUNDPriority Claim

[0001] This application claims priority to U.S. Patent Application No. 18 / 782,937, filed July 24, 2024. entitled ‘"Devices and Methods Enabling Cells to Undergo Both Visual and Molecular Diagnostics,” the entire contents of which is incorporated herein by reference and relied upon.Technical Field

[0002] The present disclosure generally relates to devices and methods that enable cells to undergo both visual and molecular diagnostics. More specifically, the present disclosure generally relates to devices and methods enabling a fine needle aspirate sample, or loose cells generated by “touch prep” following a core needle biopsy, to be analyzed visually on a microfluidic chip and then outputted from the microfluidic chip for a molecular diagnostic process.Background Information

[0003] Solid tumor diagnostic procedures sometimes involve a solid tissue biopsy, most often obtained through a hollow needle approximately 1 mm wide, a procedure known as a core needle biopsy (CNB). Other times they involve a less invasive procedure for harvesting cells from a target tissue of interest by way of a thin needle only wide enough to obtain loose cells, without regard for obtaining a solid piece of tissue, called a fine needle aspiration (FNA). FNA procedures have become commonplace in cancer diagnostic workups, and are portrayed to patients as simple procedures with low risk of adverse events. A specialized syringe is used, and the advantage for the patient is that this is a less invasive way of obtaining a pathology diagnosis. In the current standard of care, the extracted cells are placed on a glass slide and remain there for visual examination, known as a cytology examination. Cells from the FNA procedure are smeared on to a glass slide, stained and in some cases, cover-slipped. Figures 1 A to 1C illustrate this process, showing cells harvested from the FNA procedure placed on a standard glass slide, smeared between two sides, and then covered with a coverslip and sent for microscopic examination. The cells can then be examined under a microscope. In an alternate situation in which loose cells on a glass slide are evaluated visually (via microscopy),some clinicians who perform core needle biopsies will take the solid tissue core harvested and, before subjecting it to the preservative formalin, gently touch the tissue to a glass slide. This so-called “touch prep” procedure leaves cells on the glass slide for staining and microscopic examination.

[0004] These existing methods do not provide any information about the genes (the DNA) of the patient’s cells. If the oncologist treating the patient desires any molecular studies (e.g. genomic screening of next generation sequencing) to be performed on the patient’s cells, the only way to accomplish that is to (a) subject the patient to a second FNA procedure to harvest more cells, or (b) a tedious, expensive, and error-prone process to gain access to the cells fixed under the glass slide and selectively capture them, wherein a user needs to immerse the glass slide in an organic solvent like xylene (dangerous) to loosen the coverslip, remove it. then scrape the cells into another tube (potential source of losing cells) or use a laser capture microdissection device (expensive) for molecular testing.SUMMARY

[0005] Diagnostic testing modalities have expanded in recent years to include an increased number of tests to identify molecular changes. Visual examination of cells on a glass slide under a microscope remains one of the most useful (and time-honored) diagnostic techniques in medicine, and comprises the basis for the field of pathology. The present disclosure provides devices and methods that enable both of visual and diagnostic modalities from a single FNA procedure. As a secondary function, devices and methods disclosed herein also provide the user with a simple way to know that the FNA specimen contains cells (the intent of a FNA procedure) immediately upon withdrawing the specimen from the patient. That information has the advantages that it (a) helps avoid unnecessary additional needle passes (if the first specimen contains adequate cells), and (b) helps avoid ending a procedure without obtaining tumor cells (if the first specimen does not contain adequate cells). The devices and methods of the present disclosure thus provide a dual purpose: (1) confirming “specimen adequacy” or “representative diagnosis” through examination on the chip, and quick recovery of those same cells or their nucleic acids for (2) molecular testing.

[0006] No similar product currently exists on the market. Instruments to sort cells exist, but they do not allow cytology -quality examination. An advantage of using the devices and methods of the present disclosure is that cells harvested in a FNA procedure (or “touch prep” following a CNB procedure) that would otherwise be entombed in a glass slide are instead immediately available for molecular testing after they have been examined via microscopy. Insome instances, when molecular studies are requested, the cells from an FNA are the only place where there is enough material to test. Recovering these cells can be an expensive process that can take days, as it involves removing the glued-on coverslip and may require laser capture microdissection.

[0007] The embodiments described herein can be used after an FNA procedure, or a “touch prep" subsequent to a CNB procedure, is performed. The embodiments provide a convenient simple-to use device that takes a fine needle aspirate or “touch prep” sample and (1) confirms “specimen adequacy” or “representative diagnosis” through visual examination, and (2) enables quick recovery' of those same cells or their nucleic acids for molecular testing, then also (3) retains and routes those cells for their status quo usage - preservation of their cytologic image for microscopic examination. In an embodiment, the disclosed devices and methods capture cells using immunomagnetic beads, cause the cells to travel through a microfluidic channel to an area for viewing or scanning, then enable recovery of the cells for molecular analysis. The embodiments described herein are applicable and apply equally well to either: (a) loose cells on a glass slide produced by a FNA procedure, or (b) loose cells on a glass slide produced by a “touch prep” subsequent to a CNB.

[0008] The disclosed devices and methods can be used in a clinical environment, for example, in instances where a pathologist is called into a radiology7procedure (fine needle aspiration, or core needle biopsy) and is being asked to assess (1) adequacy and (2) confirmation that diagnostic material is present (tumor cells). More specifically, the presently disclosed devices and methods provide microfluidic chip systems and technologies for interventional radiologists and other clinicians who perform fine needle aspiration (FNA) procedures and the pathologists who assist them with diagnostic methodologies to (a) ascertain whether an FNA procedure has yielded adequate cellular material, and to (b) segregate cells in a fluid suspension of the harvested cells into one or more aliquots for microscopic examination with recovery7of those same cells for molecular or genomic testing. The microfluidic chip can be about the size of a standard glass slide for a microscope, with a linear channel that originates at a vertical cellular input silo, runs through a widened viewing area, and terminates in an upward / downward facing cellular output silo, along with a specialized supporting device that moves a magnet into and out of alignment with the widened viewing area. The purpose of the device is that cells harvested in a FNA procedure, or by way of a “touch prep” following a CNB procedure, thatwould otherwise be entombed in a glass slide and unavailable for molecular testing are instead available for molecular testing after they have been examined via microscopy.

[0009] A first aspect of the present disclosure is to provide a microfluidic chip enabling cells to undergo both a visual diagnostic and a molecular diagnostic. The microfluidic chip includes an input area, a viewing area, an output area and a filter. The input area is configured to receive cells obtained from a patient. The viewing area is in fluid communication with the input area. The viewing area is configured to enable a user to view the cells received at the input area. The output area is in fluid communication with the input area and the viewing area such that fluid mixed with the cells can flow from the input area, through the viewing area, to the output area. The filter is located between the viewing area and the output area, the filter configured to allow the fluid mixed with the cells to flow into the output area while preventing at least some of the cells from flowing into the output area.

[0010] A second aspect of the disclosure is to provide a method of enabling cells to undergo a visual diagnostic and be preserved for a molecular diagnostic. The method includes inputting the cells into an input area of a microfluidic chip, inputting a fluid into the input area of the microfluidic chip, applying pressure at the input area to cause the cells to flow into a viewing area of the microfluidic chip and the fluid to flow into an output area of the microfluidic trip, viewing the cells w ithin the viewing area, and withdrawing at least some of the cells from the viewing area back into the input area w hile at least some of the fluid remains in the output area.

[0011] A third aspect of the disclosure is to provide a microfluidic chip enabling cells to undergo both a visual diagnostic and a molecular diagnostic. The microfluidic chip includes a body, an input area, an output area, at least one microchannel, and a viewing area. The body includes an upper surface and a lower surface extending in a longitudinal direction from a first end to a second end and in a lateral direction from a first lateral side to a second lateral side. The input area includes an input silo configured to receive cells obtained from a patient. The output area includes an output silo. The design aligns the input silo and the output silo in fluid communication. The viewing area is in fluid communication with the at least one microchannel and is configured to enable the visual diagnostic of the cells that have flowed through the at least one microchannel.

[0012] A fourth aspect of the present disclosure is to provide a system including the microfluidic chip and / or a supportive device configured to serve as a platform from which the microfluidic chip can be mounted and aligned to a magnetic force with the viewing area.

[0013] A fifth aspect of the present disclosure is to provide a supportive device enabling cells to undergo both a visual diagnostic and a molecular diagnostic. The supportive device includesa microfluidic chip mount and an alignment arm. The microfluidic chip mount is configured to removably receive a microfluidic chip in an orientation in which cells can be deposited at an input area of the microfluidic chip and flow through the microfluidic chip via capillary action. The alignment arm includes a magnet and is configured to move with respect to the microfluidic chip mount to translate the magnet into and out of alignment with a viewing area of the microfluidic chip when the microfluidic chip is mounted on the microfluidic chip mount.

[0014] A sixth aspect of the present disclosure is to provide a system including the supportive device and / or the microfluidic chip having the input area and the viewing area.

[0015] A seventh aspect of the present disclosure is to provide a method enabling cells to undergo both a visual diagnostic and a molecular diagnostic. The method includes depositing cells attached to immunomagnetic beads into an input area in fluid communication with at least one microchannel such that the cells attached to the immunomagnetic beads flow from the input area through the at least one microchannel, aligning a magnetic force with a viewing area in fluid communication with the at least one microchannel so that the cells attached to the immunomagnetic beads collect in the viewing area for the visual diagnostic, and enabling the cells attached to the immunomagnetic beads to flow to an output area in fluid communication with the viewing area to be collected for the molecular diagnostic.

[0016] An eighth aspect of the present disclosure is to provide a system including the microfluidic chip and / or the supportive device described herein.

[0017] A ninth aspect of the present disclosure is to provide a method of using the microfluidic chip and / or the supportive device described herein.

[0018] Other objects, features, aspects and advantages of the apparatuses and methods disclosed herein will become apparent to those skilled in the art from the following detailed description, which, taken in conjunction with the annexed drawings, discloses exemplary embodiments of the disclosed apparatuses and methods.BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Referring now to the attached drawings which form a part of this original disclosure:

[0020] Figures 1 A to 1C illustrate an example embodiment of a prior art method of smearing cells harvested from an FNA procedure on a glass slide for analysis;

[0021] Figure 2 illustrates a top perspective view of a first example embodiment of a microfluidic chip in accordance with the present disclosure:

[0022] Figure 3 illustrates a top perspective exploded view of the microfluidic chip of Figure 2;

[0023] Figure 4 illustrates a cross-sectional view of the microfluidic chip of Figures 2 and 3 taken through lines IV -IV in Figure 2;

[0024] Figure 5 illustrates a top perspective view of a second example embodiment of a microfluidic chip in accordance with the present disclosure;

[0025] Figure 6 illustrates a bottom perspective view of the microfluidic chip of Figure 5;

[0026] Figure 7 a top perspective exploded view of the microfluidic chip of Figure 5;

[0027] Figure 8 illustrates a top perspective view of a third example embodiment of a microfluidic chip in accordance with the present disclosure;

[0028] Figure 9 illustrates a top perspective exploded view of the microfluidic chip of Figure 8;

[0029] Figure 10 illustrates a cross-sectional view of the microfluidic chip of Figures 8 and 9 taken through lines X-X in Figure 8;

[0030] Figure 11 illustrates a top perspective view of a fourth example embodiment of a microfluidic chip in accordance with the present disclosure;

[0031] Figure 12 illustrates a top perspective exploded view of the microfluidic chip of Figure 11;

[0032] Figure 13 illustrates a cross-sectional view of the microfluidic chip of Figures 10 and11 taken through lines XIII -XIII in Figure 11;

[0033] Figure 14 illustrates an example embodiment of a method of enabling cells to undergo a visual diagnostic and be preserved for a molecular diagnostic in accordance with the present disclosure;

[0034] Figures 15A and 15B illustrate example embodiments of certain of the steps of Figure 14 using a prototype of the microfluidic chip illustrated in Figures 2 to 4;

[0035] Figures 16A and 16B illustrate example embodiments of certain of the steps of Figure 14 using a prototype of the microfluidic chip illustrated in Figures 8 to 10;

[0036] Figures 17A and 17B illustrate example embodiments of certain of the steps of Figure12 using a prototy pe of the microfluidic chip illustrates in Figures 11 to 13;

[0037] Figures 18A to 18L illustrate example embodiments of the viewing window of the microfluidic chips disclosed herein under a microscope during the method of Figure 14;

[0038] Figure 19 illustrates a top perspective view of another example embodiment of a microfluidic chip in accordance with the present disclosure.

[0039] Figure 20 illustrates a top perspective view of another example embodiment of a microfluidic chip in a first orientation in accordance with the present disclosure;

[0040] Figure 21 illustrates a bottom perspective view of the microfluidic chip of Figure 20 in the first orientation;

[0041] Figure 22 illustrates a top perspective view of the microfluidic chip of Figures 20 and21 in a second orientation in accordance with the present disclosure.

[0042] Figure 23 illustrates atop perspective diagram of the microfluidic chip of Figures 20 to22 changing orientation in accordance with the present disclosure;

[0043] Figure 24 illustrates a top perspective view of an example embodiment of a mechanical attachment mechanism for a microfluidic chip in accordance with the present disclosure;

[0044] Figure 25 illustrates a top perspective view of an example embodiment of a supportive device in accordance with the present disclosure;

[0045] Figure 26 illustrates a top perspective view of the microfluidic chip of Figure 19 mounted on the supportive device of Figure 25; and

[0046] Figure 27 illustrates an example embodiment of a method of using a microfluidic chip and / or a supportive device in accordance with the present disclosure.DETAILED DESCRIPTION OF EMBODIMENTS

[0047] Selected embodiments will now be explained with reference to the drawings. It will be apparent to those skilled in the art from this disclosure that the following descriptions of the embodiments are provided for illustration only and not for the purpose of limiting the invention as defined by the appended claims and their equivalents.

[0048] Figures 2 to 13 illustrate several example embodiments of microfluidic chips 10, 110, 210, 310 configured in accordance with the present disclosure. The microfluidic chips 10, 110, 210, 310 are configured to maximize the clinical benefits of limited amounts of cellular material obtained by a FNA procedure or “touch prep” following a CNB procedure. More specifically, the microfluidic chips 10, 110, 210, 310 enable cells to undergo both a visual diagnostic and a molecular diagnostic. The visual diagnostic takes place while the cells are located within the microfluidic chip 10, 110, 210, 310 with the microfluidic chip 10, 110, 210, 310 then enabling the cells to be recaptured for subsequent molecular testing.

[0049] The microfluidic chips 10. 110, 210. 310 of Figures 2 to 13 include many of the same features, and like reference numerals have been used to identify like elements in most instances. A main difference between the microfluidic chips 10, 110, 210, 310 is the location of a respective filter 38, 138, 238, 338 as explained in more detail below. The microfluidic chip 10 of Figures 2 to 4 and the microfluidic chip 110 of Figures 5 to 7 locate the filter 38. 138 within the viewing area 36, 136. The microfluidic chip 210 of Figures 8 to 10 locates the filter 238within the outlet area 250. The microfluidic chip 310 of Figures 11 to 13 locates the filter 338 within a filter cavity 337 adjacent to and downstream of the viewing area 336. The microfluidic chips 10, 110, 210, 310 also include other differences in the locations and constructions of microchannels, vents and chambers. Those of ordinary skill in the art will recognize from this disclosure that the features of any of the microfluidic chips 10, 110, 210, 310, 410 described herein can be applied to any of the other microfluidic chips 10, 110, 210, 310, 410 described herein.

[0050] Figures 2 to 4 illustrate a first example embodiment of a microfluidic chip 10 which locates the filter 38 within the viewing area 36. As seen in Figure 2, the microfluidic chip 10 generally includes an elongated body 12 having an upper surface 13 and a lower surface 14. The upper surface 13 and the lower surface 14 extend in the longitudinal direction from a first end 15 to a second end 16 and in the lateral direction from a first lateral side 17 to a second lateral side 18.

[0051] As seen in Figure 3, the body 12 can be formed of various layers. In the illustrated embodiment, the microfluidic chip 10 is generally formed by one or more of a first (lower) layer 21. a second (intermediate / lower) layer 22, a third (intermediate) layer 23. a fourth (intermediate / upper) layer 24, a fifth (upper) layer 25, a sixth (intermediate / upper) layer 26 and a seventh (upper) layer 27. It should be understood by those of ordinary' skill in the art from this disclosure that the terms “first,’' “second.” “third,” etc. can be reordered or used interchangeably and are not intended to be limiting. For example, the “first” layer can also be described as the “second” or “third” layer, and vice versa. It should further be understood by those of ordinary' skill in the art from this disclosure that multiple layers can be combined into a single layer or individual layers can further be separated into multiple separate layers. The layers of the body 12 can be formed of various materials including, for example, glass, silicon, polymer or other suitable materials.

[0052] In the illustrated embodiment, the first layer 21 is a transparent layer which forms the lower surface 14 of the body 12. The transparent first layer 21 enables a user to view' through the lower surface 14 into the microchannels 30, 32, 34, the viewing area 36 and the inner area 56 of the output silo 52. In an embodiment, the first layer 21 is formed of 0.25 mm thick transparent acrylic film.

[0053] In the illustrated embodiment, the second layer 22 is an adhesive layer which adheres the first layer 21 to the third layer 23. In an embodiment, the second layer 22 is formed of double-sided pressure sensitive adhesive (PSA). In another embodiment, the second layer 22can be formed by applying another pe of adhesive between the first layer 21 to the third layer 23.

[0054] In the illustrated embodiment, the third layer 23 is a rigid part forming the majority of the height of the body 12. The third layer 23 also forms the majority of the chamber within the viewing area 36, the input silo 42 and the output silo 52. In an embodiment, the third layer 23 is a 3D printed slide. The third layer 23 can be made of polycarbonate, polypropylene, polymethyl methacrylate, or any plastic material. The third layer 23 can also be formed of other methods besides 3D printing, for example, by injection molding, blow molding, thermoforming, compression molding, transfer molding, CNC machining, casting, or other suitable methods.

[0055] In the illustrated embodiment, the fourth layer 24 is an adhesive layer which adheres the third layer 21 to the fifth layer 25. Similarly, the sixth layer 26 is an adhesive layer which adheres the third layer 21 to the seventh layer 27. In an embodiment, the fourth layer 24 and the sixth layer 26 are formed of double-sided PSA. In another embodiment, the fourth layer 24 and the sixth layer 26 can be formed by applying another type of adhesive between the respective bordering layers.

[0056] In the illustrated embodiment, the fifth layer 25 is a transparent layer which forms part of the upper surface 13 of the body 12. The transparent fifth layer 25 enables a user to view through the upper surface 13 into the output silo 52. In an embodiment, the fifth layer 25 is formed of 0.25 mm thick transparent acrylic film.

[0057] In the illustrated embodiment, the seventh layer 27 is a transparent layer which forms part of the upper surface 13 of the body 12. The transparent seventh layer 27 forms a viewing window for the viewing area 36, enabling a user to view the cells within the viewing area 36 from above. In an embodiment, the seventh layer 27 is formed of 0.25 mm thick transparent acrylic film.

[0058] The microfluidic chip 10 also includes a filter 38. The filter 38 is configured to filter at least some cells input into the microfluidic chip 10 from fluid mixed with the cells as the fluid and cells travel through the microfluidic chip 10, as explained in more detail below. In an embodiment, the filter 38 is formed of an 18-micron filter mesh material.

[0059] The microfluidic chip 10 also includes an air vent cover 39. The air vent cover 39 is attached to the fifth layer 25.

[0060] The microfluidic chip 10 includes at least one microchannel 30. In the illustrated embodiment, the at least one microchannel 30 includes a first microchannel 32 and a second microchannel 34. The microfluidic chip 10 also includes a viewing area 36. The viewing area36 is in fluid communication with the microchannel(s) 30. The viewing area 36 is configured to enable a visual diagnostic of the cells that have flowed through the at least one microchannel 30.

[0061] As seen in Figures 2 to 4, the first microchannel 32 and the second microchannel 34 extend in the longitudinal direction of the body 12. The viewing area 36 is located between the first microchannel 32 and the second microchannel 34 in the longitudinal direction. The first microchannel 32 and the second microchannel 34 are longer than the viewing area 36 in the longitudinal direction. The viewing area 36 is wider than the first microchannel 32 and the second microchannel 34 in the lateral direction. The first microchannel 32 and the second microchannel 34 are each in fluid communication with the viewing area 36, such that fluid can travel through the first microchannel 32 to the viewing area 36 and then from the viewing area 36 through the second microchannel 34.

[0062] In the illustrated embodiment, the first microchannel 32 includes a first portion 32a and a second portion 32b. As seen in Figure 4, the second portion 32b is located vertically higher than the first portion 32a. As seen in Figure 3, the second layer 22 forms the first portion 32a, and the third layer 23 forms the second portion 32b. More specifically, the first portion 32a is formed as an elongated cutout through the second layer 22, and the second portion 32b is formed as an elongated cutout into the upper surface of the third layer 23. The first layer 21 forms the lower surface of the first portion 32a, and the third layer 23 forms the upper surface of the first portion 32a. The third layer 23 forms the lower surface of the second portion 32b, and the sixth layer 26 or the seventh layer 27 forms the upper surface of the second portion 32b.

[0063] In the illustrated embodiment, the second microchannel 34 is formed as an elongated cutout through the second layer 22. The second microchannel 34 is therefore vertically even with the first portion 32a of the first microchannel 32 and vertically below the second portion 32b of the first microchannel 32. The first layer 21 forms the lower surface of the second microchannel 34, and the third layer 23 forms the upper surface of the second microchannel 34.

[0064] In the illustrated embodiment, the viewing area 36 includes a cutout 36a in the third layer 23, a cutout 36b in the sixth layer 26 and an upper viewing window' formed by the seventh layer 27. As seen in Figure 4, the cutout 36a and the cutout 36b form an upper viewing chamber 36c beneath a viewing window 36d formed by the seventh layer 27 and above the filter 38. The viewing window 36d is the portion of the seventh layer 27 located directly above the upper chamber 36c. The viewing area 36 also includes a lower chamber 37 located below the upperchamber 36c and the filter 38. The lower chamber 37 is formed by a cutout in the second layer 22, with the first layer 21 providing the lower surface of the lower chamber 37. The filter 38 is located between the upper chamber 36c and the lower chamber 37. More specifically, the filter 38 is located between the upper chamber 36c and the lower chamber 37 in the vertical direction.

[0065] The microfluidic chip 10 includes an input area 40. The input area 40 includes a first (or input) silo 42. The first silo 42 is configured to receive cells obtained from a patient so that the cells can undergo the visual diagnostic. The first silo 42 is also configured to receive fluid with dye intended to make cells visible via microscopy and / or clear fluid during the method of use discussed in more detail below. The first silo 42 extends upward from the third layer 23 at the first end 15 of the body 12. More specifically , the first silo 42 includes an outer wall 44 that extends outward from the upper surface of the third layer 23. The first silo 42 includes an inner area 46 located within the outer surface 44. The inner area 46 is in fluid communication with the first microchannel 32 at the lower end thereof, as seen in Figure 4. In use, a user (e.g., clinician or interventional radiologist) can place a needle or pipette containing cells from an FNA procedure into the input silo 42 and deposit the cells, as well as dyed fluid and / or clear fluid, so that the cells flow through the first microchannel 32 to the viewing area 36. A common plastic syringe applied to the first silo 42 can be used to (1) push the initial fluid sample taken from the patient into the input port, (2) push more fluid (non-dyed) to rinse away the dye after the cells have been dyed, and (3) pull the cells back out of the first silo 42 to recover them for molecular testing.

[0066] The microfluidic chip 10 also includes an output area 50. The output area 50 is an overflow area and includes a second (or output / overflow) silo 52. The second silo 52 is configured to permit an overflow of the fluid input at the input silo 42. The second silo 52 extends upward from the third layer 23 at the second end 16 of the body 12. More specifically, the second silo 52 includes an outer surface 54 that extends outward from the upper surface of the third layer 23. The output silo 52 includes an inner area 56 located within the outer surface 54. The inner area 56 is in fluid communication with the second microchannel 34 and receives the overflow fluid during the method of use discussed below. As seen in Figure 4, fluid enters the inner area 56 at an entry point 55 that is located at or near the upper part of the output surface 54, and vertically above each of the first microchannel 32, the second microchannel 34 and the viewing area 36, which causes the fluid that fills the inner area 56 during the method of use discussed below to remain in the inner area 56 when the cells are withdrawn from the input area 40 at the end of the method. The purpose of the inner area 56 is to provide a way for some of the fluid with dye to be sequestered away, because cells are difficult to visualizewhile dye is all around them. Thereby, the device enables the user to prepare cells for microscopic visualization in the most effective way (1) exposed them to dye, so their membranes become dark, and then (2) wash away the excess dye, so that the space around the cells is clear.

[0067] As seen in Figures 3 and 4, the output surface 54 surrounding the output area 56 further forms an outlet microchannel 57 and an air vent channel 58. The outlet microchannel 57 includes a vertically extending microchannel 59 and a longitudinally extending microchannel 60. The at least one microchannel 30 thus includes the vertically extending microchannel 59 and the longitudinally extending microchannel 60. The vertically extending microchannel 59 extends vertically through the output surface 54 and fluidly connects the second microchannel 34 and the longitudinally extending microchannel 60. The longitudinally extending microchannel 60 fluidly connects the vertically extending microchannel 59 and the inner area 56 of the output silo 52 at the entry point 55. In an embodiment, the vertically extending microchannel 59 and / or the longitudinally extending microchannel 60 can be angled instead of extending straight vertically or laterally, or can be combined or further separated into additional microchannels.

[0068] In the illustrated embodiment, the inner area 56 is formed by a cutout 56a in the second layer 22, a cutout 56b in the third layer 23 and a cutout 56c in the fourth layer 24, as seen in Figure 3. The first layer 21 forms the bottom surface of the inner area 56 and the fifth layer 25 forms the upper surface of the inner area 56. Since the fifth layer 25 is transparent, the fifth layer 25 also creates a viewing window allowing a user to view the fluid within the inner area 56 of the output silo 52.

[0069] A primary purpose inner area 56 (and the inner areas 156, 256, 356 discussed below) is to provide a way for some of the fluid with dye to be sequestered away, because cells are difficult to visualize while dye is all around them. Thereby, the inner area 56 enables the user to prepare cells for microscopic visualization and in the most effective way (1) expose them to dye, so their membranes become dark, and then (2) wash away the excess dye, so that the space around the cells is clear.

[0070] In the illustrated embodiment, the vertically extending microchannel 59 is formed by a cutout through the height of the third layer 23, while the longitudinally extending microchannel 60 is formed by a cutout 60a in the upper surface of the third layer 23 and a cutout 60b through the fourth layer 24. The third layer 23 forms the bottom surface of the longitudinally extending microchannel 60 and the fifth layer 25 forms the upper surface of the vertically extending microchannel 59 and the longitudinally extending microchannel 60.

[0071] In the illustrated embodiment, the air vent channel 58 is formed by a vent channel 61 and the vent cover 39. The vent channel 61 is formed by a cutout 61a in the upper surface of the third layer 23, a cutout 61b through the fourth layer 24, and a smaller cutout 61c through the fifth layer 25. The third layer 23 forms the bottom surface of the vent channel 61 and the fifth layer 25 forms the upper surface of the vent channel 61 except at the cutout 61c. The air vent cover 39 is attached over the cutout 61c of the vent channel 61 so as to permit air to escape the inner area 56 through the air vent 58.

[0072] Figures 5 to 7 illustrate a second example embodiment of a microfluidic chip 110 which locates the filter 138 within the viewing area 136. As seen in Figures 5 and 6, the microfluidic chip 110 generally includes an elongated body 112 having an upper surface 113 and a lower surface 114. The upper surface 113 and the lower surface 114 extend in the longitudinal direction from a first end 1 15 to a second end 116 and in the lateral direction from a first lateral side 117 to a second lateral side 118.

[0073] As seen in Figure 7, the body 112 can be formed of various layers. In the illustrated embodiment, the microfluidic chip 110 is generally formed by one or more of a first (lower) layer 121, a second (intermediate / lower) layer 122. a third (intermediate) layer 123, a fourth (intermediate / upper) layer 124, a fifth (upper) layer 125, a sixth (intermediate / upper) layer 126 and a seventh (upper) layer 127. As with the microfluidic chip 10, the terms “first,” “second,” “third,” etc. can be used interchangeably, and layers can be combined or further separated.

[0074] In the illustrated embodiment, the first layer 121 is a transparent layer which forms the lower surface 1 14 of the body 12. As seen in Figure 6, the transparent first layer 121 enables a user to view through the lower surface 114 into the microchannels 130, 132, 134 and / or the viewing area 136. In an embodiment, the first layer 121 is formed of 0.25 mm thick transparent acrylic film.

[0075] In the illustrated embodiment, the second layer 122 is an adhesive layer which adheres the first layer 121 to the third layer 123. In an embodiment, the second layer 122 is formed of double-sided pressure sensitive adhesive (PSA). In another embodiment, the second layer 122 can be formed by applying another type of adhesive between the first layer 121 to the third layer 123.

[0076] In the illustrated embodiment, the third layer 123 is a rigid part forming the majority of the height of the body 112. The third layer 123 also forms the majority of the chamber within the viewing area 136, the input silo 142 and the output silo 152. In an embodiment, the third layer 123 is a 3D printed slide. The third layer 123 can be made of polycarbonate, polypropylene, polymethyl methacrylate, or any plastic material. The third layer 123 can alsobe formed of other methods besides 3D printing, for example, by injection molding, blow molding, thermoforming, compression molding, transfer molding, CNC machining, casting, or other suitable methods.

[0077] In the illustrated embodiment, the fourth layer 124 is an adhesive layer which adheres the third layer 121 to the fifth layer 125. Similarly, the sixth layer 126 is an adhesive layer which adheres the third layer 121 to the seventh layer 127. In an embodiment, the fourth layer 124 and the sixth layer 126 are formed of double-sided PSA. In another embodiment, the fourth layer 24 and the sixth layer 126 can be formed by applying another type of adhesive between the respective bordering layers.

[0078] In the illustrated embodiment, the fifth layer 125 is a transparent layer which forms part of the upper surface 113 of the body 112. The transparent fifth layer 125 enables a user to view through the upper surface 113 into the output silo 152. In an embodiment, the fifth layer 125 is formed of 0.25 mm thick transparent acrylic film.

[0079] In the illustrated embodiment, the seventh layer 127 is a transparent layer which forms part of the upper surface 113 of the body 112. The transparent seventh layer 127 forms a viewing window for the viewing area 136. enabling a user to view the cells within the viewing area 136 from above. In an embodiment, the seventh layer 127 is formed of 0.25 mm thick transparent acrylic film.

[0080] The microfluidic chip 110 also includes a filter 138. The filter 138 is configured to filter at least some cells input into the microfluidic chip 110 from fluid mixed with the cells as the fluid and cells travel through the microfluidic chip 1 10, as explained in more detail below. In an embodiment, the filter 138 is formed of an 18-micron filter mesh material.

[0081] The microfluidic chip 110 also includes an air vent cover 139. The air vent cover 139 is attached to the fifth layer 125.

[0082] The microfluidic chip 110 includes at least one microchannel 130. In the illustrated embodiment, the at least one microchannel 130 includes afirst microchannel 132 and a second microchannel 134. The microfluidic chip 110 also includes a viewing area 136. The viewing area 136 is in fluid communication with the microchannel(s) 130. The viewing area 136 is configured to enable a visual diagnostic of the cells that have flowed through the at least one microchannel 130.

[0083] As seen in Figures 5 to 7, the first microchannel 132 and the second microchannel 134 extend in the longitudinal direction of the body 112. The viewing area 136 is located between the first microchannel 132 and the second microchannel 134. The first microchannel 132 and the second microchannel 134 are longer than the viewing area 136 in the longitudinal direction.The viewing area 136 is wider than the first microchannel 132 and the second microchannel 134 in the lateral direction. The first microchannel 132 and the second microchannel 134 are each in fluid communication with the viewing area 136, such that fluid can travel through the first microchannel 132 to the viewing area 136 and then from the viewing area 136 through the second microchannel 134.

[0084] Similar to the first microchannel 32 discussed above, in the illustrated embodiment, the first microchannel 132 includes a first portion 132a and a second portion 132b. The second portion 132b is located vertically higher than the first portion 132a. As seen in Figures 5 and 6, the first portion 32a is cutout into the lower surface of the third layer 123, and the second portion 132b is cutout into the upper surface of the third layer 123. The first portion 132a can also be cutout through the second layer 122, similar to with the first microchannel 32 discussed above. The first layer 121 can form the lower surface of the first portion 32a, and the third layer 123 can form the upper surface of the first portion 132a. The third layer 123 can form the lower surface of the second portion 132b, and the sixth layer 126 or the seventh layer 127 can form the upper surface of the second portion 132b.

[0085] In the illustrated embodiment, the second microchannel 134 is formed as an elongated cutout into the lower surface of the third layer 123. The second microchannel 134 is therefore vertically even with the first portion 132a of the first microchannel 132 and vertically below the second portion 132b of the first microchannel 132. Here, the second microchannel also begins in the direction of the second end 116 and then curves back towards the first end 115. The first layer 121 can form the lower surface of the second microchannel 134, and the third layer 123 can form the upper surface of the second microchannel 134.

[0086] The viewing area 136 is formed substantially the same as the viewing area 36 discussed above. In the illustrated embodiment, the viewing area 136 includes a cutout 36a in the third layer 23. The viewing area can also be formed with a cutout in the sixth layer 126 and an upper viewing window formed by the seventh layer 127. Similar to above, the cutout 136a can form an upper viewing chamber beneath a viewing window formed by the seventh layer 127 and above the filter 138. The viewing window is the portion of the seventh layer 127 located directly above the upper chamber. Similar to above, the viewing area 136 can also include a lower chamber located below the upper chamber and the filter 138. The lower chamber can be formed, for example, by a cutout in the second layer 122, with the first layer 121 providing the lower surface of the lower chamber. The filter 138 can be located between the upper chamber and the lower chamber. More specifically, the filter 138 can be located between the upper chamber and the lower chamber in the vertical direction as discussed above.

[0087] The microfluidic chip 110 includes an input area 140. The input area 140 includes a first (or input) silo 142. The first silo 142 is configured to receive cells obtained from a patient so that the cells can undergo the visual diagnostic. The first silo 142 is also configured to receive fluid with dye intended to make cells visible via microscopy and / or clear fluid during the method of use discussed in more detail below. The first silo 142 extends upward from the third layer 123 at the first end 115 of the body 112. More specifically, the first silo 142 includes an outer wall 144 that extends outward from the upper surface of the third layer 123. The first silo 142 includes an inner area 146 located within the outer surface 144. The inner area 146 is in fluid communication with the first microchannel 132 at the lower end thereof, marked by microchannel entry' point 132c in Figure 4. In use, a user (e g., clinician or interventional radiologist) can place a needle or pipette containing cells from an FNA procedure into the input silo 142 and deposit the cells, as well as dyed fluid and / or clear fluid, so that the cells flow through the first microchannel 132 to the viewing area 136.

[0088] The microfluidic chip 110 also includes an output area 150. The output area 150 is an overflow area and includes a second (or output / overfloyv) silo 152. The second silo 152 is configured to permit an overflow of the fluid input at the input silo 142. The second silo 152 extends upward from the third layer 123 at the first end 115 of the body 1 12, adjacent to and offset from the input silo 142. This configuration allows the user to place the microfluidic chip 110 on a standard microscope and rotate the rotating objective lenses without hitting any of the parts of the microfluidic chip 110.

[0089] The output silo 152 includes a first inner area 156a and a second input area 156b located within the outer surface 154. The first inner area 156a and the second input area 156b are separated by an inner wall 156c with an aperture 156d at the top. The first inner area 156a is an overflow / sedimentation chamber for capturing larger sedimentation particles. The second input area 156b is for fluid only, which overflows from the first inner area 156a into the second inner input area 156b via the space within the aperture 156d.

[0090] The inner areas 156a, 156b are in fluid communication with the second microchannel 34 and receive overflow fluid during the method of use discussed below. As with the output silo 52 discussed above, fluid enters the first inner area 156 at an entry’ point 155 that is located at or near the upper part of the output surface 154, and vertically above each of the first microchannel 132, the second microchannel 134 and the viewing area 136, which causes the fluid that fills the first inner area 156a and the second inner area 156b during the method of use discussed below to remain in the first inner area 156a and the second inner area 156b when the cells are withdrawn from the input area 140 at the end of the method. As with the microfluidicchip 10 discussed above, the output surface 154 can further include an outlet microchannel formed by a vertically extending microchannel and a longitudinally extending microchannel. Additionally, the inner areas 156a, 156b can be formed by cutouts in one or more of the second layer 122, the third layer 123 and the fourth layer 124, while the fifth layer can create a viewing window therein.

[0091] In the illustrated embodiment, an air vent 158 is further formed by a cutout 161a in the fourth layer 124. a cutout 161b in the fifth layer 125 and the air vent cover 139. Here, the cutouts 161a, 161b forming the air vent 158 are located directly above the first inner area 156a of the output silo 152. The air vent cover 139 is attached over the cutouts 161a, 161b as to permit air to escape the inner area 156 through the air vent 158.

[0092] Figures 8 to 10 illustrate a third example embodiment of a microfluidic chip 210 which locates the filter 238 within the outlet area 250. As seen in Figure 8, the microfluidic chip 210 includes an elongated body 212 having an upper surface 213 and a lower surface 214. The upper surface 213 and the lower surface 214 extend longitudinally from a first end 215 to a second end 216, and extend laterally from a first lateral side 217 to a second lateral side 218.

[0093] As seen in Figure 9. the body 212 can be formed of various layers. In the illustrated embodiment, the microfluidic chip 210 is generally formed by one or more of a first (lower) layer 221, a second (intermediate / lower) layer 222, a third (intermediate) layer 223, a fourth (intermediate / upper) layer 224, a fifth (upper) layer 225, a sixth (intermediate / upper) layer 226 and a seventh (upper) layer 227. As with the microfluidic chip 10, the terms “first / ’ “second,” “third,” etc. can be used interchangeably, and layers can be combined or further separated.

[0094] In the illustrated embodiment, the first layer 221 is a transparent layer which forms the lower surface 214 of the body 212. The transparent first layer 221 enables a user to view through the lower surface 214 into the microchannels 230, 232, 234, the viewing area 236 and the inner area 256 of the output silo 252. In an embodiment, the first layer 221 is formed of 0.25 mm thick transparent acrylic film.

[0095] In the illustrated embodiment, the second layer 222 is an adhesive layer which adheres the first layer 221 to the third layer 223. In an embodiment, the second layer 222 is formed of double-sided pressure sensitive adhesive (PSA). In another embodiment, the second layer 222 can be formed by applying another type of adhesive between the first layer 221 to the third layer 223.

[0096] In the illustrated embodiment, the third layer 223 is a rigid part forming the majority of the height of the microfluidic chip 210. The third layer 223 also forms the majority of the viewing area 236, the input silo 242 and the output silo 252. In an embodiment, the third layer223 is a 3D printed slide. The third layer 223 can be made of polycarbonate, polypropylene, polymethyl methacrylate, or any plastic material. The third layer 223 can also be formed of other methods besides 3D printing, for example, by injection molding, blow molding, thermoforming, compression molding, transfer molding, CNC machining, casting, or other suitable methods.

[0097] In the illustrated embodiment, the fourth layer 224 is an adhesive layer which adheres the third layer 221 to the fifth layer 225. Similarly, the sixth layer 226 is an adhesive layer which adheres the third layer 221 to the seventh layer 227. In an embodiment, the fourth layer224 and the sixth layer 226 are formed of double-sided pressure-sensitive adhesive (PSA). In another embodiment, the fourth layer 224 and the sixth layer 226 can be formed by applying another type of adhesive between the respective bordering layers.

[0098] In the illustrated embodiment, the fifth layer 225 is a transparent layer which forms part of the upper surface 213 of the body 212. The transparent fifth layer 225 enables a user to view through the upper surface 213 into the output silo 252. In an embodiment, the fifth layer 225 is formed of 0.25 mm thick transparent acrylic film.

[0099] In the illustrated embodiment, the seventh layer 227 is a transparent layer which forms part of the upper surface 213 of the body 212. The transparent seventh layer 227 forms a viewing window for the viewing area 236, enabling a user to view the cells within the viewing area 236 from above. In an embodiment, the seventh layer 227 is formed of 0.25 mm thick transparent acrylic film.

[0100] The microfluidic chip 210 also includes a filter 238. The filter 238 is configured to filter at least some cells input into the microfluidic chip 210 from fluid mixed with the cells as the fluid and cells travel through the microfluidic chip 210, as explained in more detail below. In an embodiment, the filter 238 is formed of an 18-micron filter mesh material.

[0101] The microfluidic chip 210 also includes an air vent cover 239. The air vent cover 239 is attached to the fifth layer 225 by way of an adhesive, or over-molded in place. In an embodiment, the air vent cover 239 is formed of nylon mesh, filter paper, or other common filter material.

[0102] The microfluidic chip 210 includes at least one microchannel 230. In the illustrated embodiment, the at least one microchannel 230 includes a first microchannel 232 and a second microchannel 234. The microfluidic chip 210 also includes a viewing area 236. The viewing area 236 is in fluid communication with the at least one microchannel 230. The viewing area 236 is configured to enable a visual diagnostic of the cells that have flowed through the at least one microchannel 230.

[0103] As seen in Figures 8 to 10, the first microchannel 232 and the second microchannel 234 extend in the longitudinal direction of the body 212. The viewing area 236 is located between the first microchannel 232 and the second microchannel 134 in the longitudinal direction. The first microchannel 232 and the second microchannel 234 are longer than the viewing area 236 in the longitudinal direction. The viewing area 136 is wider than the first microchannel 232 and the second microchannel 234 in the lateral direction. The first microchannel 232 and the second microchannel 134 are each in fluid communication with the viewing area 236. such that fluid with cells can travel through the first microchannel 232 to the viewing area 236 and then from the viewing area 236 through the second microchannel 234.

[0104] In the illustrated embodiment, the first microchannel 232 and the second microchannel 234 are formed as elongated cutouts through the second layer 222. as seen in Figure 9. The first layer 221 forms the lower surfaces of the first microchannel 232 and the second microchannel 234, and the third layer 223 forms the upper surfaces of the first microchannel 232 and the second microchannel 234.

[0105] In the illustrated embodiment, the viewing area 236 includes a cutout 236a in the third layer 223, a cutout 236b in the sixth layer 226, a cutout 236c in the second layer 222. and an upper viewing window formed by the seventh layer 227. As seen in Figure 10, the cutout 236a, the cutout 236b and the cutout 236c form a viewing chamber 236c beneath a viewing window 236d formed by the seventh layer 227. The viewing window 236d is the portion of the seventh layer 227 located directly above the viewing 236c. The first layer 221 forms the lower surface of the viewing chamber 236c. In the illustrated embodiment, the viewing chamber 136c is about 0.75 mm deep.

[0106] The microfluidic chip 210 includes an input area 240. The input area 240 includes a first (or input) silo 242. The first silo 242 is configured to receive cells obtained from a patient so that the cells can undergo the visual diagnostic. The first silo 242 is also configured to receive dyed fluid and / or clear fluid during the method of use discussed in more detail below. The first silo 242 extends upward from the third layer 223 at the first end 215 of the body 212. More specifically, the first silo 242 includes an outer wall 244 that extends outward from the upper surface of the third layer 223. The first silo 242 includes an inner area 246 located within the outer surface 244. The inner area 246 is in fluid communication with the first microchannel 232 at the lower end thereof, as seen in Figure 10. In use, a user (e.g., clinician or interventional radiologist) can place a needle or pipette containing cells from an FNA procedure into the input silo 242 and deposit the cells, as well as dyed fluid and / or clear fluid, so that the cells flow through the first microchannel 232 to the viewing area 236.

[0107] The microfluidic chip 210 also includes an output area 250. The output area 250 is an overflow area and includes a second (or output / overflow) silo 252. The second silo 252 is configured to permit an overflow of the fluid input at the input silo 242. The second silo 252 extends upward from the third layer 223 at the second end 216 of the body 212. More specifically , the second silo 252 includes an outer surface 254 that extends outward from the upper surface of the third layer 223. The output silo 252 includes an inner area 256 located within the outer surface 254. The inner area 256 is in fluid communication with the second microchannel 234 and receives the overflow fluid during the method of use discussed below. As seen in Figure 10, fluid enters the inner area 256 at an entry point 255 that is located at or near the upper part of the output surface 254, and vertically above each of the first microchannel 232, the second microchannel 234 and the viewing area 236. which causes the fluid that fills the inner area 256 during the method of use discussed below to remain in the inner area 256 when the cells are withdrawn from the input area 240 at the end of the method.

[0108] As seen in Figures 9 and 10, the output surface 254 surrounding the output area 256 further forms an outlet microchannel 257 and an air vent 258. The outlet channel 257 includes a vertically extending microchannel 259 and a longitudinally extending microchannel 260. The at least one microchannel 230 thus includes the vertically extending microchannel 259 and the laterally extending microchannel 260. The vertically extending microchannel 259 extends vertically through the output surface 254 and fluidly connects the second microchannel 234 and the longitudinally extending microchannel 260. The longitudinally extending microchannel 260 fluidly connects the vertically extending microchannel 259 and the inner area 256 of the output silo 252. In an embodiment, the vertically extending microchannel 259 and / or the longitudinally extending microchannel 260 can be angled instead of extending straight vertically or laterally, or can be combined or further separated into additional microchannels.

[0109] In the illustrated embodiment, the inner area 256 is formed by a cutout 256a in the second layer 222, a cutout 256b in the third layer 223 and a cutout 256c in the fourth layer 224, as seen in Figure 9. The first layer 221 forms the bottom surface of the inner area 256 and the fifth layer 225 forms the upper surface of the inner area 256. Since the fifth layer 225 is transparent, the fifth layer 225 also creates a viewing window allowing a user to view the fluid within the inner area 256 of the output silo 252.

[0110] In the illustrated embodiment, the vertically extending microchannel 259 is formed by a cutout through the height of the third layer 223, while the longitudinally extending microchannel 260 is formed by a cutout 260a in the upper surface of the third layer 223 and acutout 260b through the fourth layer 224. The third layer 223 forms the bottom surface of the longitudinally extending microchannel 260 and the fifth layer 225 forms the upper surface of the vertically extending microchannel 259 and the longitudinally extending microchannel 260. [OHl] In the illustrated embodiment, the filter 238 is located along the outlet microchannel 257. More specifically, the filter 238 is located where the longitudinally extending microchannel 260 meets the vertically extending microchannel 259. This way, the filter 238 prevents at least some of the cells traveling with fluid through the vertically extending microchannel 259 from continuing through the longitudinally extending microchannel 260 and into the inner area 256 of the output silo 252. Thus, the filter 238 prevents at least some of the cells from traveling through the outlet microchannel 257 into the inner area 256 at the entry point 255.

[0112] In the illustrated embodiment, the air vent 258 is formed by a cutout 261 in the fifth layer 225 and the air vent cover 239. Here, the cutout 261 forming the air vent 258 is located directly above the inner area 256 of the output silo 252. The air vent cover 239 is attached over the cutout 261 as to permit air to escape the inner area 256 through the air vent 258.

[0113] Figures 1 1 to 13 illustrate a fourth example embodiment of a microfluidic chip 310 which locates the filter 338 within a chamber 337 adjacent to and downstream of the viewing area 336. As seen in Figure 11, the microfluidic chip 310 includes an elongated body 312 having an upper surface 313 and a lower surface 314. The upper surface 313 and the lower surface 314 extend longitudinally from a first end 315 to a second end 316, and extend laterally from a first lateral side 317 to a second lateral side 318.

[0114] As seen in Figure 12, the body 312 can be formed of various layers. In the illustrated embodiment, the microfluidic chip 310 is generally formed by one or more of a first (lower) layer 321, a second (intermediate / lower) layer 322. a third (intermediate) layer 323, a fourth (intermediate / upper) layer 324, a fifth (upper) layer 325, a sixth (intermediate / upper) layer 326, a seventh (upper) layer 327, an eighth (intermediate / upper) layer 328 and a ninth (upper) layer 329. As with the microfluidic chips 10, 110, 210 the terms “first,” “second,” “third,” etc. can be used interchangeably, and layers can be combined or further separated.

[0115] In the illustrated embodiment, the first layer 321 is a transparent layer which forms the lower surface 314 of the body 312. The transparent first layer 321 enables a user to view through the lower surface 314 into the microchannels 330, 332, 334, the viewing area 336 and the inner area 356 of the output silo 352. In an embodiment, the first layer 321 is formed of 0.25 mm thick transparent acrylic film.

[0116] In the illustrated embodiment, the second layer 322 is an adhesive layer which adheres the first layer 321 to the third layer 323. In an embodiment, the second layer 322 is formed of double-sided pressure sensitive adhesive (PSA). In another embodiment, the second layer 322 can be formed by applying another type of adhesive between the first layer 321 to the third layer 323.

[0117] In the illustrated embodiment, the third layer 323 is a rigid part forming the majority’ of the height of the microfluidic chip 310. The third layer 323 also forms the majority of the viewing area 336, the input silo 342 and the output silo 352. In an embodiment, the third layer 323 is a 3D printed slide. The third layer 323 can be made of polycarbonate, polypropylene, polymethyl methacry late, or any plastic material. The third layer 323 can also be formed of other methods besides 3D printing, for example, by injection molding or other suitable methods blow molding, thermoforming, compression molding, transfer molding, CNC machining, casting,

[0118] In the illustrated embodiment, the fourth layer 324 is an adhesive layer which adheres the third layer 321 to the fifth layer 325. Similarly, the sixth layer 326 is an adhesive layer which adheres the third layer 321 to the seventh layer 327. and the eighth layer 328 is an adhesive layer which adheres the third layer 321 to the ninth layer 329. In an embodiment, the fourth layer 324, the sixth layer 326 and the eighth layer 328 are formed of double-sided PSA. In another embodiment, the fourth layer 324, the sixth layer 326 and the eighth layer 328 can be formed by applying another type of adhesive between the respective bordering layers.

[0119] In the illustrated embodiment, the fifth layer 325 is a transparent layer which forms part of the upper surface 313 of the body 312. The transparent fifth layer 325 enables a user to view through the upper surface 313 into the output silo 352. In an embodiment, the fifth layer 325 is formed of 0.25 mm thick transparent acrylic film.

[0120] In the illustrated embodiment, the seventh layer 327 is a transparent layer which forms part of the upper surface 313 of the body 312. The transparent seventh layer 327 forms a viewing window above the viewing area 336, enabling a user to view into viewing area 336 from above. In an embodiment, the seventh layer 327 is formed of 0.25 mm thick transparent acrylic film.

[0121] In the illustrated embodiment, the ninth layer 329 is a transparent layer which forms part of the upper surface 313 of the body 312. The transparent ninth layer 329 enables a user to view through the upper surface 313 into the filter chamber 337. In an embodiment, the ninth layer 329 is formed of 0.25 mm thick transparent acrylic film.

[0122] The microfluidic chip 310 also includes a filter 338. The filter 338 is configured to filter at least some cells input into the microfluidic chip 310 from fluid mixed with the cells as the fluid and cells travel through the microfluidic chip 310, as explained in more detail below. In an embodiment, the filter 338 is formed of an 18-micron filter mesh material.

[0123] The microfluidic chip 310 also includes an air vent cover 339. The air vent cover 339 is attached to the fifth layer 325 via an adhesive, or overmolded in place. In an embodiment, the air vent cover 339 is formed of nylon mesh, filter paper, or other common filter material.

[0124] The microfluidic chip 310 includes at least one microchannel 330. In the illustrated embodiment, the at least one microchannel 330 includes a first microchannel 332, a second microchannel 334 and a third microchannel 335. The microfluidic chip 310 also includes a viewing area 336 and a filter chamber 337. The viewing area 336 and the filter chamber 337 are in fluid communication with the at least one microchannel 330. The viewing area 336 is configured to enable a visual diagnostic of the cells that have flowed through the at least one microchannel 330. The filter chamber 337 is configured to filter at least some cells input into the microfluidic chip 310 from fluid mixed with the cells as the fluid and cells travel downstream from the viewing area 336.

[0125] As seen in Figures 11 to 13, the first microchannel 332, the second microchannel 334 and the third microchannel 335 extend in the longitudinal direction of the body 312. The viewing area 336 is located between the first microchannel 332 and the third microchannel 334 in the longitudinal direction. The filter chamber 337 is located between the second microchannel 334 and the third microchannel 334 in the longitudinal direction. The first microchannel 332, the second microchannel 334 and the third microchannel 335 are each in fluid communication with the viewing area 236 and the filter chamber 337, such that fluid with cells can travel through the first microchannel 332 to the viewing area 336, from the viewing area 336 to the third microchannel 335, from the third microchannel 335 to the filter chamber 337, and then from the filter chamber 337 through the second microchannel 334.

[0126] In the illustrated embodiment, the first microchannel 332 includes a first portion 332a and a second portion 332b. As seen in Figure 13, the second portion 332b is located vertically higher than the first portion 332a. As seen in Figure 12, the second layer 322 forms the first portion 332a, and the third layer 323 forms the second portion 332b. More specifically, the first portion 332a is formed as an elongated cutout through the second layer 322, and the second portion 332b is formed as an elongated cutout into the upper surface of the third layer 323. The first layer 321 forms the lower surface of the first portion 332a, and the third layer 323 forms the upper surface of the first portion 332a. The third layer 323 forms the lower surface of thesecond portion 332b. and the sixth layer 326 or the seventh layer 327 forms the upper surface of the second portion 332b. In the illustrated embodiment, the sixth layer 326 includes a cutout 332c forming part of the second portion 332b, and the seventh layer 327 enables a user to see into the second portion 332b from above.

[0127] In the illustrated embodiment, the second microchannel 334 includes a first portion 334a and a second portion 334b. As seen in Figure 13, the first portion 334a is located vertically higher than the second portion 334b. As seen in Figure 12. the second layer 322 forms the second portion 334b, and the third layer 323 forms the first portion 334a. More specifically, the second portion 334b is formed as an elongated cutout through the second layer 322, and the first portion 334a is formed as an elongated cutout into the upper surface of the third layer 323. The first layer 321 forms the lower surface of the second portion 334b, and the third layer 323 forms the upper surface of the second portion 334b. The third layer 323 forms the lower surface of the first portion 334a, and the eighth layer 328 or the ninth layer 329 forms the upper surface of the first portion 334a. In the illustrated embodiment, the eighth layer 328 includes a cutout 334c forming part of the first portion 334a, and the ninth layer 329 enables a user to see into the first portion 334a from above.

[0128] In the illustrated embodiment, the viewing area 336 includes a cutout 336a in the third layer 323, a cutout 336b in the sixth layer 326, a cutout 336c in the second layer 322, and an upper viewing window formed by the seventh layer 327. As seen in Figure 13, the cutout 336a, the cutout 336b and the cutout 336c form a viewing chamber 336c beneath a viewing window 336d formed by the seventh layer 327. The viewing window 336d is the portion of the seventh layer 327 located directly above the viewing chamber 336c. The first layer 321 forms the lower surface of the viewing chamber 336c. In the illustrated embodiment, the viewing chamber 336c is about 0.75 mm deep.

[0129] In the illustrated embodiment, the filter chamber 337 is formed by a cutout 337a in the second layer 322 and a cutout 337b in the third layer 323, which are located on opposite sides of the filter 338 as seen in Figure 12. That is, the filter 338 is located within the filter chamber 337. The first layer 321 forms the lower surface of the filter chamber 337, and the eighth layer 328 or the ninth layer 329 forms the upper surface of the filter chamber 337. In the illustrated embodiment, the eighth layer 328 includes a cutout 337c forming part of the filter chamber 337, and the ninth layer 329 enables a user to see into the filter chamber 337 from above.

[0130] The microfl ui die chip 310 includes an input area 340. The input area 340 includes a first (or input) silo 342. The first silo 342 is configured to receive cells obtained from a patient so that the cells can undergo the visual diagnostic. The first silo 342 is also configured toreceive dyed fluid and / or clear fluid during the method of use discussed in more detail below. The first silo 342 extends upward from the third layer 323 at the first end 318 of the body 312. More specifically, the first silo 342 includes an outer wall 344 that extends outward from the upper surface of the third layer 323. The first silo 342 includes an inner area 346 located within the outer surface 344. The inner area 346 is in fluid communication with the first microchannel 332 at the lower end thereof, as seen in Figure 13. In use, a user (e.g., clinician or interventional radiologist) can place a needle or pipette containing cells from an FNA procedure into the input silo 342 and deposit the cells, as well as dyed fluid and / or clear fluid, so that the cells flow through the first microchannel 332 to the viewing area 336.

[0131] The microfluidic chip 310 also includes an output area 350. The output area 350 is an overflow area and includes a second (or output / overflow) silo 352. The second silo 352 is configured to permit an overflow of the fluid input at the input silo 342. The second silo 352 extends upward from the third layer 323 at the second end 316 of the body 312. More specifically, the second silo 352 includes an outer surface 354 that extends outward from the upper surface of the third layer 323. The output silo 352 includes an inner area 356 located within the outer surface 354. The inner area 356 is in fluid communication with the second microchannel 334 and receives the overflow fluid during the method of use discussed below. As seen in Figure 13, fluid enters the inner area 356 at an entry’ point 355 that is located at or near the upper part of the output surface 354, and vertically above each of the first microchannel 332, the second microchannel 334 and the viewing area 336. which causes the fluid that fills the inner area 356 during the method of use discussed below to remain in the inner area 356 when the cells are withdrawn from the input area 340 at the end of the method.

[0132] As seen in Figures 12 and 13, the output surface 354 surrounding the output area 356 further forms an outlet microchannel 357 and an air vent 358. The outlet channel 357 includes a vertically extending microchannel 359 and a longitudinally extending microchannel 360. The at least one microchannel 330 thus includes the vertically extending microchannel 359 and the laterally extending microchannel 360. The vertically extending microchannel 359 extends vertically through the output surface 354 and fluidly connects the second microchannel 334 and the longitudinally extending microchannel 360. The longitudinally extending microchannel 360 fluidly connects the vertically extending microchannel 359 and the inner area 356 of the output silo 352. In an embodiment, the vertically extending microchannel 359 and / or the longitudinally extending microchannel 360 can be angled instead of extending straight vertically or laterally, or can be combined or further separated into additional microchannels.

[0133] In the illustrated embodiment, the inner area 356 is formed by a cutout 356a in the second layer 322, a cutout 356b in the third layer 323 and a cutout 356c in the fourth layer 324, as seen in Figure 12. The first layer 321 forms the bottom surface of the inner area 356 and the fifth layer 325 forms the upper surface of the inner area 356. Since the fifth layer 325 is transparent, the fifth layer 325 also creates a viewing window allowing a user to view the fluid within the inner area 356 of the output silo 352.

[0134] In the illustrated embodiment, the vertically extending microchannel 359 is formed by a cutout through the height of the third layer 323, while the longitudinally extending microchannel 360 is formed by a cutout 360a in the upper surface of the third layer 323 and a cutout 360b through the fourth layer 324. The third layer 323 forms the bottom surface of the longitudinally extending microchannel 360 and the fifth layer 325 forms the upper surface of the vertically extending microchannel 359 and the longitudinally extending microchannel 360.

[0135] In the illustrated embodiment, the air vent channel 358 is formed by a vent channel 361 and the vent cover 339. The vent channel 361 is formed by a cutout 361a in the upper surface of the third layer 323, a cutout 361b through the fourth layer 324. and a smaller cutout 361c through the fifth layer 325. The third layer 323 forms the bottom surface of the vent channel 361 and the fifth layer 325 forms the upper surface of the vent channel 361 except at the cutout 361c. The air vent cover 339 is attached over the cutout 361c of the vent channel 361 so as to permit air to escape the inner area 356 through the air vent 358.

[0136] Figure 14 illustrates an example embodiment of a method Ml of using the microfluidic chips 10, 1 10, 210, 310 in accordance with the present disclosure. In an embodiment, the method Ml is a method of preparing, routing and recovering cells for both a visual diagnostic and a molecular diagnostic. Those of ordinary skill in the art will recognize from this disclosure that certain steps of the method Ml can be added, removed or altered without departing from the spirit and scope of the present disclosure. Those of ordinary skill in the art will also recognize from this disclosure that certain steps of the method Ml can be used with other microfluidic chips besides those disclosed herein.

[0137] At step Sl-1. a fine needle aspiration (FNA) procedure is performed to extract cells from a patient. The FNA procedure can be performed using a specifically designed needle that is placed by an interventional radiologist into a suspected tumor mass in an organ, such as the liver, breast, lung, kidney, etc.

[0138] At step Sl-2, the user adds the cells to the input area 40, 140, 240, 340 of the microfluidic chip 10, 110, 210, 310. In an embodiment, the user adds the cells into the inputsilo 42, 142, 242, 342 using a needle or pipete. In an embodiment, the needle can be the needle used to perform the FNA procedure.

[0139] At step SI -3, the user adds a dye fluid to the input area 40, 140, 240, 340 of the microfluidic chip 10, 110, 210, 340. In the illustrated embodiment, the user adds the dye fluid into the input silo 42, 142, 242, 342 using a needle or pipete. The dye fluid then mixes with the cells in the input area 40, 140, 240, 340 and the combination of the fluid and cells begins to flow through the at least one microchannel 30. 130, 230, 330 and / or viewing area 36. 136. 236, 336. The dye fluid is used darken the membranes of the cells to make them easier to view through the viewing area 36, 136, 236, 336 after clear fluid has driven the dye fluid out of the viewing area, into the output area 50, 150, 250, 350 at step 1-6.

[0140] At step Sl-4. the user applies pressure to the input area 40, 140. 240. The pressure can be applied with a syringe tool T, for example, a plastic syringe. During the method Ml, the syringe has three general functions: (1) push the initial fluid sample taken from the patient into the input area 40, 140, 240, 340, (2) push more fluid (non-dyed) to rinse away the dye after the cells have been dyed, and (3) pull the cells back out of the input area 40, 140, 240, 340 to recover them for molecular testing.

[0141] Figure 15 A illustrates an example embodiment of step Sl-4 being performed on the microfluidic chip 10. Here, the user places a syringe tool T over the input area 40 and applies pressure that drives the cells and dyed fluid to at least the viewing area 36. Referring to Figure 4, the cells and dyed fluid are driven through the first portion 32a of the first microchannel 32 and the second portion 32b of the first microchannel 32 and into the viewing area 36. The user can then view the cells within the viewing area 36 using a microscope. The filter 238 prevents at least some of the cells from passing into the lower chamber 37 while allowing the dyed fluid to pass into the lower chamber 37. Excess dyed fluid can then be driven from the lower chamber 37, through the second microchannel 32, through the vertically extending microchannel 59 and the longitudinally extending microchannel 60, and into the inner area 56 if the outlet silo 52. The air vent 39 further allows air to escape the inner area 56 as dyed fluid flow s in. The same general process is followed for the microfluidic chip 110.

[0142] Figure 16A illustrates an example embodiment of step Sl-4 being performed on the microfluidic chip 210. Here, the user places a syringe tool T over the input area 240 and applies pressure that drives the cells and dyed fluid to at least the viewing area 236. Referring to Figure 10, the cells and dyed fluid are driven through the first microchannel 232 and into the viewing area 236. The user can then view the cells within the viewing area 236 using a microscope. The cells and dyed fluid can further be driven from the viewing area 236 through the secondmicrochannel 234 and the vertically extending microchannel 259, until the filter 238 prevents at least some of the cells from passing into the longitudinally extending microchannel 260 while allowing the dyed fluid to pass into longitudinally extending microchannel 260 and then the inner area 256 if the outlet silo 252. The air vent 239 further allows air to escape the inner area 256 as dyed fluid flows in.

[0143] Figure 17A illustrates an example embodiment of step SI -4 being performed on the microfluidic chip 310. Here, the user places a syringe tool T over the input area 340 and applies pressure that drives the cells and dyed fluid to at least the viewing area 336. Referring to Figure 13, the cells and dyed fluid are driven through the first portion 332a of the first microchannel 332 and the second portion 332b of the first microchannel 332 and into the viewing area 336. The user can then view the cells within the viewing area 336 using a microscope. The cells and dyed fluid can further be driven from the viewing area 336 through the third microchannel 335 and into the filter chamber 337, where the filter 338 prevents at least some of the cells from passing into the second microchannel 332, while allowing the dyed fluid to pass into the first portion 334a of the second microchannel 334, the second portion 334b of the second microchannel 334. the vertically extending microchannel 339, the longitudinally extending microchannel 360, and then the inner area 356 if the outlet silo 352. The air vent 339 further allows air to escape the inner area 356 as dyed fluid flows in.

[0144] At step Sl-5, the user adds clear fluid to the input area 40, 140, 240, 340 of the microfluidic chip 10. 110, 210, 310. In the illustrated embodiment, the user adds the clear fluid into the input silo 42, 142, 242, 342 using a needle or pipette. The purpose of the clear fluid is to drive the dyed fluid into the output area 50, 150, 250, 350 so that the user can view' the cells with dyed membranes, but without the surrounding dye fluid, within the viewing area 36, 136, 236, 336.

[0145] At step S 1-6, the user again applies pressure to the input area 40, 140, 240. The pressure can be applied with a syringe tool T such as a common plastic lure-lock syringe with an internal plunger.

[0146] Figure 15B illustrates an example embodiment of step SI -6 being performed on the microfluidic chip 10. Here, the user again places a syringe tool T over the input area 40 and applies pressure that drives the clear fluid along the same path taken by the dyed fluid at step SI -4. The clear fluid drives the dyed fluid out of the viewing area 36. More specifically, the clear fluid drives the dyed fluid from the lower chamber 37, through the second microchannel 32, through the vertically extending microchannel 59 and the longitudinally extending microchannel 60, and into the inner area 56 if the outlet silo 52. The air vent 39 further allowsair to escape the inner area 56 as dyed fluid flows in. As seen in Figure 16B, the viewing area 36 is then full of clear fluid, while the inner area 56 of the output silo 52 includes most or all of the dyed fluid. The same general process is followed for the microfluidic chip 110.

[0147] Figure 16B illustrates an example embodiment of step SI -6 being performed on the microfluidic chip 210. Here, the user again places a syringe tool T over the input area 240 and applies pressure that drives the clear fluid along the same path taken by the dyed fluid at step SI -4. The clear fluid drives the dyed fluid out of the viewing area 236. More specifically, the clear fluid drives the dyed fluid from the viewing area 236 through the second microchannel 234, the vertically extending microchannel 259 and the longitudinally extending microchannel 260, and into the inner area 256 if the outlet silo 252. The air vent 239 further allows air to escape the inner area 256 as dyed fluid flows in. As seen in Figure 16B, the viewing area 236 is then full of clear fluid, while the inner area 256 of the output silo 252 includes most or all of the dyed fluid.

[0148] Figure 17B illustrates an example embodiment of step SI -6 being performed on the microfluidic chip 310. Here, the user again places a syringe tool T over the input area 340 and applies pressure that drives the clear fluid along the same path taken by the dyed fluid at step SI -4. The clear fluid drives the dyed fluid out of the viewing area 336. More specifically, the clear fluid drives the dyed fluid from the viewing area 336 through the third microchannel 335 and into the filter chamber 337, then through the first portion 334a of the second microchannel 334, the second portion 334b of the second microchannel 334, the vertically extending microchannel 339, the longitudinally extending microchannel 360, and then into the inner area 356 if the outlet silo 352. The air vent 339 further allows air to escape the inner area 356 as dyed fluid flows in. As seen in Figure 17B, the viewing area 336 and the filter chamber 337 are then full of clear fluid, while the inner area 356 of the output silo 352 includes most or all of the dyed fluid.

[0149] At step Sl-7, the user views the cells with dyed membranes in the viewing area 36, 136, 236, 336 after the dye fluid has been driven out of the viewing area 36, 136, 236, 336 by the clear fluid. That is, the user views the cells through the viewing window 36d, 136d, 236d, 336d formed by the transparent seventh layer 27, 127. 227, 337 while the cells are located in the viewing chamber 36c, 136c, 236c, 336c beneath the viewing window 36d, 136d, 236d, 336d.

[0150] At step S 1-8, the user then a needle (e.g., syringe) or pipette back into the input area 40, 140, 240. 340 of the microfluidic chip 10. 110, 210, 310. The user can then use the needle or pipette to withdraw the cells and clear fluid from the microfluidic chip 10, 110, 210, 310. The cells and fluid are withdrawn in the opposite flow direction of step SI -4. Since the dyed fluidis now trapped in the output silo 52, 152, 252, 352, the dyed fluid is not withdrawn with the cells and the clear fluid.

[0151] Figures 18A to 18L illustrate example embodiments of the viewing window' 36, 136, 236, 336 under a microscope.

[0152] Figures 18A to 18F show7examples with the filter 38, 138 located directly under the viewing window. Figure 18A shows the mesh clogged with “cells” (simulated by using glass spheres that are approximately the size of clumps of tumor cells) during the method of use discussed above. Figure 18B shows the filter 38, 138 prior to cells being added to the input area 40, 140. Figures 18C and 18E shows the filter 38, 138 trapping the “cells” during the method of use discussed above. Figures 18D and 18F shows step Sl-8 after the cells (glass spheres) have been retracted back to the input area 40, 140.

[0153] Figures 18G to 18L show examples with the filter 338 located directly downstream of the viewing window7336 in the filter cavity 337. Figure 18G shows the viewing cavity 336 prior to cells being added to the input area 340. Figure 18H shows the filter cavity7337 prior to cells being added to the input area 340. Figure 181 shows the viewing cavity 336 displaying the “cells” (simulated by using glass spheres that are approximately the size of clumps of tumor cells) during the method of use discussed above. Figure 18J shows the filter cavity 337 trapping the cells during the method of use discussed above. Figure 18K shows the viewing area 136 after that the “cells” (glass spheres) have been retracted back to the input area 340. Figure 18L shows the filter cavity 337 after that the “cells” (glass spheres) have been retracted back to the input area 340. Figures 19 to 23 illustrate an example embodiment of a microfluidic chip 410 enabling cells to undergo both a visual diagnostic and a molecular diagnostic in accordance with the present disclosure. The microfluidic chip 410 is configured to maximize the clinical benefits of limited amounts of cellular material obtained by a FNA procedure or “touch prep” following a CNB procedure. In use, the microfluidic chip 410 enables cells attached to magnetic beads to move through a microchannel, stop at a certain point, be examined by a microscope (or digitally scanned), then move to the end of the microfluidic chip 10 and be captured for molecular testing.

[0154] As seen in Figures 19 to 23, the microfluidic chip 410 includes an elongated body 412 having an upper surface 414 and a low'er surface 416. The upper surface 414 and the lower surface 416 extend longitudinally from a first end 418 to a second end 420, and extend laterally from a first lateral side 422 to a second lateral side 424. The body 412 can be formed, for example, of glass, silicon or polymer. In an embodiment, the body 412 is formed by a first (or upper) body 426 and a second (or lower) body 428 which are attached together to form thebody 412 such that the first body 426 forms the upper surface 414 and the second body 428 forms the lower surface 416. Alternatively, the body 412 can be formed from a single piece of material (e.g., a single piece of glass, silicon or polymer). In the illustrated embodiment, the body 412 is approximately the size of a standard glass slide for a microscope. As discussed in more detail below, the body 412 is adjustable from a first orientation 01 (shown in Figures 19 to 21) to a second orientation 02 (shown in Figure 22).

[0155] The microfluidic chip 410 includes at least one microchannel 430. In the illustrated embodiment, the at least one microchannel 430 includes a first microchannel 432 and a second microchannel 434. The microfluidic chip 410 also includes a viewing area 436. The viewing area 436 is in fluid communication with the at least one microchannel 430. As discussed in more detail below, the viewing area 436 is configured to enable a visual diagnostic of the cells that have flowed through the at least one microchannel 430. As seen in Figures 19 and 20, the first microchannel 432 and the second microchannel 434 extend in the longitudinal direction of the body 412. The viewing area 436 is located between the first microchannel 432 and the second microchannel 434 in the longitudinal direction. The first microchannel 432 and the second microchannel 434 are longer than the viewing area 436 in the longitudinal direction. The viewing area 436 is wider than the first microchannel 432 and the second microchannel 434 in the lateral direction. The first microchannel 432 and the second microchannel 434 are each in fluid communication with the viewing area 436, such that fluid with cells can travel through the first microchannel 432 to the viewing area 436, and then travel from the viewing area 436 through the second microchannel 434.

[0156] The at least one microchannel 430 can be embedded, etched or molded into the body 412. In an embodiment, the at least one microchannel 430 is embedded, etched or molded into the upper surface 414 of the body 412. In an embodiment, the at least one microchannel 430 is embedded, etched or molded into the first body 426 or the second body 428 before the first body 426 is attached to the second body 428. In an embodiment, the at least one microchannel 430 is positioned within the body 412 between the first surface 414 and the second surface 416. In an embodiment, the at least one microchannel 430 is formed between the first body 426 and the second body 428 when the first body 426 and the second body 428 are attached together in a leak tight manner.

[0157] As seen in Figure 19 and 20, the microfluidic chip 410 includes an input area 440. The input area 440 includes a first (or input) silo 442. The first silo 442 is configured to receive cells obtained from a patient so that the cells can undergo the visual diagnostic. The first silo 442 extends from the upper surface 414 at the first end 418 of the body 412. More specifically,the first silo 442 includes an outer wall 444 that extends outward from the upper surface 414 of the body 412. The input silo 442 includes an inner area 446 located within the outer surface 444. The inner area 446 is in fluid communication with the first microchannel 432. In use, a user (e.g., clinician or interventional radiologist) can place a needle or pipette containing cells from an FNA procedure into the input silo 442 and deposit the cells, so that the cells can flow through the first microchannel 432 to the viewing area 436. More specifically, the user can deposit fluid with immunomagnetically bound cells into the input silo 442.

[0158] As seen in Figure 21, the microfluidic chip 410 includes an output area 450. The output area 450 includes a second (or output) silo 452. The second silo 452 is configured to output the cells received at the input silo 442 so that the cells can undergo the molecular diagnostic. The second silo 452 is configured to extend from the lower surface 416 at the second end 420 of the body 412. More specifically, the second silo 452 includes an outer surface 454 that is configured to extend outward from the lower surface 416 of the body 412. The output silo 452 includes an inner area 456 located within the outer surface 454. The inner area 456 is in fluid communication with the second microchannel 434. In use, fluid containing cells from an FNA procedure can flow from the viewing area 436 through the second microchannel 432 to the output silo 452 to be collected for a molecular diagnostic. In the orientation shown in Figure 21, the output silo 452 is in a downward position, which enables cells and fluid to flow7through microchannel(s) 430, 432. 434 to the output silo 452 via capillary action. The at least one microchannel 430 places the first silo 442 and the second silo 452 in fluid communication, such that the cells can flow from the first silo 442, through the at least one microchannel 430, to the second silo 452 to be output for a molecular diagnostic.

[0159] In the illustrated embodiment, the microfluidic chip 410 includes a first (or inlet) part 460 and a second (or outlet) part 462. The first part 460 includes the input area 450, and the second part 462 includes the output area 450. In Figures 21 and 22, a boundary line 456 marks the location where the second part 462 is configured to separate and / or move with respect to the first part 460. By separating and / or moving the second part 462 with respect to the first part 460, the microfluidic chip 410 can change between a first (or downward) orientation 01 and a second (or upward) orientation 02. Figures 20 and 21 illustrate the microfluidic chip 410 in the first (downward) orientation 01, Figure 22 illustrates the microfluidic chip 410 in the second (upward) orientation 02, and Figure 23 illustrates how7the second part 462 can separate from and / or move with respect to the first part 460 so that the microfluidic chip 410 changes between the first and second orientations 01, 02. As illustrated, the second part 462 is configured to move with respect to the first part 460 so that the output silo 452 extends fromthe upper surface 414 in a same direction as the input silo 442. In an embodiment, the second part 462 separates partially but not completely from the first part 460 when the microfluidic chip 410 changes from the first orientation 01 to the second orientation 02, or vice versa.

[0160] As seen in Figures 20 and 21, when the microfluidic chip 410 is in the first orientation 01, the first silo 442 projects upward from the upper surface 414, and the second silo 452 projects downward from the lower surface 416. Thus, the input silo 442 and the output silo 452 extend from the body 412 in opposite directions in the first orientation 01. In this orientation, a first surface 415a of the second part 462 is part of the upper surface 414, and a second surface 415b of the second part 462 is part of the lower surface 416. As seen in Figure 21, the second silo 452 extends outward from the second side 415b of the second part 462.

[0161] As seen in Figure 22, when the microfluidic chip 410 is in the second orientation 02, both the first silo 442 and the second silo 452 project upward from the upper surface 414. Thus, the input silo 442 and the output silo 452 extend from the body 412 in a same direction in the second orientation 02. In this orientation, the first surface 415a of the second part 462 becomes part of the lower surface 416, and the second surface 415b of the second part 462 becomes part of the upper surface 414. To change to the second orientation 02, as seen in Figure 23. the second part 462 rotates and / or flips to change the vertical orientation of the second silo 352 between the first (downw ard) orientation 01 and the second (upw ard) orientation 02.

[0162] When the second (output) silo 452 is in the first (downward) orientation 01, the microfluidic chip 410 allows cells to flow through the first microchannel 432 until they reach the central widened viewing area 436. With the second silo 452 in the first orientation 01 , gravity causes fluid to flow along the pathway of the first microchannel 432 and through the cells therein via capillary action. Each drop of fluid that leaves the microfluidic chip 410 pulls another drop of fluid volume to take its place, hence the movement of fluid. By contrast, when the second silo 452 in the second (upward) orientation 02, the fluid remains stationary, so cells will remain in central viewing area 436 while on a microscope stage or scanning micrograph area. When the user translates a magnet to be positioned directly underneath the widened viewing central area 436 as discussed herein, as the fluid and immunomagnetically bound cells pass over the magnet, the bound cells thereby become stationary.

[0163] As seen in Figures 21 and 22, in an embodiment, the second part 462 includes a partial microchannel 468 that is placed in fluid communication with the at least one microchannel 430 when the second part 462 moves so that the output silo 452 extends from the upper surface 414 in the same direction as the input silo 442. More specifically, the second part 462 includes a partial microchannel 468 that is placed in fluid communication with the first microchannel 432,the second microchannel 434 and / or the viewing area 436 when the microfluidic chip 4310 is in the second orientation 02 (Figure 22).

[0164] In an embodiment, the microfluidic chip 410 can be formed and dimensioned such that either of the first silo 442 or the second silo 452 can be used as an input silo, with the other of the first silo 442 and the second silo 452 being used as an output silo. For example, both the input area 440 and the output area 442 can be made so as to separate and / or move with respect to a central part of the body 412 including the viewing area 436. This embodiment prevents the user from mistakenly pipetting cells and fluid into the wrong silo 442, 452 because either silo 442, 452 can be used as the input silo or output silo.

[0165] In an embodiment, the microfluidic chip 410 can be formed from a plurality of pieces. More specifically, each of the first part 460 and the second part 462 can be formed from a plurality of pieces. As seen in Figure 22, the first part 460 can be formed of a first piece 460a and a second piece 460b. The first piece 460a can include at least part of the at least one microchannel 430 (e.g., in Figure 22, the first microchannel 430 and part of the second microchannel 434), the viewing area 436 and / or the first silo 442. The second piece 460b includes a flat base. The second part 462 can also be formed of a first piece 462a and a second piece 462b. The first piece 462a can include at least part of the at least one microchannel 430 (e.g., in Figure 22, part of the second microchannel 434) and / or the second silo 452. The second piece 460b includes a flat base. The first part 460 can be formed by attaching the first piece 460a to the second piece 460b, and the second part 462 can be formed by attaching the first piece 462a to the second piece 462b. In an embodiment, the first piece 460a attaches to the second piece 460b using a snap-fit, and the first piece 462a attaches to the second piece 462b using a snap-fit. In an embodiment, the at least one microchannel 430 (including the first microchannel 432 and / or the second microchannel 434) and / or the viewing area 436 can be formed between the first piece 460a and the second piece 460b when the first piece 460a is attached to the second piece 460b. Similarly, part of the at least one microchannel 430 (e.g., another part of the second microchannel 434) can be formed between the first piece 462a and the second piece 462b when the first piece 462a is attached to the second piece 462b.

[0166] Figure 24 illustrates an example embodiment of a microfluidic chip 410’ with a mechanical attachment mechanism 470’ configure to enable the second part 462 including the second silo 442’ to separate from the first part 460’. The microfluidic chip 410’ can include all of the elements of the microfluidic chip 410 illustrated in Figures 19 to 23. In the illustrated embodiment of Figure 24, one of the first part 460’ and the second part 462’ includes a projection 472’ and the other of the first part 460’ and the second part 462’ includes acorresponding groove 474'. An outer part 476' of the projection 472’ forms a key with a unique shape (e.g., here, a diamond), and an inner part 478’ of the groove 474’ has the same unique shape so that the projection 472’ can slide laterally into the groove 474’ with the second part 462’ in either the first orientation 01 or the second orientation 02. Those of ordinary skill in the art will recognize from this disclosure that there are other ways of removably attaching the first part 460, 460’ and the second part 462. 462' that enable adjustment between the first orientation 01 and the second orientation 02.

[0167] Figures 25 and 26 illustrate an example embodiment of a supportive device 500 configured to be used in combination with the microfluidic chip 410. Figure 25 illustrates the supportive device 500 without the microfluidic chip 410 mounted thereon, while Figure 26 illustrates the microfluidic chip 410 mounted on the supportive device 500. As discussed in more detail below, the supportive device 500 enables cells from an FNA procedure to undergo both a visual diagnostic and a molecular diagnostic.

[0168] In the embodiment illustrated in Figures 25 and 26, the supportive device 500 includes a base 502. a microfluidic chip mount 504, an alignment arm 506 and an output container 508. In the illustrated embodiment, the microfluidic chip mount 504. the alignment arm 506 and the output container 508 are attached to each other via the base 502. In an embodiment, the supporting device 500 can be formed by 3D printing or injection molding.

[0169] The microfluidic chip mount 504 is configured to removably receive a microfluidic chip 410 in an orientation in which cells can be deposited at an input area 440 of the microfluidic chip 410 and flow through the microfluidic chip 410 via capillary action. The microfluidic chip mount 504 includes a first side mount 510 and a second side mount 512 configured to hold the microfluidic chip 410 in place while the alignment arm 506 is moved into and out of alignment with the microfluidic chip 410. As seen in Figure 25, the first side mount 510 includes a first indentation 514 configured to receive one end of the microfluidic chip 410, and the second side mount 512 includes a second indentation 516 configured to receive the other side of the microfluid chip 410. Figure 26 illustrates the microfluidic chip 410 mounted with one end in the first indentation 514 and the other end in the second indentation 516.

[0170] The alignment arm 506 is configured to translate a magnetic force into and out of alignment with the microfluidic chip 410. More specifically, the alignment arm 506 includes a magnet 524 and is configured to move with respect to the microfluidic chip mount 504 to translate the magnet 524 into and out of alignment with the viewing area 436 of the microfluidic chip 410 when the microfluidic chip 410 is mounted on the microfluidic chip mount 404. Inthe illustrated embodiment, the alignment arm 506 moves with respect to a stationary part 520 of the base 502. The alignment arm 506 has a first end 522 including the magnet 524 and a second end 526 configured to be gripped by a user. In the illustrated embodiment, the magnet 524 is fitted into an aperture in the first end 522. When the user grips the second end 526 and causes the alignment arm 506 to travel in the first direction DI, the alignment arm 506 translates the magnet 524 into alignment with the viewing area 436 of the microfluidic chip 410. When the user causes the alignment arm 506 to travel in the opposite second direction D2. the alignment arm 506 translates the magnet 524 out of alignment with the viewing area 436 of the microfluidic chip 410. In the illustrated embodiment, the magnet 524 is aligned with the viewing area 436 of the microfluidic chip 410 when it is located vertically below the viewing area 436. Thus, in an embodiment, the alignment arm 506 is configured to translate the magnet 524 vertically beneath the viewing area 436 of the microfluidic chip 410 to place the magnet 524 into alignment with the viewing area 436.

[0171] In the illustrated embodiment, the alignment arm 506 moves linearly in the lateral direction of the microfluidic chip 410. In other embodiments, the alignment arm 506 can move in other ways and / or directions, for example, can be rotated or translated vertically or diagonally with respect to the microfluidic chip 410. In another alternative embodiment, the alignment arm 506 and / or its magnet 524 can remain stationary' and the microfluidic chip mount 504 can move the microfluidic chip 410 into alignment with the magnet 524.

[0172] The output container 508 is positioned vertically beneath the output area 450 of the microfluidic chip 410 when the microfluidic chip 410 is mounted on the microfluidic chip mount 504. More specifically, the output container 508 is positioned vertically beneath the second silo 452 when the microfluidic chip 410 is mounted by the microfluidic chip holder 504 with the second silo in the first (downward) orientation 01. In the illustrated embodiment, the output container 508 includes a fluid collecting area 530 that is located beneath the second silo 452 when the microfluidic chip 410 is mounted by the microfluidic chip holder 504. The fluid collecting area 530 can include a first opening 532 to collect fluid that drips out of the second silo 452 when the second silo 452 is in the first (downward) orientation 01. In an embodiment, the first opening 532 removably receives a container configured to collect the fluid that drips out of the second silo 452 when the second silo 452 is in the first orientation 01. In the illustrated embodiment, the output container 508 also includes a second opening 534 to collect excess fluid as the cells move in the at least one microchannel 430, 432, 434 until aligned with the magnet 524 and ready for viewing. In an embodiment, the second opening 534 removably receives a container configured to collect the fluid that drips out of the second silo 452 whenthe second silo 452 is in the first orientation 01. In an embodiment, the second (larger) opening is used to collect fluid that helps move cells to the viewing area 436. and then the first (smaller) opening is used to collect the cells. In an embodiment, the output container 508 can move with respect to the microfluidic chip holder 504 (or vice versa) such that the output area 530 moves into and out of alignment with the second silo 452. More specifically, the output container 508 can move with respect to the microfluidic chip holder 504 (or vice versa) such that either of the first opening 532 or the second opening 534 can alternatively be located underneath the second silo 452.

[0173] In the illustrated embodiment, the movements of the microfluidic chip 410 and the supportive device 500 are manual. It will be understood by those of ordinary skill in the art from this disclosure that one or more operations of the microfluidic chip 410 and / or the supportive device 500 can be made automatic. For example, in an embodiment, the supportive device 500 can be include one or more motor and / or processor configured to automatically introduce cells into the first silo 442, translate the moving arm 506 into and / or out of alignment with the microfluidic chip 410, translate the output container into and / or out of alignment with the microfluidic chip 410. record images of cells while located in the viewing area 436 of the microfluidic chip 410, and / or move the second part 462 between the first (downward) orientation 01 and the second (upward) orientation 02.

[0174] Figure 27 illustrates an example embodiment of a method M2 of using the microfluidic slide 410 and / or the supportive device 500 in accordance with the present disclosure. In an embodiment, the method M2 is a method of preparing and routing cells for both a visual diagnostic and a molecular diagnostic. Those of ordinary' skill in the art will recognize from this disclosure that certain steps of the method M2 can be added, removed or altered without departing from the spirit and scope of the present disclosure. Those of ordinary’ skill in the art will also recognize from this disclosure that certain steps of the method M2 can be used with other microfluidic chips and / or supportive devices besides those disclosed herein disclosed herein.

[0175] At step S2-1. a fine needle aspiration (FNA) procedure is performed to extract cells from a patient. The FNA procedure can be performed using a specifically designed needle that is placed by an interventional radiologist into a suspected tumor mass in an organ, such as the liver, breast, lung, kidney, etc. The extracted cells can be placed in a container such as a microcentrifuge tube.

[0176] At step S2-2. immunomagnetic beads are added to the extracted cells. The immunomagnetic beads are magnetic beads with an antibody to a cell membrane proteinatached. The immunomagnetic beads can be added to the container (e.g., microcentrifuge tube) already containing the cells. The amount of immunomagnetic beads to add to the container may vary and can be determined though reasonable experimentation.

[0177] At step S2-3, the immunomagnetic beads attach to the extracted cells. More specifically, the extracted cells and immunomagnetic beads are incubated to cause the immunomagnetic beads to attach to the extracted cells. The extracted cells and immunomagnetic beads can be incubated by placing the container (e.g., microcentnfuge tube) containing the extracted cells and immunomagnetic beads into an incubator. The extracted cells and immunomagnetic beads typically only need to be incubated for a few minutes for the immunomagnetic beads to attach to the extracted cells. The incubation time may vary. In one embodiment, the extracted cells and immunomagnetic beads can be incubated for approximately 5 minutes. In another embodiment, they can be incubated for approximately 20 minutes.

[0178] At step S2-4, the extracted cells with immunomagnetic beads attached are stained. In an embodiment, the extracted cells are stained with a supravital stain. One such stain is methylene blue works well, but those of ordinary skill in the art will recognize from this disclosure that other stains can also be used. The extracted cells can be stained while still in the container (e g., microcentrifuge tube).

[0179] At step S2-5, the microfluidic slide 410 is mounted on the supportive device 500. In the embodiment shown in Figures 25 and 26, the microfluidic slide 410 is placed into the supportive device 500 with one end in the first indentation 514 and the other end in the second indentation 51 . Those of ordinary skill in the art will recognize from this disclosure that there are other ways to sufficiently mount the microfluidic slide 410 on the supportive device 500. At this point, the microfluidic slide 410 is in the first (downward) orientation 01.

[0180] At step S2-6. the user adds the stained cells to the input area 440 of the microfluidic chip 410. In the illustrated embodiment, the user pipettes the stained cells with immunomagnetic beads attached into the input silo 442 while the microfluidic slide 410 is mounted on the supportive device 500. The stained cells will move through the first microchannel 432 to the viewing area 436 due to capillary’ action as discussed above. In an embodiment, the user pipettes fluid into the microfluidic chip 410 before pipetting the fluid with the stained cells. This is to ensure that the microchannel 430, 432, 434 is already filled w ith fluid and to prevent the addition of bubbles

[0181] At step S2-7, the magnet 524 is aligned with the view ing area 436 of the microfluidic chip 410. More specifically, the user causes the alignment arm 506 to move the magnet 524 into alignment with the viewing area 436. In the illustrated embodiment, the user causes thealignment arm 506 to move the magnet 424 into alignment with the viewing area 436 by translating the magnet 524 linearly in the lateral direction of the microfluidic chip 410 until the magnet 524 is located vertically beneath the viewing area 436. The magnet 524 serves to align and enrich for the cells of interest (bound to the immunomagnetic beads) when the magnet 524 is located below the viewing area 436. When the magnetic force is aligned with the viewing area 436. the cells attached to the immunomagnetic beads collect in the viewing area 436 to enable a visual diagnostic. The user can cause the magnet 524 to translate in the second direction D2 out of alignment, and the cells are expected to remain in the small viewing area for visual examination.

[0182] At step S2-8, the microfluidic chip 410 can be lifted out of the chip mount 504, and the second part 462 can be moved from the first (downward) orientation 01 to the second (upward) orientation 02 as discussed herein. With the second part 462 and thus the second silo 452 in the second orientation 02, there is no more fluid flow and the microfluidic chip 410 can be placed under a microscope for examination of the cells (or scanning).

[0183] At step S2-9. once the cells are aligned in the viewing area 436, the visual diagnostic can be performed. In the illustrated embodiment, the microfluidic chip 410 can be taken off of the microfluidic chip mount 4504 and viewed under a conventional bright field microscope, and / or images of the cells in the viewing area 436 can be digitized using a scanner. In another embodiment, the supportive device 500 includes a scanner configured to digitize images of the fluid in the viewing area 436 while the magnet 524 is located beneath the viewing area 436. In another embodiment, a visual diagnostic can be performed while the microfluidic chip 410 is mounted on the microfluidic chip mount 504.

[0184] At step S2-10, once the cells have been viewed and characterized, the user can enable the cells attached to the immunomagnetic beads to flow to the output area 450 to be collected for a molecular diagnostic, by moving the second part 462 from the second (upward) orientation 01 back to the first (downward) orientation 02 as discussed herein. The user may then place the microfluidic chip 410 back on the microfluidic chip holder 404, and add saline solution or any other buffer fluid through the input silo 442 so as to initiate movement of the cells through the second microchannel 434 towards the output silo 552. where the cells can be collected for downstream testing like molecular analysis.

[0185] The embodiments described herein provide improved devices and methods for both visual and molecular diagnostics of cells. A key advantage of the method enabled by the microfluidic chips 10. 110, 210, 310, 410 and / or the supportive device 500 is that there is maximal utilization of scarce diagnostic cells for purposes of cytologic diagnosis and molecularevaluation in a time efficient, cost-effective manner. It should be understood that various changes and modifications to the devices and methods described herein will be apparent to those skilled in the art and can be made without diminishing the intended advantages.GENERAL INTERPRETATION OF TERMS

[0186] In understanding the scope of the present invention, the term “‘comprising” and its derivatives, as used herein, are intended to be open-ended terms that specify the presence of the stated features, elements, components, groups, and / or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and / or steps. The foregoing also applies to words having similar meanings such as the terms, “including”, “having” and their derivatives. Also, the terms “part,” “section.” or “element” when used in the singular can have the dual meaning of a single part or a plurality of parts.

[0187] The term “configured” as used herein to describe a component, section or part of a device includes hardware and / or software that is constructed to carry out the desired function.

[0188] While only selected embodiments have been chosen to illustrate the present invention, it will be apparent to those skilled in the art from this disclosure that various changes and modifications can be made herein without departing from the scope of the invention as defined in the appended claims. For example, the size, shape, location or orientation of the various components can be changed as needed and / or desired. Components that are shown directly connected or contacting each other can have intermediate structures disposed between them. The functions of one element can be performed by two, and vice versa. The structures and functions of one embodiment can be adopted in another embodiment. It is not necessary7for all advantages to be present in a particular embodiment at the same time. Every7feature which is unique from the prior art, alone or in combination with other features, also should be considered a separate description of further inventions by the applicant, including the structural and / or functional concepts embodied by' such features. Thus, the foregoing descriptions of the embodiments according to the present invention are provided for illustration only, and not for the purpose of limiting the invention as defined by the appended claims and their equivalents.

Claims

WHAT IS CLAIMED IS:

1. A microfluidic chip enabling cells to undergo both a visual diagnostic and a molecular diagnostic, the microfluidic chip comprising: an input area configured to receive cells obtained from a patient; a viewing area in fluid communication with the input area, the viewing area configured to enable a user to view the cells received at the input area; an output area in fluid communication with the input area and the viewing area such that fluid mixed with the cells can flow from the input area, through the viewing area, to the output area; and a filter located between the viewing area and the output area, the filter configured to allow the fluid mixed with the cells to flow into the output area while preventing at least some of the cells from flowing into the output area.

2. The microfluidic chip of claim 1, wherein the viewing area includes a viewing chamber, and the filter is located below the viewing chamber.

3. The microfluidic chip of claim 1, comprising at least one microchannel placing the viewing area and the output area in fluid communication, the filter located along the at least one microchannel dow nstream of the viewing area.

4. The microfluidic chip of claim 3, wherein the at least one microchannel includes a vertically extending microchannel and a longitudinally extending microchannel, and the filter is located between the vertically extending microchannel and the longitudinally extending microchannel.

5. The microfluidic chip of claim 1. comprising a filter chamber in fluid communication with the viewing area downstream of the viewing area, the filter chamber including the filter.

6. The microfluidic chip of claim 1, comprising at least one microchannel placing the input area, the viewing area and the output area in fluid communication.

6. The microfluidic chip of claim 1, wherein at least one microchannel includes a first microchannel and a second microchannel, the first microchannel placing the input area in fluid communication with the viewing area, the second microchannel placing the viewing area in fluid communication with the output area.

7. The microfluidic chip of claim 1. wherein the input area includes an input silo configured to initially receive the cells obtained from the patient and to enable the cells to be withdrawn after the cells have been viewed in the viewing area.

8. The microfluidic chip of claim 1, wherein the output area includes an output silo having an inner area fluidly connected to the viewing area, the output silo having an entry7point located at a height above the viewing area.

9. The microfluidic chip of claim 1. wherein the output area includes an output silo having an inner area fluidly connected to the viewing area and an air vent to release air from the inner area as the fluid enters.

10. A method of enabling cells to undergo a visual diagnostic and be preserved for a molecular diagnostic, the method comprising: inputting the cells into an input area of a microfluidic chip; inputting a fluid into the input area of the microfluidic chip; applying pressure at the input area to cause the cells to flow into a viewing area of the microfluidic chip and the fluid to flow into an output area of the microfluidic trip; viewing the cells within the view ing area; and w ithdrawing at least some of the cells from the viewing area back into the input area while at least some of the fluid remains in the output area.

11. The method of claim 10, comprising inputing a dyed fluid into the input area of the microfluidic chip, applying pressure at the input area to cause the cells mixed with the dyed fluid to flow into the viewing area, inputing a clear fluid into the input area of the microfluidic chip, and applying pressure at the input area to cause the clear fluid to push the dyed fluid into the output area.

12. The method of claim 10, comprising withdrawing at least some of the cells from the input area into a needle or pipete.

13. The method of claim 10, wherein viewing the cells within the viewing area includes viewing the cells through a viewing window' while the cells are located in a viewing chamber.

14. The method of claim 10, wherein inputing the cells into the input area includes adding the cells into an input silo.

15. The method of claim 14, wherein inputing the fluid into the input area includes adding the fluid into the input silo.

16. The method of claim 10, wherein applying pressure at the input area to cause the cells to flow7into the viewing area and the fluid to flow into the output area includes driving the fluid downstream of a filter while the filter prevents at least some of the cells from traveling downstream.

17. A microfluidic chip enabling cells to undergo both a visual diagnostic and a molecular diagnostic, the microfluidic chip comprising: a body including an upper surface and a lower surface extending in a longitudinal direction from a first end to a second end and in a lateral direction from a first lateral side to a second lateral side;an input area including an input silo configured to receive cells obtained from a patient; an output area including an output silo; at least one microchannel placing the input silo and the output silo in fluid communication; and a viewing area in fluid communication with the at least one microchannel and configured to enable the visual diagnostic of the cells that have flowed through the at least one microchannel.

18. The microfluidic chip of claim 17, wherein the viewing area includes a viewing chamber, and the microfluidic chip includes a filter located below the viewing chamber.

19. The microfluidic chip of claim 17, wherein the at least one microchannel places the viewing area and the output area in fluid communication, the microfluidic chip includes a filter located along the at least one microchannel dow stream of the viewing area.

20. The microfluidic chip of claim 19, wherein the at least one microchannel includes a vertically extending microchannel and a longitudinally extending microchannel, and the filter is located between the vertically extending microchannel and the longitudinally extending microchannel.

21. The microfluidic chip of claim 17, comprising a filter chamber in fluid communication with the viewing area downstream of the viewing area, the filter chamber including a filter.

22. The microfluidic chip of claim 17, wherein the at least one microchannel includes a first microchannel and a second microchannel,the first microchannel placing the input area in fluid communication with the viewing area, the second microchannel placing the viewing area in fluid communication with the output area.

23. The microfluidic chip of claim 17, wherein the input silo is configured to initially receive the cells obtained from the patient and to enable the cells to be withdrawn after the cells have been viewed in the viewing area.

24. The microfluidic chip of claim 17, wherein the output silo has an inner area fluidly connected to the viewing area and an entry point located at a height above the viewing area.

25. The microfluidic chip of claim 17, wherein the output silo has an inner area fluidly connected to the viewing area and an air vent to release air from the inner area as the fluid enters.

26. The microfluidic chip of claim 17, wherein the body is adjustable from a first orientation to a second orientation, the input silo and the output silo extend from the body in opposite directions in the first orientation, and the input silo and the output silo extend from the body in a same direction in the second orientation.

27. The microfluidic chip of claim 17, wherein the body includes a first part and a second part, the first part includes the input area, the second part includes the output area, and the second part is configured to move with respect to the first part so that the output silo extends from the upper surface in a same direction as the input silo.

28. The microfluidic chip of claim 19, whereinthe second part includes a partial microchannel that is placed in fluid communication with the at least one microchannel when the second part moves so that the output silo extends from the upper surface in the same direction as the input silo.

29. The microfluidic chip of claim 17, wherein the at least one microchannel includes a first microchannel and a second microchannel, and the viewing area is located between the first microchannel and the second microchannel in the longitudinal direction.

30. The microfluidic chip of claim 29, wherein the viewing area is wider than the first microchannel and the second microchannel in the lateral direction.

31. A system comprising the microfluidic chip of claim 17 and a supportive device configured to mount the microfluidic chip and align a magnetic force with the viewing area.

32. A supportive device enabling cells to undergo both a visual diagnostic and a molecular diagnostic, the supportive device comprising a microfluidic chip mount configured to removably receive a microfluidic chip in an orientation in which cells can be deposited at an input area of the microfluidic chip and flow through the microfluidic chip via capillary action; and an alignment arm including a magnet, the alignment arm configured to move with respect to the microfluidic chip mount to translate the magnet into and out of alignment with a viewing area of the microfluidic chip when the microfluidic chip is mounted on the microfluidic chip mount.

33. The supportive device of claim 32, wherein the alignment arm is configured to translate the magnet vertically beneath the viewing area of the microfluidic chip to place the magnet into alignment with the viewing area.

34. The supportive device of claim 32, comprising an output container positioned vertically beneath an output area of the microfluidic chip when the microfluidic chip is mounted on the microfluidic chip mount.

35. The supportive device of claim 34, comprising a base attaching the microfluidic chip mount, the alignment arm and the output container.

36. The supportive device of claim 32, wherein the alignment arm includes a first end and a second end, the first end includes the magnet, and the second end is configured to be gripped by a user to cause the alignment arm to translate the magnet into and out of alignment with the viewing area of the microfluidic chip.

37. The supportive device of claim 32, wherein the microfluidic chip mount includes a first side mount and a second side mount, the first side mount includes a first indentation configured to receive one end of the microfluidic chip, and the second side mount includes a second indentation configured to receive an opposite end of the microfluid chip.

38. A system comprising the supportive device of claim 32 and the microfluidic chip having the input area and the viewing area.

39. A method enabling cells to undergo both a visual diagnostic and a molecular diagnostic, the method comprising: depositing cells attached to immunomagnetic beads into an input area in fluid communication with at least one microchannel such that the cells attached to the immunomagnetic beads flow from the input area through the at least one microchannel; aligning a magnetic force with a viewing area in fluid communication with the at least one microchannel so that the cells attached to the immunomagnetic beads collect in the viewing area for the visual diagnostic; andenabling the cells attached to the immunomagnetic beads to flow to an output area in fluid communication with the viewing area to be collected for the molecular diagnostic.

40. The method of claim 39, comprising extracting the cells from a patient during a fine needle aspiration procedure.

41. The method of claim 39, wherein aligning the magnetic force with the viewing area includes translating a magnet into a location beneath the viewing area.

42. The method of claim 39, wherein enabling the cells attached to the immunomagnetic beads to flow to the output area includes translating the magnetic force away from the viewing area.

43. The method of claim 39, comprising mounting a microchip including the input area, the at least one viewing area and the microchannel onto a supportive device prior to depositing the cells attached to the immunomagnetic beads into the input area.

44. The method of claim 43, comprising adjusting an orientation of the microfluidic chip after the visual diagnostic to prevent the cells attached to magnetic beads from further flowing out of the output area via capillary action.

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