Apparatus and method for control of fluid flow

Abstract

A first fluidic channel of an apparatus receives a fluid containing particles and has a first fluid flow resistance. A second fluidic channel receives a horizontal flow control fluid and has a second fluid flow resistance. A third fluidic channel receives the horizontal flow control fluid and has a third fluid flow resistance. The first fluidic channel, the second fluidic channel, and the third fluidic channel are joined together at a first junction. A first outlet channel extends from the first junction to convey fluid from the first junction and has a fourth fluid flow resistance. The first fluid flow resistance is lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

Description

APPARATUS AND METHOD FOR CONTROL OF FLUID FLOWCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 539,612, filed September 21, 2023; U.S. Provisional Application No. 63 / 539,613, filed September 21, 2023 ; Application Serial No. NL 2036029, filed October 13, 2023 ; and Application Serial No. NL 2036031, filed October 13, 2023, each of which is incorporated herein by reference.BACKGROUND

[0002] The properties of cells may be analyzed to diagnose diseases and other conditions. Such analysis may include evaluation of cell morphology to determine cell type (e.g., stem cell or differentiated cell) or cell state (e.g., healthy state or disease state). In some cases, cells may be directed through a channel of a cartridge, under fluidic guidance, through a microscope imaging field. The images captured through the microscope may be processed to evaluate cell morphology. While a variety of devices, systems, and methods have been made and used to process and analyze cells, there is an unmet need for approaches that overcome inherent limitations of conventional methods.SUMMARY

[0003] Provided herein is an apparatus, comprising: a first fluidic channel to receive a fluid containingparticles, the firstfluidic channel having a first fluid flow resistance; a second fluidic channel to receive a horizontal flow control fluid, the second fluidic channel having a second fluid flow resistance; a third fluidic channel to receive the horizontal flow control fluid, the third fluidic channel having a third fluid flow resistance; a first junction, the first fluidic channel, the second fluidic channel, and the third fluidic channel joining together at the first junction; and a first outlet channel extending from the first junction to convey fluid from the first junction, the first outlet channel having a fourth fluid flow resistance; the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

[0004] In some embodiments, the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other. In some embodiments, the first fluid flowresistance rangingfrom approximately 1 / 5 of the second fluid flow resistance to approximately U of the second fluid flow resistance. In some embodiments,the first fluid flow resistance ranging from approximately 1 / 5 of the third fluid flow resistance to approximately Yi of the third fluid flow resistance. In some embodiments, the first fluid flow resistance ranging from approximately 1 / 5 of the fourth fluid flow resistance to approximately / i of the fourth fluid flow resistance. In some embodiments, the first fluidic channel having a first length, the second fluidic channel having a second length, the third fluidic channel having a third length, the first outlet channel having a fourth length; and the first length being substantially shorter than each of the second length, the third length, and the fourth length. In some embodiments, the second length, the third length, and the fourth length being approximately equal to each other. In some embodiments, the first fluidic channel extending along a first horizontal dimension. In some embodiments, the first outlet channel extending along the first horizontal dimension. In some embodiments, the first fluidic channel and the first outlet channel being aligned with each other along the first horizontal dimension.

[0005] In some embodiments, the second fluidic channel extending along a second horizontal dimension. In some embodiments, the third fluidic channel extending along the second horizontal dimension. In some embodiments, the first fluidic channel being substantially perpendicular to the second fluidic channel at the junction. In some embodiments, the first fluidic channel being substantially perpendicular to the third fluidic channel at the junction. In some embodiments, the first outlet channel being substantially perpendicular to the second fluidic channel at the junction. In some embodiments, the first outlet channel being substantially perpendicular to the third fluidic channel atthe junction. In some embodiments, the horizontal flow control fluid from the second fluidic channel to focus the flow of the fluid containing particles in a first direction in a first horizontal dimension as the fluid containing particles flows along a second horizontal dimension within the first outlet channel, the horizontal flow control fluid from the third fluidic channel to focus the flow of the fluid containing particles in a second direction in the first horizontal dimension as the fluid containingparticles flows alongthe secondhorizontal dimensionwithin the first outlet channel.

[0006] In some embodiments, the second fluidic channel including a mixing feature, the third fluidic channel including a mixing feature. In some embodiments, the mixing feature of the second fluidic channel including a set of recesses, the mixing f eature of the third fluidic channel including a set of recesses. In some embodiments, the set of recesses of the second fluidic channel being in an upper surface of the second fluidic channel, the set of recesses of the third fluidic channel being in an upper surface of the third fluidic channel. In some embodiments, the set of recesses of the second fluidic channel including chevron shaped recesses, the set of recesses of the third fluidic channel including chevron shaped recesses. In some embodiments,the mixing feature of the second fluidic channel to provide randomized arrangement of particles flowing through the second fluidic channel, the mixing feature of the third fluidic channel to provide randomized arrangement of particles flowing through the third fluidic channel.

[0007] In some embodiments, the apparatus further comprises a vertical flow focusing feature, the vertical flow focusing feature to cause a vertical flow focusing fluid to focus the position of the particles along a vertical dimension within the first outlet channel as the particles flow along a horizontal dimension through the outlet channel. In some embodiments, the apparatus further comprises a fourth fluidic channel to provide the vertical flow focusing fluid to the vertical flow focusing feature. In some embodiments, the apparatus further comprises a fifth fluidic channel to provide the vertical flow focusing fluid to the vertical flow focusing feature. In some embodiments, the apparatus further comprises a second junction, the fourth fluidic channel and the fifth fluidic channel joining together at the second junction. In some embodiments, the vertical flow focusing feature being positioned at the second junction.

[0008] In some emb odiments, the apparatus further comprises a sixth fluidic channel extending between the first junction and the secondjunction. In some embodiments, the secondjunction being positioned upstream of the first junction. In some embodiments, the vertical flow focusing feature comprising a channel extending along a vertical dimension. In some embodiments, the channel comprising a recess in a bottom surface of a layer. In some embodiments, the channel having a cylindrical shape. In some embodiments, the cylindrical shape having a diameter along a horizontal dimension, the first outlet channel having a width along the horizontal dimension, the diameter being greater than the width.

[0009] In some embodiments, the apparatus further comprises a sample fluid receiving region, the sample fluid receiving region including a recess with a tapered region leading toward the first fluidic channel. In some embodiments, the apparatus further comprises a fourth fluidic channel extending from the tapered region, the vertical flow focusing feature being positioned in a fluid path between the fourth fluidic channel and the first fluidic channel. In some embodiments, the vertical flow focusing feature being positioned in the tapered region of the sample fluid receiving region.

[0010] In some embodiments, the vertical flow focusingfeaturecomprising: a recess extending along a horizontal dimension, and a channel extending along a vertical dimension over the recess. In some embodiments, the recess has a circular shape. In some embodiments, the channel has a cylindrical shape. In some embodiments, the recess has a first diameter, the channel has a second diameter, the second diameter is different from the first diameter. In some embodiments, the second diameter is smaller than the first diameter. In some embodiments, thesecond diameter is largerthan the first diameter. In some embodiments, the first fluidic channel, the second fluidic channel, the third fluidic channel, the first outlet channel, and the recess extend alonga shared horizontal plane. In someembodiments, the recess maybe centered along a first vertical axis, and the channel being centered along a second vertical axis. In some embodiments, the second vertical axis may be offset from the first vertical axis along a horizontal dimension. In some embodiments, the first fluidic channel and the first outlet channel to convey fluids along the same horizontal dimension along which the second vertical axis is offset from the first vertical axis. In some embodiments, the vertical flow focusing feature being centered along a vertical axis, the first fluidic channel and the first outlet channel to convey fluids along a longitudinal axis extending along a first horizontal dimension, and the vertical axis being laterally offset from the longitudinal axis along a second horizontal dimension.

[0011] In some embodiments, the apparatus further comprises a plurality of layers, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature extending through or along one or more of the layers of the plurality of layers. In some embodiments, at least one layer of the plurality of layers comprises polydimethylsiloxane (PDMS). In some embodiments, a first layer of the plurality of layers comprising PDMS has a first thickness, and a second layer of the plurality of layers comprising PDMS has a second thickness. In some embodiments, the plurality of layers comprises a layer of glass. In some embodiments, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature comprises one or more respective recesses extending along one layer of the plurality of layers.

[0012] In some embodiments, the apparatus further comprises an imagingregion alongthe first outlet channel to image particles conveyed along the first outlet channel.

[0013] In some embodiments, the apparatus further comprises: a second outlet channel; a third outlet channel; and a sorting junction at an end of the first outlet channel, the sorting junction leading to the second outlet channel and the third outlet channel.

[0014] In some embodiments, the apparatus further comprises: a first valve and a second valve, the first valve to selectively permit or prevent flow of fluid through the second outlet channel, the second valve to selectively permit or prevent flow of fluid through the third outlet channel.

[0015] In some embodiments, the apparatus further comprises: a plurality of wells; and a plurality of additional fluidic channels, each additional fluidic channel of the plurality of additional fluidic channels leading to a respective well of the plurality of wells.

[0016] In some embodiments, the apparatus further comprises: a plurality of valves, each valve of the plurality of valves to selectively permit or prevent flow of fluid through a respective additional fluidic channel of the plurality of additional fluidic channels.

[0017] In some embodiments, the apparatus further comprises: a sample fluid receiving region, the first fluidic channel to receive a fluid containing particles from an external source via the sample fluid receiving region. In some embodiments, the sample fluid receives region including a recess having a teardrop shape. In some embodiments, the sample fluid receives region including a plurality of filtering elements.

[0018] In some aspects, the present disclosure provides a method comprising: flowing a fluid containing particles along a first fluidic channel at a first fluid flow resistance; flowing a flow control fluid along a second fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel at a second fluid flow resistance; flowing the flow control fluid along a third fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel and while simultaneously flowing the flow control fluid along the second fluidic channel at a third fluid flow resistance; and allowing the flow of the fluid containing particles alongthe first fluidic channel to join the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid alongthe third fluidic channel atajunction, thereby forming a joined fluid, the joined fluid exiting the junction along a first outlet channel and flowing at a fourth fluid flow resistance; the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

[0019] In some embodiments, the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other. In some embodiments, the first fluid flowresistance rangingfrom approximately 1 / 5 of the second fluid flow resistance to approximately Yi of the second fluid flow resistance. In some embodiments, the first fluid flow resistance ranging from approximately 1 / 5 of the third fluid flow resistance to approximately Yi of the third fluid flow resistance. In some embodiments, the first fluid flow resistance ranging from approximately 1 / 5 of the fourth fluid flow resistance to approximately / i of the fourth fluid flow resistance. In some embodiments, the first fluidic channel having a first length, the second fluidic channel having a second length, the third fluidic channel having a third length, the first outlet channel having a fourth length; flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the first length; flowing the flow control fluid along the second fluidic channel including flowingthe flow control fluid alongthe second length; and flowingthe flow control fluid alongthe third fluidic channel including flowing the flow control fluid along the third length; the j oined fluid flowing along the f ourth length of the first outlet channel; and the first length b eing substantially shorter than each of the second length, the third length, and the fourth length.

[0020] In some embodiments, the second length, the third length, and the fourth length being approximately equal to each other. In some embodiments, the first fluidic channel extending along a first horizontal dimension; and flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the first horizontal dimension. In some embodiments, the first outlet channel extending along the first horizontal dimension; the joined fluid flowing along the first outlet channel along the first horizontal dimension. In some embodiments, the first fluidic channel and the first outlet channel being aligned with each other along the first horizontal dimension. In some embodiments, the second fluidic channel extending along a second horizontal dimension; and flowing the flow control fluid alongthe second fluidic channel including flowingthe flow control fluid along the second horizontal dimension. In some embodiments, the third fluidic channel extending along the second horizontal dimension; and flowingthe flow control fluid alongthe third fluidic channel including flowing the flow control fluid along the second horizontal dimension.

[0021] In some embodiments, the first fluidic channel being substantially perpendicular to the second fluidic channel at the junction. In some embodiments, the first fluidic channel being substantially perpendicular to the third fluidic channel atthe junction. In some embodiments, the first outlet channel being substantially perpendicular to the second fluidic channel at the junction. In some embodiments, the first outlet channel being substantially perpendicularto the third fluidic channel at the junction. In some embodiments, the flow control fluid from the second fluidic channel focusing the flow of the fluid containing particles in a first direction in a first horizontal dimension as the fluid containing particles flows along a second horizontal dimension within the first outlet channel, the flow control fluid from the third fluidic channel focusing the flow of the fluid containing particles in a second direction in the first horizontal dimension as the fluid containing particles flows along the second horizontal dimension within the first outlet channel. In some embodiments, flowingthe fluid containing particles alongthe first fluidic channel including flowing the fluid containing particles along a first horizontal dimension. In some embodiments, flowing the flow control fluid along the second fluidic channel including flowingthe flow control fluid along a second horizontal dimension into the junction. In some embodiments, flowingthe flow control fluid alongthe second fluidic channel further includingflowingthe flow control fluid along a serpentine path before flowingthe flow control fluid alongthe second horizontal dimension into the junction. In some embodiments,flowingthe flow control fluid alongthe third fluidic channel includingflowingthe flow control fluid alongthe second horizontal dimension into the junction. In some embodiments, flowing the flow control fluid along the third fluidic channel further including flowing the flow control fluid along a serpentine path before flowing the flow control fluid alongthe second horizontal dimension into the junction. In some embodiments, the flow control fluid from the second fluidic channel focusing the position of the particles in a first direction alongthe a horizontal dimension within the outlet channel as the particles flow along a second horizontal dimension. In some embodiments, the flow control fluid from the third fluidic channel focusing the position of the particles in a second direction alongthe first horizontal dimension within the outlet channel as the particles flow along the second horizontal dimension.

[0022] In some embodiments, flowing the flow control fluid along the second fluidic channel includingflowingthe flow control fluid through a mixingfeature of the second fluidic channel; and flowing the flow control fluid alongthe third fluidic channel includingflowingthe flow control fluid through a mixing feature of the third fluidic channel. In some embodiments, the mixing feature of the second fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the second fluidic channel including flowing the flow control fluid alongthe set of recesses of the mixing feature of the second fluidic channel; and the mixing feature of the third fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the third fluidic channel including flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel. In some embodiments, the set of recesses of the second fluidic channel being in an upper surface of the second fluidic channel, flowing the flow control fluid alongthe set of recesses of the mixing feature of the second fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the second fluidic channel; and the set of recesses of the third fluidic channel being in an upper surface of the third fluidic channel, flowing the flow control fluid alongthe set of recesses of the mixingfeature ofthe third fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the third fluidic channel.

[0023] In some embodiments, the mixing feature of the second fluidic channel providing randomized arrangement of particles flowing through the second fluidic channel, the mixing feature of the third fluidic channel providing randomized arrangement of particles flowing through the third fluidic channel.

[0024] In some embodiments, the method further comprises flowing a vertical flow focusing fluid through a vertical flow focusing feature to focus the position of the particles along avertical dimension within the first outlet channel as the particles flow along a horizontal dimension through the outlet channel. In some embodiments, the method further comprises flowing the vertical flow focusing fluid through a fourth fluidic channel to thereby provide the vertical flow focusing fluid to the vertical flow focusing feature. In some embodiments, the method further comprises flowing the vertical flow focusing fluid through a fifth fluidic channel to thereby provide the vertical flow focusing fluid to the vertical flow focusing feature. In some embodiments, the method further comprises flowing the vertical flow focusing fluid through a second junction, the fourth fluidic channel and the fifth fluidic channel joining together at the second junction.

[0025] In some embodiments, the vertical flow focusing feature being positioned at the second junction. In some embodiments, the vertical flow focusing feature comprising a channel extending along a vertical dimension, flowing the vertical flow focusing fluid through the vertical flow focusing feature including flowing the vertical flow focusing fluid along the vertical dimension. In some embodiments, the channel comprising a recess in a bottom surface of a layer, flowing the vertical flow focusing fluid through the vertical flow focusing feature including flowing the vertical flow focusing fluid into the recess. In some embodiments, the channel having a cylindrical shape. In some embodiments, the cylindrical shape having a diameter along a horizontal dimension, the first outlet channel having a width along the horizontal dimension, the diameter being greater than the width.

[0026] In some embodiments, the vertical flow focusingfeaturecomprising: a recess extending along a horizontal dimension, and a channel extending along a vertical dimension over the recess; and flowing the vertical flow focusing fluid through the vertical flow focusing feature including flowing the vertical flow focusing fluid into the channel and into the recess.

[0027] In some embodiments, the recess having a circular shape. In some embodiments, the channel having a cylindrical shape. In some embodiments, the recess having a first diameter, the channel having a second diameter, the second diameter being different from the first diameter. In some embodiments, the second diameter being smaller than the first diameter. In some embodiments, the second diameter being larger than the first diameter.

[0028] In some embodiments, the first fluidic channel, the second fluidic channel, the third fluidic channel, the first outlet channel, and the recess extending along a shared horizontal plane; flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the shared horizontal plane; flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along the shared horizontal plane; flowing the flow control fluid along the third fluidic channel includingfl owing the flow control fluid along the shared horizontal plane; and the joined fluid flowing along the shared horizontal plane while flowing along the first outlet channel.

[0029] In some embodiments, the recess being centered along a first vertical axis, the channel being centered along a second vertical axis. In some embodiments, the second vertical axis being offset from the first vertical axis along a horizontal dimension.

[0030] In some embodiments, flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the same horizontal dimension along which the second vertical axis is offset from the first vertical axis; and the joined fluid flowing along the same horizontal dimension along which the second vertical axis is offset from the first vertical axis.

[0031] In some embodiments, the vertical flow f ocusing f eature b eing centered along a vertical axis; flowing the fluid containing particles along the first fluidic channel including flowing the fluid containingparticles along a longitudinal axis extending along a first horizontal dimension, the vertical axis being laterally offset from the longitudinal axis along a second horizontal dimension; and the joined fluid flowing along the longitudinal axis.

[0032] In some embodiments, the method further comprises capturing images of particles as the particles are conveyed along the first outlet channel. In some embodiments, the method further comprises classifying or identifying the particles by analyzing the captured images. In some embodiments, the method further comprises sorting particles from the outlet channel in response to classifying or identifying the particles by analyzing the captured images.

[0033] In some embodiments, sorting particles including activating one or more valves to redirect fluid flow from the outlet channel to another outlet channel selected from a plurality of other outlet channels.

[0034] In some embodiments, the particles including biological cells.

[0035] In some aspects, the present disclosure also provides an apparatus, comprising: a first fluidic channel to receive a fluid containingparticles; a second fluidic channel to receive a flow control fluid; a third fluidic channel to receive the flow control fluid; a junction, the first fluidic channel, the second fluidic channel, and the third fluidic channel joining together at the junction; a first outlet channel extending from the junction to convey fluid from the junction; and a flow focusing feature positioned at the junction, the flow focusing feature to cause the flow control fluid from the second fluidic channel and the third fluidic channel to focus the position of the particles along a vertical dimension and along a first horizontal dimension within the first outlet channel as the particles flow along a second horizontal dimension through the outlet channel.

[0036] In some embodiments, the second fluidic channel and the third fluidic channel having mirror symmetry with each other. In some embodiments, the flow focusing feature comprising a recess positioned above the junction. In some embodiments, the recess extending over a portion of the second fluidic channel. In some embodiments, the recess extending over a portion of the third fluidic channel. In some embodiments, the first fluidic channel having a width extending alongthe horizontal dimension, the recess having a length extending alongthe horizontal dimension, the length of the recess being greater than the width of the first fluidic channel. In some embodiments, the recess having a rectangular shape. In some embodiments, the first fluidic channel extending along the second horizontal dimension. In some embodiments, the first outlet channel extending along the second horizontal dimension. In some embodiments, the first fluidic channel and the second fluidic channel being aligned with each other along the second horizontal dimension. In some embodiments, the second fluidic channel extending alongthe first horizontal dimension. In some embodiments, the third fluidic channel extending along the first horizontal dimension. In some embodiments, the second fluidic channel and the third fluidic channel being aligned with each other along the first horizontal dimension. In some embodiments, the first fluidic channel being perpendicular to the second fluidic channel at the junction. In some embodiments, the first fluidic channel being perpendicular to the third fluidic channel at the junction. In some embodiments, the first outlet channel being perpendicular to the second fluidic channel at the junction. In some embodiments, the first outlet channel being perpendicular to the third fluidic channel at the junction. In some embodiments, the flow focusing feature to cause the flow control fluid from the second fluidic channel and the third fluidic channel to flow in a first direction along the vertical dimension and then in a second direction along the vertical dimen sion to thereby focus the position of the particles in the second direction alongthe vertical dimension within the first outlet channel as the particles flow along a second horizontal dimension. In some embodiments, the flow control fluid from the second fluidic channel to focus the position of the particles in a first direction alongthe first horizontal dimension within the first outlet channel as the particles flow alongthe second horizontal dimension. In some embodiments, the flow control fluid from the third fluidic channel to focus the position of the particles in a second direction alongthe first horizontal dimension within the first outlet channel as the particles flow alongthe second horizontal dimension. In some embodiments, the first fluidic channel having a first fluid flow resistance, the second fluidic channel having a second fluid flow resistance, the third fluidic channel having a third fluid flow resistance, the first outlet channel having a fourth fluid flow resistance; and the first fluid flow resistance being lower than each of the second fluid flowresistance, the third fluid flow resistance, and the fourth fluid flow resistance.

[0037] In some embodiments, the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other. In some embodiments, the second fluidic channel including a mixing feature, and the third fluidic channel including a mixing feature. In some embodiments, the mixing feature of the second fluidic channel including a set of recesses, and the mixing feature of the third fluidic channel including a set of recesses. In some embodiments, the set of recesses of the second fluidic channel being disposed over an upper surface of the second fluidic channel, and the set of recesses of the third fluidic channel being disposed over an upper surface of the third fluidic channel. In some embodiments, the set of recesses of the second fluidic channel including chevron shaped recesses, and the set of recesses of the third fluidic channel including chevron shaped recesses. In some embodiments, the mixing feature of the second fluidic channel to provide randomized arrangement of particles flowing through the second fluidic channel, and the mixing feature of the third fluidic channel to provide randomized arrangement of particles flowing through the third fluidic channel.

[0038] In some embodiments, the apparatus further comprises a plurality of layers, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature extending through or along one or more of the layers of the plurality of layers. In some embodiments, at least one layer of the plurality of layers comprising poly dimethylsiloxane (PDMS). In some embodiments, a first layer of the plurality of layers comprisingPDMS having a first thickness, and a second layer of the plurality of layers comprising PDMS having a second thickness. In some embodiments, the plurality of layers comprising a layer of glass. In some embodiments, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature comprising one or more respective recesses extending along one layer of the plurality of layers.

[0039] In some embodiments, the apparatusfurther comprises an imagingregion alongthe first outlet channel to image particles conveyed along the first outlet channel.

[0040] In some embodiments, the apparatus further comprises: a second outlet channel; a third outlet channel; and a sorting junction at an end of the first outlet channel, the sorting junction leading to the second outlet channel and the third outlet channel.

[0041] In some embodiments, the apparatus further comprises a first valve and a second valve, the first valve to selectively permit or prevent flow of fluid through the second outlet channel, the second valve to selectively permit or prevent flow of fluid through the third outlet channel.

[0042] In some embodiments, the apparatus further comprises: a plurality of wells; and a plurality of additional fluidic channels, each additional fluidic channel of the plurality of additional fluidic channels leading to a respective well of the plurality of wells.

[0043] In some embodiments, the apparatus further comprises a plurality of valves, each valve of the plurality of valves to selectively permit or prevent flow of fluid through a respective additional fluidic channel of the plurality of additional fluidic channels.

[0044] In some embodiments, the apparatus further comprises a sample fluid receiving region, the first fluidic channel to receive a fluid containing particles from an external source via 1he sample fluid receiving region. In some embodiments, the sample fluid receiving region including a recess having a teardrop shape. In some embodiments, the sample fluid receiving region including a plurality of filtering elements.

[0045] In some aspects, the present disclosure also relates to a method comprising: flowing a fluid containing particles along a first fluidic channel; flowing a flow control fluid along a second fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel; flowing the flow control fluid along a third fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel and while simultaneously flowing the flow control fluid along the second fluidic channel; and allowing the flow of the fluid containing particles along the first fluidic channel to join the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel at a junction, thereby forming a joined fluid, thejunction including an outlet channel and a flow focusing feature; the flow focusing feature causing the flow control fluid from the second fluidic channel and the third fluidic channel to focus the position of the particles along a vertical dimension and along a first horizontal dimension within the outlet channel as the particles flow in the joined fluid along a second horizontal dimension through the outlet channel.

[0046] In some embodiments, the flow focusing feature comprising a recess positioned above the junction, allowing the flow of the fluid containing particles along the first fluidic channel to join the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel at the junction comprising allowing the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel to enter the recess positioned above the junction. In some embodiments, the flow control fluid from the second fluidic channel and the flow control fluid from the third fluidic channel flowing upwardly into the recess then downwardly toward the outlet channel. In some embodiments, flowing the fluid containing particles along the firstfluidic channel including flowing the fluid containing particles along the second horizontal dimension. In some embodiments, flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along the first horizontal dimension into the junction. In some embodiments, flowing the flow control fluid alongthe second fluidic channel further includingflowingthe flow control fluid along a serpentine path before flowing the flow control fluid along the first horizontal dimension into the junction. In some embodiments, flowingthe flow control fluid alongthe third fluidic channel includingflowingthe flow control fluid alongthe first horizontal dimension into the junction. In some embodiments, flowingthe flow control fluid along the third fluidic channel further including flowingthe flow control fluid along a serpentine path before flowingthe flow control fluid along the first horizontal dimension into the junction. In some embodiments, the flow control fluid from the second fluidic channel focusingthe position of the particles in a first direction alongthe first horizontal dimension within the outlet channel as the particles flow along the second horizontal dimension. In some embodiments, the flow control fluid from thethird fluidic channel focusing the position of the particles in a second direction alongthe first horizontal dimension within the outlet channel as the particles flow along the second horizontal dimension.

[0047] In some embodiments, the fluid containing particles flowing along the first fluidic channel at a first fluid flow resistance; the flow control fluid flowing alongthe second fluidic channel at a second fluid flow resistance; the flow control fluid flowing along the third fluidic channel at a third fluid flow resistance; the joined fluid flowing through the outlet channel at a fourth fluid flow resistance; and the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flowresistance, and the fourth fluid flow resistance.

[0048] In some embodiments, the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other. In some embodiments, flowingthe flow control fluid alongthe second fluidic channel including flowing the flow control fluid through a mixing feature of the second fluidic channel; and flowingthe flow control fluid along the third fluidic channel including flowing the flow control fluid through a mixing feature of the third fluidic channel.

[0049] In some embodiments, the mixing feature of the second fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the second fluidic channel including flowing the flow control fluid along the set of recesses of the mixing feature of the second fluidic channel; and the mixing feature of the third fluidic channel including a set of recesses, flowingthe flow control fluid through the mixing feature of the third fluidic channel includingflowingthe flow control fluid alongthe set of recesses of the mixing featureof the third fluidic channel. In some embodiments, the set of recesses of the second fluidic channel being disposed over an upper surface of the second fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the second fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the second fluidic channel; and the set of recesses of the third fluidic channel b eing disposed over an upper surface of the third fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the third fluidic channel.

[0050] In some embodiments, the mixing feature of the second fluidic channel providing randomized arrangement of particles flowing through the second fluidic channel, the mixing feature of the third fluidic channel providing randomized arrangement of particles flowing through the third fluidic channel.

[0051] In some embodiments, the method further comprises capturing images of particles as the particles are conveyed along the outlet channel.

[0052] In some embodiments, the method further comprises classifying the particles by analyzing the captured images.

[0053] In some embodiments, the method further comprises sorting particles from the outlet channel in response to classifying or identifyingthe particles by analyzing the captured images. In some embodiments, sortingparticles including activating one or more valves to redirect fluid flow from the outlet channel to another outlet channel selected from a plurality of other outlet channels. In some embodiments, the particles including biological cells.

[0054] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.INCORPORATION BY REFERENCE

[0055] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.BRIEF DESCRIPTION OF THE DRAWINGS

[0056] FIG. 1 depicts a schematic view of an example of a cell analysis system.

[0057] FIG. 2 depicts a perspective view of an example of a cartridge that may be used in examples of the cell analysis system of FIG. 1.

[0058] FIG. 3 depicts an exploded perspective view of the cartridge of FIG. 2.

[0059] FIG. 4 depicts a perspective view of an example underside of a first layer of the cartridge of FIG. 2.

[0060] FIG. 5 depicts a perspective view of an example underside of a second layer of the cartridge of FIG. 2.

[0061] FIG. 6 depicts a top plan view of the cartridge of FIG. 2.

[0062] FIG. 7 depicts an enlarged view of an example fluid input region of the cartridge of FIG. 2.

[0063] FIG. 8 depicts an enlarged view of an example mixing structure ofthe fluid input region of FIG. 7.

[0064] FIG. 9 depicts a cross-sectional view of the mixing structure of FIG. 8, taken along line 9-9 of FIG. 8.

[0065] FIG. 10 depicts a perspective schematic view of a portion of the mixing structure of FIG. 8.

[0066] FIG. 11 A depicts a schematic view of fluid flow dynamics in a portion of the fluid input region of FIG. 7 just upstream of the mixing structure of FIG. 8.

[0067] FIG. 1 IB depicts a schematic view of fluid flow dynamics in a portion of the fluid input region of FIG. 7 just downstream of the mixing structure of FIG. 8.

[0068] FIG. 12 depicts an enlarged view of another example of a fluid input region that may be incorporated into the cartridge of FIG. 2.

[0069] FIG. 13 depicts a perspective view, in side cross-section, of an example of a vertical flow focusing feature that may be incorporated into the fluid input region of FIG. 12, with the adjacent components of the fluid input region.

[0070] FIG. 14 depicts a top plan view of the flow focusing feature of FIG. 13, with the adjacent components of the fluid input region of FIG. 12.

[0071] FIG. 15 A depicts a schematic view of fluid dynamics in a portion of the fluid input region of FIG. 12 just upstream of the flow focusing feature of FIG. 13.

[0072] FIG. 15B depicts a schematic view of fluid dynamics in a portion of the fluid input region of FIG. 12 just downstream of the flow focusing feature of FIG. 13.

[0073] FIG. 16 depicts a perspective view, in side cross-section, of another example of a vertical flow focusing feature that may be incorporated into the fluid input region of FIG. 12, with the adjacent components of the fluid input region.

[0074] FIG. 17 depicts a top plan view of the flow focusing feature of FIG. 16, with the adjacent components of the fluid input region of FIG. 12.

[0075] FIG. 18 depicts a perspective view, in side cross-section, of another example of a vertical flow focusing feature that may be incorporated into the fluid input region of FIG. 12, with the adjacent components of the fluid input region.

[0076] FIG. 19 depicts a top plan view of the flow focusing feature of FIG. 18, with the adjacent components of the fluid input region of FIG. 12.

[0077] FIG. 20 depicts a perspective view, in side cross-section, of another example of a vertical flow focusing feature that may be incorporated into the fluid input region of FIG. 12, with the adjacent components of the fluid input region.

[0078] FIG. 21 depicts a top plan view of the flow focusing feature of FIG. 20, with the adjacent components of the fluid input region of FIG. 12.

[0079] FIG. 22 depicts a perspective view, in side cross-section, of another example of a vertical flow focusing feature that may be incorporated into the fluid input region of FIG. 12, with the adjacent components of the fluid input region.

[0080] FIG. 23 depicts a top plan view of the flow focusing feature of FIG. 22, with the adjacent components of the fluid input region of FIG. 12.

[0081] FIG. 24 depicts a perspective view of another example of a vertical flow focusing feature that may be incorporated into the fluid input region of FIG. 12, with the adjacent components of the fluid input region.

[0082] FIG. 25 depicts a top plan view of the flow focusing feature of FIG. 24, with the adjacent components of the fluid input region of FIG. 12.

[0083] FIG. 26 depicts a perspective view, in side cross-section, of another example of a vertical flow focusing feature that may be incorporated into the fluid input region of FIG. 12, with the adjacent components of the fluid input region.

[0084] FIG. 27 depicts a top plan view of the flow focusing feature of FIG. 26, with the adjacent components of the fluid input region of FIG. 12.

[0085] FIG. 28 depicts a schematic view of another example of a cartridge that may be used in examples of the cell analysis system of FIG. 1.

[0086] FIG. 29 depicts a perspective view of an example junction of the fluid input region of FIG. 7.

[0087] FIG. 29A depicts a perspective view of an example pair of junctions that may be incorporated into another example fluid input region of the cartridge of FIG. 2.

[0088] FIG. 30 depicts a cross-sectional view of the junction of FIG. 8, taken along 9 -9 of FIG. 29.

[0089] FIG. 31 depicts a cross-sectional view of the junction of FIG. 8, taken along 10-10 of FIG. 29.

[0090] FIG. 32 depicts a top schematic view of an example of fluid flow dynamics achieved through the junction of FIG. 29.

[0091] FIG. 33 depicts a bottom schematic view of the fluid flow dynamics of FIG. 32.

[0092] FIG. 34 depicts a side schematic view of the fluid flow dynamics of FIG. 32.

[0093] FIG. 35 depicts an end schematic view of the fluid flow dynamics of FIG. 32.

[0094] FIG. 36 depicts an enlarged view of an example mixing structure of the fluid input region of FIG. 7.DETAILED DESCRIPTION

[0095] The following detailed description of certain examples will be better understood when read in conjunction with the appended drawings. To the extent that the figures illustrate diagrams of the functional blocks of various examples, the functional blocks are not necessarily indicative of the division between hardware components. Thus, for example, one or more of the functional blocks (e.g., processors or memories) may be implemented in a single piece of hardware (e.g., a general purpose signal processor or random access memory, hard disk, or the like). Similarly, the programs may be stand-alone programs, may be incorporated as subroutines in an operating system, may be functions in an installed software package, and the like. It should be understood that the various examples are not limited to the arrangements and instrumentality shown in the drawings.

[0096] I. Terminology

[0097] Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise,” and variations such as “comprises” and “comprising” means various components may be co-jointly employedin the methodsand articles (e.g., compositions and apparatuses including device and methods). For example, the term “comprising” will be understood to imply the inclusion of any stated elements or steps but not the exclusion of any other elements or steps. In general, any of the apparatuses and methods described herein should be understood to be inclusive, but all or a sub-set of the components and / or steps mayaltematively be exclusive and may be expressed as “consisting of’ or alternatively “consisting essentially of’ the various components, steps, sub -components, or sub-steps. Furthermore, references to “one example” are not intended to be interpreted as excluding the existence of additional examples that also incorporate the recited features. The use of “including” “comprising,” “having,” or “in which,” and variations thereof, herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.

[0098] As used herein, the singular forms “a,” “an,” and “the” are intendedto include the plural forms as well, unless the context clearly indicates otherwise. As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “ / ”.

[0099] When used in the claims, the term “set” should be understood as one or more things which are grouped together. Similarly, when used in the claims “based on” should be understood as indicating that one thing is determined at least in part by what it is specified as being “based on.” Where one thing is required to be exclusively determined by another thing then that thing will be referred to as being “exclusively based on” that which it is determined by.

[0100] Spatially relative terms, such as “under,” “below,” “lower,” “over,” “upper,” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the term “unde may encompass both an orientation of over andunder. The devicemay be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly,” “downwardly,” “vertical,” “horizontal,” andthe like are used herein for the purpose of explanation only unless specifically indicated otherwise. In addition, terms such as “outer” and “inner” are used herein for purposes of description and are not intended to indicate or imply relative importance or significance.

[0101] When a feature or element is herein referred to as being “on” or “over” another feature or element, it may be directly on or over the other feature or element; or intervening features and / or elements may also be present. In other words, when a feature or element is herein referred to as being “on” or “over” another feature or element, it may be indirectly on or over the other feature or element. In contrast, when a feature or element is referred to asbeing “directly on” or “directly over” another feature or element, there are no intervening features or elements present.

[0102] When a feature or element is referred to as being “mounted,” “connected,” “supported,” “attached,” or “coupled” to another feature or element, it may be directly mounted, connected, supported, attached, or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being “directly mounted,” “directly connected,” “directly supported,” “directly attached,” or “directly coupled” to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown may apply to other embodiments. It will also be appreciated by those skilled in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.

[0103] As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, the terms “about” or “approximately” for any numerical values or ranges indicate a suitable dimensional tolerance, or other form of reasonable expected range, that allows the part or collection of components to function for its intended purpose as described herein. More specifically, “about” or “approximately” may refer to the range of values that are within ±10% of the recited value (e.g., “about 100” may refer to the range ofvaluesfrom 90to 110, including90, 110, 100, and all other values within the range of 90 and 110). Any numerical values given herein should also be understood to include about or approximately that value unless the context indicates otherwise. For example, if the value “ 10” is disclosed, then “about 10” is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. The terms “approximately” and “about’ are thus utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.

[0104] The term “substantially” is also utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue. The term “substantially” shall therefore be understood to include a range of conditions or results that provide a functional equivalent to an explicitly stated condition or result. For instance, if a task is “substantially complete,” the result of the task having been substantially completed is functionally equivalent to the result that would have been achieved if the task had been perfectly completed. As another nonlimiting example, a component that is “substantially straight” or “substantially flat,” anapparatus including a component that is “substantially straight” or “substantially flat” may provide a result or effect that is functionally equivalent to a result or effect that would be achieved by the same apparatus including the same component in a perfectly straight or perfectly flat configuration. The range implied by the term “substantially” should also be read to include the perfect result that is within that range. Thus, the term “substantially complete” shall be read as including “perfectly complete” while also including a range of completeness that is functionally equivalent to perfectly complete. As another example, terms such as “substantially straight” and “substantially flat” shall be read as including “perfectly straight’ and “perfectly flat,” respectively; while also including a range of straightness or flatness that is functionally equivalent to perfectly straight or flat, respectively. As with the terms “approximately” and “about,” the term “substantially” may indicate a suitable dimensional tolerance, or other form of reasonable expected range, that allows a part or collection of components to function for its intended purpose as described herein.

[0105] The term “perpendicular” shall be understood to include arrangements where one element (e.g., surface, feature, component, axis, etc.) defines an angle of 90 degrees with another element (e.g., surface, feature, component, axis, etc.). The term “perpendicular” shall also be understood to include arrangements where one element (e.g., surface, feature, component, axis, etc.) defines an angle of approximately 90 degrees with another element(e.g, surface, feature, component, axis, etc.).

[0106] It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value,” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “X” is disclosed the “less than or equal to X” as well as “greater than or equal to X” (e.g., where X is a numerical value) is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “ 10” and a particular data point “ 15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0107] Although the terms “first” and “second” may be used herein to describe various features / elements (including steps), these features / elements should not be limited by these terms, unless the context indicates otherwise. These terms are used to distinguish onefeature / element from another feature / element, and unless specifically pointed out, do not denote a certain order. Thus, a first feature / element discussed below could be termed a second feature / element, and similarly, a second feature / element discussed below could be termed a first feature / element without departing from the teachings of the present invention. The terms “first,” “second,” and“third,” etc. are thus used merely aslabels, andarenotintendedto impose numerical requirements on their objects.

[0108] As used herein, the terms “system,” “apparatus,” and “device” may be read as being interchangeable with each other. A system, apparatus, and device may each include a plurality of components having various kinds of structural and / or functional relationships with each other.

[0109] The term “fluid” shall be understood to include liquids and gases, including pneumatic pressure. Similarly, “fluidic communication” shall be understood to include the communication of liquids and the communication of gases, including pneumatic pressure.

[0110] The term “morphology” or “morphological characteristic” of a cell as used herein generally refers to the form, structure, and / or configuration of the cell. The morphology of a cell may comprise one or more aspects of a cell’ s appearance, such as, for example, shape, size, arrangement, form, structure, pattern(s) of one or more internal and / or external parts of the cell, or shade (e.g., color, greyscale, etc.). Non -limiting examples of a shape of a cell may include, but are not limited to, circular, elliptic, dumbbell, star-like, flat, scale-like, columnar, invaginated, having one or more concavely formed walls, having one or more convexly formed walls, prolongated, having appendices, having cilia, having angle(s), having corner(s), etc. A morphological feature of a cell may be visible with treatment of a cell (e.g., small molecule or antibody staining). In other examples, the morphological feature of the cell may not and need not require any treatment to be visualized in an image or video.

[0111] The terms “unstructured” or “unsorted,” as used interchangeably herein, generally refers to a mixture of cells (e.g., an initial mixture of cells) that is not substantially sorted (or rearranged) into separate partitions. An unstructured population of cells may comprise at least two types of cells that can be distinguished by exhibiting different properties (e.g., one or more physical properties, such as one or more different morphological characteristics as disclosed herein). The unstructured population of cells may be a random (or randomized) mixture of the at least two types of cells. The cells as disclosed herein may be viable cells. A viable cell, as disclosed herein, maybe a cell that is not undergoing necrosis or a cell that is not in an early or late apoptotic state. In other examples, the cells may not and need not be viable (e.g., fixed cells).

[0112] IL Example of Cell Analysis System

[0113] The systems and methods described herein may be utilized to analyze a cell and / or sort (or partition) the cell from a population of cells. A cell may be directed through a flow channel, and one or more imaging devices (e.g., sensor(s), camera(s)) may capture one or more images / videos of the cell passing through the flow channel. Subsequently, the image(s) / video(s) of the cell may be analyzed in real-time, such that a decision may be made in real-time (e.g., automatically by the machine learning algorithm) to determine (i) whether to sort the cell or not and / or (ii) which sub -channel of a plurality of sub -channels to sort the cell into.

[0114] FIG. 1 shows an example of a cell analysis system (100), which maybe used to capture images of cells, and apply machine learning or artificial intelligence to analyze the captured images of the cells, and automatically sort the cells based on the analysis. System (100) of this example includes a pump (110) that is operable to drive a sample cell-containing fluid from a reservoir (112) into a cartridge (120). Cartridge (120) may be provided as a modular component, such that cartridge (120) may be readily replaced within system (100) (e.g., to analyze different batches of sample cells, etc.). The remaining components of system (100) that do not get replaced each time cartridge (120) is replaced may be collectively referred to as “the instrument.” The instrument of system (100) may include pump (110); or pump (110) may be considered as a separate component such that a different pump (110) may be used when a different batch of sample cells is being analyzed. Similarly, the instrument of system (100) may include reservoir (112); or reservoir (112) may be considered as a separate component such that a different reservoir (112) maybe used when a different batch of sample cells is being analyzed.

[0115] In some examples, reservoir (112) comprises a syringe barrel; and pump (110) comprises a syringe pump. In other examples, pump (110) may take any other suitable form, including but not limited to a gravity feed, a peristaltic pump, etc. Reservoir (112) may also take any other suitable form, including but not limited to a vial, tube, etc. The sample in reservoir (112) may be prepared by fixation and staining; and may contain viable cells. The fluid in which the sample cells are contained may include an aqueous solution (e.g., water, buffer, saline, etc.), an oil, or any other suitable fluid.

[0116] Cartridge (120) includes a flow channel (122) fluidically coupled with pump (110), such that pump (110) is operable to drive the sample cell-containing fluid from reservoir (112) through flow channel (122). Cartridge (120) may comprise a microfluidic chip, a flow cell, or any other kind of structure through which fluid may flow; and through which cells inthe fluid may be imaged. A light source (130) generates light for such imaging. In particular, an optical assembly (132) directs light from light source (130) toward an imaging region of flow channel (122). In some examples, light source (130) comprises a source of incoherent white light, such as an arc lamp, etc. In other examples, light source (130) may take any other suitable form. Optical assembly (132) may comprise any suitable number and / or arrangement of lenses and / or other elements as will be apparent to those skilled in the art in view of the teachings herein.

[0117] The light from light source (130), as directed by optical assembly (132), illuminates cells as the cells pass through the imaging region of flow channel (122). An objective lens assembly (140) is positioned on the opposite side of the imaging region of flow channel (122), magnifies the images of cells passing through the imaging region of flow channel (122), and directs the magnified images to a camera (142). Objective lens assembly (140) and camera (142) thus cooperate to capture high resolution images of cells that pass through the imaging region of flow channel (122), as illuminated by light source (130) and optical assembly (132). By way of example only, objective lens assembly (140) may provide magnification ranging from approximately 10x to approximately 200*. In other examples, objective lens assembly (140) may provide any other suitable level of magnification. By way of further example only, camera (142) may provide an exposure time ranging from approximately 0.001 ps to approximately 1 ms. In other examples, camera (142) may provide any other suitable exposure time.

[0118] An image processing module (144) receives images from camera (142) and processes those received images in real time. Image processing module (144) may include one or more processors, one or more memories, and various other suitable electrical components. Image processing module (144) may also include software, firmware and / or hardware. In some examples, image processing module (144) is in communication with a remote server and / or with other components. The one or more processors of image processing module (144) may comprise one or more of a programmable processor, a programmable controller, a microprocessor, a microcontroller, a graphics processing unit (GPU), a digital signal processor (DSP), a reduced-instruction set computer (RISC), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a field programmable logic device (FPLD), a logic circuit, and / or another logic-based device executing various functions including the ones described herein.

[0119] Image processing module (144) may utilize any of a number of techniques to classify or otherwise analyze images of cells captured by camera (142). For instance, cellimage data may be analyzed to plot a plurality of cells into a cell clustering map. The image data may comprise tag-free images of single cells. In other examples, the image data may comprise images of single cells that are tagged (e.g., with a heterologous marker). The image data may be processed to generate a cell morphology map. The cell morphology map may comprise a plurality of morphologically distinct clusters corresponding to different types or states of the cells. In some cases, a classifier (e.g., a cell clustering machine learning algorithm or deep learning algorithm) may be trained by using the cell morphology map. The classifier may be configured to classify a cell image sample based on its proximity, correlation, or commonality with one or more of the morphologically distinct clusters. Thus, in some cases, the classifier may be used to classify the sample cell image sample accordingly. This classification may be fully automatic, such that the classification is accomplished solely by software executed through image processing module (1 4), without additional human operator review of the sample cell image. In some other examples, the classification is at least partially manual such that a human operator verifies or otherwise intervenes to inform or approve the classification of the sample cell image.

[0120] Regardless of the technique(s) used by image processing module (144) to classify or otherwise analyze images of cells captured by camera (142), system (100) may provide sorting of cells in cartridge (120) based on such image processing. In some examples, cartridge (120) may include two or more outlet channels from flow channel, and system (100) may automatically activate one or more valves to direct an imaged cell through a selected one of those outlet channels based on the image analysis of the cell by image processing module (144). For instance, a certain outlet channel may be selected if classification or other analysis by image processing module (144) determines that the cell appears to be a certain cell type of interest. In other examples, system (100) may provide cell sortingin any other suitablefashion; and based on any suitable criterion or criteria. In some other examples, system (100) provides imaging and analysis of cells without subsequent sorting of cells. In such examples, the imaged cells may remain contained in cartridge (120) after imaging or may exit cartridge (120) via an outlet port after imaging.

[0121] As noted above, the remaining components of system (100) that do not get replaced each time cartridge (120) is replaced may be collectively referred to as “the instrument.” In some examples, the instrument includes light source (130), optical assembly (132), objective lens assembly (140), camera (142), and various other components that removably receive cartridge (120) and provide any fluidic couplings, etc., that are needed for system (100) to perform properly. The instrument may further include image processingmodule (144). In other examples, image processing module (144) may be provided as a separate component (e.g., computer, etc.) thatis coupled with camera (142) of the instrument to process images captured by camera (142). As further noted above, the instrument may further include or omit either or both of pump (110) and / or reservoir (112).

[0122] IILExample of Cartridge

[0123] FIGS. 2-6 show an example of a form that may be taken by cartridge (120). In particular, FIGS. 2-6 show an example of a cartridge (200) that may be used in system (100) to provide imaging, analysis, and sorting of cells flowed through cartridge (200). Cartridge (200) of this example includes a first lay er (300), a second layer (400), and a third layer (500). In the present example each of layers (300, 400) comprises a polymer (e.g., a siloxane- containing polymer, such as polydimethylsiloxane (PDMS), thermoset plastic, hydrogel, thermoplastic elastomer (TPE), thermoplastic polyurethane (TPU), polycarbonate (PC), polystyrene (PS), poly(methyl methacrylate) (PMMA), cyclic olefin copolymer (COC), etc.). Layer (500) may comprise a glass (e.g., borosilicate or other silicate glass, etc.) or a polymer (e.g., polycarbonate (PC), polystyrene (PS), poly(methyl methacrylate) (PMMA), cyclic olefin copolymer (COC), etc.). In other examples, eachlayer(300, 400, 500)may comprise any other suitable material or combination of materials. Layers (300, 400, 500) are arranged such that a top surface (302) of layer (300) is exposed, a bottom surface (304) of layer (300) is apposed with a top surface (402) of layer (400), and a bottom surface (404) of layer (400) is apposed with a top surface (502) of layer (500). Layer (500) acts as a substrate, providing structural support to layers (300, 400), with a bottom surface (502) of layer (500) being placed upon a mounting surface (not shown) in an instrument of system (100).

[0124] As shown in FIGS. 2-4, layer (300) is substantially thicker than layer (400). As also shown in FIGS. 2-4, layer (300) includes a plurality of fluid input ports (310), a plurality of fluid output ports (312), plurality of pneumatic ports (320), and a plurality of well channels (340), and a pair of tab s (306). Ports (310, 312, 320) are in the f orm of channels f ormed through the entire thickness of layer (300), such that each port (310, 312, 320) is open at top surface (302) and at bottom surface (304). In some examples, fluid input conduits of system (100) are inserted into fluid input ports (310), fluid output conduits of system (100) are inserted into fluid output ports (312), and pneumatic input conduits of system (100) are inserted into pneumatic ports (320). An instrument of system (100) may thus communicate liquids to cartridge (200) via fluid input ports (310), receive liquids from cartridge (200) via fluid output ports (312), and provide pneumatic pressure to cartridge (200) via pneumatic ports (320). In some examples,the conduits of system (100) that are coupled with ports (310, 312, 320) comprise flexible tubes. In other examples, such conduits may take any other suitable form.

[0125] As shown in FIG. 4, bottom surface (304) of layer (300) includes a plurality of pneumatic channels (322), with each pneumatic channel (322) being in fluidic communication with a corresponding pneumatic port (320). Pneumatic channels (322) thus receive pneumatic pressure communicated through pneumatic ports (320). Such pneumatic pressure may be used to provide deflection of regions of layer (400) underlying pneumatic channels (322), such that those regions of layer (400) may be operated as pinch valves to close fluidic communication between layers (400, 500) as described in greater detail below. Each pneumatic channel (322) is formed as a recess in bottom surface (304), such that pneumatic pressure is communicated along the space defined collectively by top surface (402) of layer (400) and each pneumatic channel (322). In other words, top surface (402) of layer (400) defines a bottom of each pneumatic channel (322).

[0126] As shown in FIGS. 2-3 and 5, lay er (400) includes a plurality of fluid input ports (410), a plurality of fluid output ports (412), and a plurality of well openings (440). Ports (410, 412) and well openings (440) are in the form of openings formed through the entire thickness of layer (400). Fluid input ports (410) of layer (400) are positioned to align with fluid input ports (310) of layer (300), such that fluid may be communicated from an instrument of system (100) through layer (400) via fluid input ports (310, 410). Fluid output ports (412) of layer (400) are positioned to align with fluid output ports (312) of layer (300), such that fluid may be communicated through layer (400) to an instrument of system (100) via fluid output ports (312, 412). Well openings (440) of lay er (400) are positioned to align with well channels (340) of layer (300), such that fluid may be communicated through layer (400) via well openings (440) into well channels (340). Well openings (440), well channels (340), and top surface (502) oflayer (500) thus cooperate to define a plurality of wells (750, 752, 754, 756, 758, 760), in which particles in fluid may be stored. In some examples, a removable layer (e.g., tape, film, foil, etc.) or other removable cover is provided over openings (440), such as to minimize, and in some instances even prevent, evaporation from the underlying wells, to minimize, and in some instances even prevent, contamination of the underlying wells, and / or for other reasons. In some such examples, an operator may remove such a layer or cover from a well to retrieve fluid from the well (e.g., via pipette, etc.). It should be understood that layer (400) does not include pneumatic openings or ports in this example, such that pneumatic pressure is not communicated through layer (400).

[0127] As shown in FIG. 5, bottom surface (404) oflayer (400) includes a fluidic testinput region (450), a pair of fluidic flush input regions (460), a pair of fluidic flush output regions (462), a sample fluid receiving region (600), a flowcontrol fluid receiving region (620), a flow drive fluid receiving region (670), and a sample output region (680). A plurality of fluidic channels (442, 452, 464, 604, 662. 664, 672) are formed as recesses in bottom surface (304), such thatfluid is communicated alongthe space defined collectively by top surface (502) of layer (500) and each fluidic channel (442, 452, 464, 604, 662. 664, 672).

[0128] Fluidic channel (452) terminates within layer (400), such that fluidic channel (452) lacks any kind of fluidic outlet. In some scenarios, a fluid input conduit may be coupled with the fluid input port (310) over fluidic test input region (450), and fluid may be communicated into fluidic channel (452) via the fluid input ports (310, 410) over fluidic test input region (450). This may be done to provide a quality control check, to ensure that layers (400, 500) are properly sealed together. In other words, if backpressure quickly accumulates in the fluid input conduit that is coupled with the fluid input port (310) over fluidic test input region (450), such back pressure may indicate that layers (300, 400) are properly sealed together. If such back pressure does not sufficiently accumulate, this may indicate that layers (400, 500)arenotproperly sealed together. It should be understood that similar quality control testing may be performed with pneumatic pressurization through a pneumatic port (320) into a pneumatic channel (322), to ensure that layers (300, 400) are properly sealed together.

[0129] A fluidic channel (464) extends between each fluidic flush input regions (460) and a corresponding fluidic flush output region (462). In some scenarios, a fluid input conduit may be coupled with the fluid input port (310) over fluidic flush input regions (460), and a fluid output conduit may be coupled the fluid output port (312) over fluidic flush output region (462). Fluid may be communicated into flush input region (460) via fluid input ports (310, 410) over fluidic flush input region (460), may flow along fluidic channel (464), then may exit fluidic output region (462) via fluidic output ports (312, 412) over flush output region (462). This may be done to provide flushing of the fluid conduits that are coupled with these ports (310, 412), such as when a cartridge (200) has been replaced, to remove any contaminants that might otherwise be found in those fluid conduits. The combination of a flush input region (460), afluidic channel (464) a flush output region (462), fluid input port (310), and fluid outlet port (312) may be collectively understood to form a flush assembly. In some examples, the fluid communicated through the flush assembly includes a bio -compatible fluid such as an aqueous based buffer fluid or liquid culture medium; or a bio -compatible oil based fluid. In other examples, other kinds of flush fluid may be used.

[0130] A fluidic channel (604) extends from sample fluid receiving region (600) to ajunction (640). A fluid input conduit may be coupled with the fluid input port (310) over sample fluid receiving region (600), and a fluid containing sample cells may be communicated to junction (640) via the fluid input ports (310, 410) over sample fluid receiving regi on (600) and via fluidic channel (604). A pair of fluidic channels (626) extend from flow control fluid receiving region (620) to junction (640), such that fluidic channels (604, 626) converge at junction (640). A fluid input conduit may be coupled with the fluid input port (310) over flow control fluid receiving region (620), and a flow control fluid maybe communicated to junction (640) via the fluid input ports (310, 410) over flow control fluid receiving region (620) and via fluidic channels (626). The fluid from fluidic channels (604, 626) exits junction (640) along a sampling channel (650).

[0131] The fluid communicated along sampling channel (650) may contain sample cells as noted above. These cells may be imaged by the instrument of system (100) as also noted above. Such imaging may be performed as the cells traverse sampling channel (650). For instance, FIG. 6 shows an example of an imagingregion (900) thatmay be positioned along sampling channel (650). In some examples, light source (130) and optical assembly (132) are positioned over cartridge (200) to illuminate imaging region (900); while objective lens assembly (140) and camera (142) are positioned under cartridge (200) to capture images of cells within imaging region (900). Other examples may provide imaging region (900) at any other suitable location or locations along sampling channel (650). Some examples may also provide a plurality of imaging regions (900) at different respective positions along sampling channel (650).

[0132] Sampling channel (650) terminates in anotherjunction (660), which allows fluid to flow from sampling channel to either a first outlet channel (662) or a second outlet channel (664). Each outlet channel (662, 664) maybe selectively opened and closedthrough pneumatic valving. In particular, a pneumatic channel (322) is positioned over each outlet channel (662, 664), in a region just downstream of junction (660), such that pneumatic pressurization within a selected pneumatic channel (332) causes the underlying region of layer (400) to deform downwardly against top surface (502) of layer (500), thereby effectively providing a closed valve in that outlet channel (662, 664). When the pneumatic pressure is relieved in the pneumatic channel (322) over a given outlet channel (662, 664), the underlying region of layer (400) may return to a non-deformed (i.e., flat) state, thereby effectively opening the fluid pathway through that outlet channel (662, 664).

[0133] If the pneumatic valve for outlet channel (662) is opened while the pneumatic valve for outlet channel (664) is closed, the fluid from sampling channel (650) may flowthrough outlet channel (662) via junction (660). The fluid path from outlet channel (662) then continues through a selected fluidic channel (442). Each fluidic channel (442) provides a fluidic communication path between outlet channel (662) and a respective well formed by well openings (440) and well channels (340). The fluid path between outlet channel (662) and each fluidic channel (442) may be selectively opened and closed through pneumatic valving as described above. In particular, a pneumatic channel (322) is positioned over each fluidic channel (442), in a region just downstream of outlet channel (662), such that pneumatic pressurization within a selected pneumatic channel (332) causes the underlying region of layer (400) to deform downwardly against top surface (502) of layer (500), thereby effectively providing a closed valve in that fluidic channel (442). When the pneumatic pressure is relieved in pneumatic channel (322), theunderlying region of layer (400) may return to a non -deformed (i.e., flat) state, thereby effectively opening the fluid pathway through fluidic channel (442).

[0134] In some scenarios, it may be beneficial to provide additional assistance to the flow of fluid from outlet channel (662) through a selected fluidic channel (442) to reach a selected well channel (340) via an underlying well opening (440). To that end, additional fluid may be communicated through a fluid input conduit that is coupled with the fluid input port (310) over flow drive fluid receiving region (670). This additional fluid may reach outlet channel (662) via ports (310, 410) over flow drive fluid receiving region (670) and further via fluidic channel (672). Atthe time this additional fluid is communicated to outlet channel (662), the pneumatic valve between outlet channel (662) and junction (660) may be in a closed state. The additional fluid from flow drive fluid receiving region (670) and fluidic channel (672) may provide a “boost” to fluid in outlet channel (662), thereby further driving the fluid from outlet channel (662) through the selected fluidic channel (442); and ultimately to the selected well channel (340) via an underlying well opening (440). In some examples, the additional boosting fluid provided via flow drive fluid receiving region (670) and fluidic channel (672) may include any bio-compatible fluid, such as liquid culture medium, cell lysis solution, or an oil based fluid. In other examples, other kinds of fluid may be used.

[0135] If the pneumatic valve for outlet channel (664) is opened while the pneumatic valve for outlet channel (662) is closed, the fluid from sampling channel (650) may flow through outlet channel (664) via junction (660). The fluid path from outlet channel (664) reaches sample output region (680). The fluid exits sample output region (680) via the fluid output ports (412, 312) that are positioned over sample output region (680). A fluid output conduit may be coupled with the fluid output port (412) over sample output region (680), such that the fluid may exit cartridge (200) via this fluid output conduit. The fluid output conduitmay be further coupled with a reservoir that is either integrated into the instrument of system (100) or is external to the instrument.

[0136] As noted above, a first set of pneumatic valves may be actuated to allow fluid to flow from sample channel (650) to either outlet channel (662) or outlet channel (664); and if the fluid flows through outlet channel (662); a second set of pneumatic valves may be actuated to allow the fluid to flow through a selected fluidic channel (442) to reach a selected well channel (340) via an underlying well opening (440). System (100) may execute a control algorithm to automatically select which pneumatic valves to activate. This control algorithm may be executed in response to data from image processing module (144). In other words, image processing module (144) may classify or otherwise analyze images of cells captured by camera (142) as the cell-containing fluid passes through imaging region (900), and the pneumaticvalvesdescribedabove may provide sorting of cells in the fluid based on suchimage processing. For instance, cells of a first type (as identified by image processing module (144)) may be routed via pneumatic valving to a first well channel (340), cells of a second type (as identified by image processingmodule (144)) may be routed via pneumatic valvingto a second well channel (340), and cells of a third type (as identified by image processing module (144)) may be routed via pneumatic valving to sample output region (680).

[0137] IV.Example of Flow Control Features of Cartridge

[0138] As noted above, a fluid containing sample cells may be communicated to cartridge (200) via a fluid input conduit that is positioned over sample fluid receiving region (600); while a flow control fluid may be communicated to cartridge (200) via a fluid input conduit that is positioned over flow control fluid receiving region (620). FIG. 7 shows these regions (600, 620) in greater detail. In some examples, the flow control fluid includes a buffer fluid. In some examples the flow control fluid further includes beads; while in other examples the flow control fluid does not include beads. The flow control fluid may include a bio - compatible fluid. In some examples, the flow control fluid has a viscosity that differs from the viscosity of the fluid containing sample cells; while in other examples, the flow control fluid has the same viscosity as the viscosity of the fluid containing sample cells. In some examples, other kinds of fluid may be used for flow control fluid.

[0139] As shown, sample fluid receiving region (600) comprises a teardrop shaped recess in the bottom surface (404) of layer (400), with an array of filtering elements (602) positioned within the teardrop shape. Each filtering element (602) in this example is in the form of a cylindraceous structure that extends down to top surface (502) of layer (500).Filtering elements (602) are spaced apart from each other with enough distance to allow cells to be carried by the cell-containing fluid through the recess of fluid receiving region (600) to fluidic channel (604). However, filtering elements (602) are close enough to each other to filter out any debris thatmay be present in the cell -containing fluid, such that filtering elements (602) may prevent unwanted clogging of fluidic channel (604).

[0140] Flow control fluid receiving region (620) comprises a circle shaped recess in the bottom surface (404) of layer (400), with an array of filtering elements (602) positioned within the circle shape. Filtering elements (622) of flow control fluid receiving region (620) are structurally configured and operable just like filtering elements (602) described above. Filtering elements (622) may thus prevent unwanted clogging of a fluidic channel (624), which provides a pathway from flow control fluid receiving region (620) to fluidic channels (626). As shown in FIG. 7, fluidic channels (626) include a first fluidic channel (626a) and a second fluidic channel (626b), which have mirror symmetry with each other. Each fluidic channel (626) has a serpentine configuration with a herringbone region (630) and an outlet region (638) leading to junction (640).

[0141] While sample fluid receiving region (600) and flow control fluid receiving region (620) are described above as including filtering elements (602, 622), other portions of cartridge (200) may also include filtering elements like filtering elements (602, 622). For instance, fluidic test input region (450), flush input regions (460), flush output regions (462), flow drive fluid receiving region (670), and / or sample output region (680) may each include filtering elements like filtering elements (602, 622).

[0142] In some examples, it may be desirable to carefully control the fluid flow dynamics within sampling channel (650) during operation of system (100) with cartridge (200). Controlling the fluid flow dynamics within sampling channel (650) may ensure that the cells in in the fluid communicated along sampling channel (650) have a desired spacing relative to each other and / or relative to the three-dimensional confines of sampling channel (650). Providing such control over the spacing of the cells relative to each other and / or relative to the three-dimensional confines of sampling channel (650) may optimize the imaging of the cells within imaging region (900), which may in turn optimize the processing of the cell images and the results obtained through such image processing. The following description provides examples of howthe fluid flow dynamics within sampling channel (650) may be controlled.A. Example of Three-Dimensional Flow Focusing Feature in Junction

[0143] Flow focusing is a concept in fluid dynamics where a focusing fluid or sheath fluid is used to control the flow of another fluid, which may be referred to as a core fluid or afocused fluid. Flow focusing may be achieved along one or more dimensions in sp ace. Flow focusing may be inertial and / or hydrodynamic. In the context of sampling channel (650), flow focusingmay be used to position the cells in the fluid receivedvia sample fluid receivingregion (600) within a certain desired region of the cross-sectional space of sampling channel (650), which may facilitate imaging of those cells by providing a consistent and predicable focal plane that does not require movement or refocusing of camera (142) and / or objective lens assembly (140), etc. Thus, the fluid received via sample fluid receiving region (600) may constitute the core fluid or the focused fluid; while the fluid received via flow control fluid receiving region (620) may constitute the focusing fluid or sheath fluid.

[0144] The flow focusing in sampling channel (650) may be achieved through the structural configuration of junction (640). As shown in FIGS. 29-31 , junction (640) includes an expanded recess (642), which extends along a portion of the length of each outlet region (638) of each fluidic channel (626). Each outlet region (638) and fluidic channel (604) have the same first width (Wl). Each outlet region (638) and fluidic channel (604) also have the same first height (Hl) with respect to top surface (502) of layer (500). Expanded recess (642) includes sidewalls (646) that define a second width (W2) and a length (L). Expanded recess (642) defines second height (H2) between a ceiling (644) of expanded recess (642) and top surface (502) of layer (500).

[0145] The length (L) of expanded recess (642) is greater than the width (W2) of expanded recess (642), such that expanded recess (642) has a rectangular configuration in this example. The width (W2) of expanded recess (642) is slightly smaller than the width (Wl) of outlet region (638) and fluidic channel (604), though widths (Wl, W2) may be equal in some other examples. In some examples, each width (Wl, W2) is approximately 50 pm. The length (L) of expanded recess (642) is substantially greater than the width (Wl ) of outlet region (638) and fluidic channel (604). In some examples, the length (L) is approximately 300 pm. The height (H2) of expanded recess (642) is also substantially greater than the height (Hl) of outlet region (638) and fluidic channel (604). In some examples, the height (H2) of expanded recess (642) ranges from approximately 50 pm to approximately 60 pm; while the height (Hl) of outlet region (638) is approximately 22 pm. In some examples, the length (L) of expanded recess (642) ranges from approximately 4 times the width (W2) of expanded recess (642) to approximately 20 times the width (W2) of expanded recess (642). In some examples, the length (L) of expanded recess (642) ranges from approximately 4 times the width (Wl) of outlet region (638) to approximately 20 times the width (Wl) of outlet region (638). In some examples, the height (H2) of expanded recess (642) ranges from approximately 2 times theheight (Hl ) of outlet region (638) and fluidic channel (604) to approximately 4 times the height (Hl) of outlet region (638) and fluidic channel (604). The specific dimensions and ratios provided above are not intended to be limiting. Other dimensions and ratios may be used.

[0146] FIGS. 32-35 show an example of flow focusing fluid dynamics that may be achieved by expanded recess (642) at junction (640). As can be seen, fluid enters junction (640) from outlet regions (638) of fluidic channels (626) in opposing directions along the y - dimension; while fluid enters junction (640) from fluidic channel (604) along the x -dimension. The opposing flow of fluid from fluidic channels (626) along the y -dimension thus drives the cells in the fluid of fluidic channel (604) inwardly along the y -dimension, toward the central region of junction (640). This aspect of the flow is best seen in FIGS. 33 and 35. The fluid from fluidic channels (626) also flows upwardly along the z-dimension into expanded recess (642), asbest seen in FIG. 11 . The flow of fluid from fluidic channels (626) in expandedrecess (642) is turbulent, with sidewalls (646) and ceiling (644) causingthe fluid from fluidic channels (626) to flow back downwardly along the z-dimension. This downward flowfurther drives the cells in the fluid of fluidic channel (604) downwardly alongthe z-dimension, as best seen in FIGS. 34 and 35.

[0147] Thus, as the cell-containing fluid flows along sampling channel (650) downstream of junction (640), the cells in the cell -containing fluid may be substantially confined within the z-dimension (alongthe bottom of sampling channel (650)) and within the y-dimension (alongthe center of sampling channel (650)). Moreover, this flow focusing may be maintained along the length of sampling channel (650), including within imaging region (800), through the inertial focusing phenomenon. This may be achieved in a flow having a Reynolds numberthatis approximately 2.5, which may be achieved when the flow rate through fluidic channel (604) is approximately 1 pL / min, the flow rate through each outlet region (638) of each fluidic channel (626) is approximately 9 pL / min, and the flow rate through sampling channel (650) is approximately 10 pL / min.

[0148] While expanded recess (642) is provided in the upper region of junction (640) in this example, some variations of cartridge (200) may instead position expanded recess (642) in the lower region of junction (640). Such repositioning of expanded recess (642) may tend to focus the cells in the upper region of sampling channel (650) rather than the lower region of sampling channel (650).

[0149] As another example, a cartridge (200) may include two or more expanded recesses (642), from the same side or from different sides of sampling channel (650). An example of such a configuration is shown in FIG. 29A. In this example, a fluidic channel(1604) is structurally configured and operable like fluidic channel (604) described above; while a set of fluidic channels (1638, 1738) are structurally configured and operable like fluidic channels (626) described above. Fluidic channels (1604, 1638) converge at a junction (1640) which is structurally configured and operable like junction (640) described above. Junction (1640) of this example thus includes an expanded recess (1642), which is structurally configured and operable like expanded recess (642) described above. The fluid output from junction (1640) is conveyed along another fluidic channel (1651), which converges with fluidic channels (1738) at another junction (1740). A sampling channel (1650) provides a fluid output from junction (1740). Sampling channel (1650) may be configured and operable like sampling channel (650) described above.

[0150] Junction (1740) of this example includes an expanded recess (1742) that is structurally configured and operable similar to expanded recess (1642), though expanded recess (1742) extends below the plane of fluidic channels (1604, 1638, 1651, 1738) alongthe z-dimension (whereas expanded recess (1642) extends above the plane of fluidic channels (1604, 1638, 1651, 1738) along the z-dimension). Thus, to the extent that expanded recess (1642) may tend to focus the flow of fluid downwardly alongthe z-dimension; expanded recess (1742) may tend to focus the flow of fluid upwardly alongthe z-dimension. In addition, the combination of recesses (1642, 1742) may tend to focus the flow along an x-y plane that is substantially centered along the z-dimension in sampling channel (1650). While recess (1742) is positioned downstream of recess (1642) in this example, other examples may provide recess (1642) downstream of recess (1742).B. Examples of Mixing Structures in Side Channels Upstream of Junction

[0151] In some examples, it may be desirable to perform a calibration of camera (142) and objective lens assembly (140) before capturing images of cells in imaging region (900). In some of those examples, it may be desirable to communicate beads (or other particles) having a known structural configuration along sampling channel (650), such that camera (142) may capture images of the beads as they pass through imaging region (900) during a calibration routine. In some examples, such beads (or other particles) may also be communicated along sampling channel (650) while sample cells (or other sample particles) are also communicated along sampling channel (650). The presence ofthe beads in sampling channel (650) may allow image processing module (144) to detect changes in the structural configuration of sampling channel (650) during operation of system (100), such as expansion of sampling channel (650) caused by thermal expansion of cartridge (200) during operation of system (100). In some suchexamples, such changes in the structural configuration of sampling channel (650) during operation of system (100) may be detected due to a tendency of beads to flow along separate x-y planes that are separated from each other along the z-dimension by a distance that varies with the structural configuration of sampling channel (650).

[0152] In some cases where beads are used, it may be beneficial to communicate those beads through fluidic channels (626). Those beads may tend to arrange themselves within the fluid flowing along fluidic channels (626) in a predictable arrangement. Even though it may be desirable to have a predictable arrangement of particles (e.g., cells) as those particles travel along sampling channel (650) in some examples, it may be desirable for particles to have an unpredictable arrangementbeforeenteringjunction (640) in some examples. An unpredictable arrangement of particles upstream of junction (640) may in fact lead to a more predictable arrangement of particles downstream of junction (640). It may therefore be desirable in some examples to provide a feature in fluidic channels (626) that will add chaos to the arrangement of beads in fluid that flows through fluidic channels (626).

[0153] As noted above, each fluidic channel (626) includes a herringboneregion (630).FIGS. 8-10 show herringbone region (630) in greater detail. Herringbone region (630) serves as a mixing feature and thus provides chaos to the arrangement of beads in fluid that flows through herringbone region (630). Each herringbone region (630) includes a plurality of chevron shaped recesses (634) above the flow channel (632) through herringbone region (630). Each recess (634) includes a ceiling (634) and set of sidewalls (636). In some examples, as shown in FIG. 10, sidewalls (636) define a length (L2) of approximately 60 pm. Sidewalls (636) may also form angles (0) with each other at approximately 45 degrees. Ceiling (634) may be positioned at a height (H3) of approximately 33 pm relative to the bottom of each sidewall (636). The specific dimensions provided above are not intended to be limiting. Other dimensions may be used.

[0154] FIG. 11 A shows an example of an arrangementof beads (652) in fluidicchannel (626) upstream of herringbone region (630); while FIG. 11B shows an example of an arrangement of beads (652) in fluidic channel (660) in outlet region (638) of fluidic channel (626) downstream of herringbone region (630). As shown, the arrangement of beads (652) upstream of herringbone region (630) is substantially orderly; whereas the arrangement of beads (652) downstream of herringbone region (630) is substantially stochastic or randomized. This stochastic or randomized arrangement of beads (652) in outlet region (638) may provide a greater likelihood thatbeads (652) will be subjectto the flow focusingphenomenon described below (and achieve an arrangement like that shown in FIG. 15B) than might otherwise beachieved in the absence of herringbone region (630). In other words, without herringbone region (630), beads (652) may be less likely to mimic the arrangement in imaging region (900) that would be achieved by cells later passing through imaging region (900). Herringbone region (630) may thus facilitate replication of cell arrangements in imaging region (900) by bead (660) arrangements in imaging region (900) during calibration of system (100).

[0155] While FIG. 7 shows each fluidic channel (626) having only one herringbone region (630), each fluidic channel (626) may have two or more herringbone regions (630) in other examples. Some other examples may omit herringbone regions (630).C. Examples of Flow Resistance Relationships in Channels of Junction

[0156] In some examples, it may be desirable to maximize the stability of the flow rate of fluid along the entire length of sampling channel (650). For instance, in cases where pneumatic valves are actuated downstream of junction (660) to sort cells in response to image analysis of the cells as they pass through imaging region (900), a stable flow rate of fluid will ensure that the cells are sorted as intended. In other words, a stable flow rate through sampling channel (650) may ensure appropriate synchronization between valve timing and image capture / analysis. The inclusion of flow focusing features such as those described below may tend to complicate the achievement of a stable flow rate through sampling channel (650).

[0157] It may also be desirable in some examples to allow the flow rate of fluid being input through fluid input port (410) of sample fluid receiving region (600), and to allow the flow rate of fluid being input through fluid input port ( 10) of flow control fluid receiving region (620) to be adjusted, while still providing a stable flow rate through sampling channel (650). Allowing greater flexibility in input fluid flow rates may increase the versatility of cartridge (200), such as by allowing end users to meet different fluid flow requirements based on the process protocols at hand.

[0158] The above-described results may be achieved by providing tuned flow resistance through fluidic channels (604, 626, 650) as described below. In particular, the stability of flow along sampling channel (650) is provided or promoted, in part, through precise control of the flow rate of fluid entering junction (640). In turn, the control of the flow rate of fluid entering junction (640) is provided, in part, by providing tuned flow resistance through fluidic channel (604) and each outlet region (638) of each fluidic channel (626). By tuning the flow resistance through fluidic channel (604) and each outlet region (638) of each fluidic channel (626), cartridge (200) may accommodate different flow rates of fluid received via sample fluid receiving region (600) and flow control fluid receiving region (620), while stillmaintaininga certain flowrate ratio through fluidic channel (604) and each outletregion (638). This may allow cartridge (200) to accommodate different end user needs, which may include different flow rates and driving pressures through sample fluid receiving region (600) and flow control fluid receiving region (620).

[0159] The pressure of sample-carrying fluid communicated through fluidic channel (604) may be expressed as “Pl the flow resistance of fluidic channel (604) may be expressed as “Rl,” and the flow rate through fluidic channel (604) may be expressed as “II .” The pressure of flow control fluid communicated through each fluidic channel (626) may be expressed as “P2,” the flow resistance of each fluidic channel (626) may be expressed as “R2 and the flow rate through each fluidic channel (626) may be expressed as “12.” The pressure of the combined fluid communicated through sampling channel (650) may be expressed as “P0,” the flow resistance of sampling channel (650) may be expressed as “R0 and the flow rate through sampling channel (650) may be expressed as “10.” With these parameters identified, a ratio of the flow rate II of fluidic channel (604) to the flow rate 12 of each fluidic channel (626) may be expressed in the following equation (I):

[0160] The flow rate Ioof sampling channel (650) may be expressed in the following equation (II):

[0161] One or more pumps (110) and / or other components may be operated to drive the fluids through fluidic channels (604, 626, 650) may achieve a desired main flow rate Ioin sampling channel (650), and ratio of flow rates Ii / I2of fluidic channels (604, 626), based on the two equations (I, II) above. As can be seen above, these equations (I, II) factor in the flow resistance values R}, R2, Ro of fluidic channels (604, 626, 650). The outcomes of these equations (I, II) may thus be influenced by how fluidic channels (604, 626, 650) are structurally configured to tune the flow resistance value / ?;, R2, Ro of each fluidic channel (604, 626, 650), since the flow resistance value / ?;, R2, Roof each fluidic channel (604, 626, 650) may be fixed by the structural configuration of each fluidic channel (604, 626, 650).

[0162] In the present example, channels (604, 626, 650) are structurally configured such that the flow resistance / ?; of fluidic channel (604) is substantially lower than the flow resistances / ?^ 7?0of channels (626, 650); and such that the flow resistance R2of each fluidicchannel (626) is substantially equal to (or on the same order as) the flow resistance Roof sampling channel (650). This relationship may thus be expressed in in the following equation (III):(Hi) R± « R2 ~ o

[0163] By way of example only, the value of flow resistance R}of fluidic channel (604) may range from approximately 1 / 5 of the value of the flow resistance 7?oof sampling channel (650) to approximately ’ of the value of the flow resistance Ro of sampling channel (650). Similarly, the value of flow resistance R}of fluidic channel (604) may range from approximately 1 / 5 of the value of the flow resistance R2of each fluidic channel (626) to approximately / i of the value of the flow resistance R2of each fluidic channel (626).

[0164] Channels (604, 626, 650) may be structurally configured such that the flow resistance R2of fluidic channel (604) is substantially lower than the flow resistances R2, Rooi channels (626, 650) by fluidic channel (604) having a substantially shorter length than the length of channels (626, 650). Similarly, channels (604, 626, 650) may be structurally configured such that the flow resistance S of each fluidic channel (626) is substantially equal to (or on the same order as) the flow resistance Roof sampling channel (650) by each fluidic channel (626) having a length that is substantially equal to (or on the same order as) the length of sampling channel (650). To achieve substantially equal length of each fluidic channel (626) and sampling channel (650) without creating unnecessary overall length in cartridge (200), each fluidic channel (626) has a serpentine configuration. In some examples, the different flow resistances R2, R2, Romay be achieved by using different cross-sectional areas (e.g., different heights and / or widths) among channels (604, 626, 650).

[0165] With the relationships between R R2, Roprovided as expressed in equation (III), the ratio of the flow rate I] of each fluidic channel (626) to the flow rate I2of fluidic channel (604) may be simplified as the following equation (IV):

[0166] Similarly, with the relationships between R}, R2, Roas expressed in equation (III), the flow rate Io of sampling channel (650) may simplified as the following equation (IV):

[0167] The substantially lower flow resistance R}of fluidic channel (604) may be due, at least in part, to fluidic channel (604) having a substantially shorter length than the lengths of channels (626, 650). In some examples, the flow resistance R2of each fluidic channel (626)ranges from approximately 10 times the flow resistance R] of fluidic channel (604) to approximately 50 times the flow resistance R}of fluidic channel (604); or more particularly, may be approximately 20 times the flow resistance R}of fluidic channel (604). In some examples, the flow resistance 7?oof sampling channel (650) ranges from being approximately equal to the flow resistance R2 of each fluidic channel (626) to being approximately 5 times the flow resistance / ? of each fluidic channel (626); or more particularly, may be approximately 3 times the flow resistance R2 of each fluidic channel (626).

[0168] Minimizing the flow resistance Rj of fluidic channel (604) may minimize the fluid pressure P}applied through sample fluid receiving region (600) and fluidic channel (604), which may in turn minimize the risk of damage to cells contained in the fluid that is communicated through sample fluid receiving region (600) and fluidic channel (604). Having a higher pressure of fluid in fluidic channels (626) (e.g., due to the substantially higher flow resistance of fluidic channels (626)) may not be problematic since the fluid communicated through flow control fluid receiving region (620) and fluidic channels (626) does not contain cells that might otherwise be damaged. Thus, in some examples of operation, the pressure P2of fluid in fluidic channels (626) is set to be higher than the pressure P}of fluid in fluidic channel (604). In addition, to provide positive inflow from fluidic channel (604) into junction (640), the pressure P2of fluid in fluidic channels (626) and the pressure P}of fluid in fluidic channel (604) may be controlled to adhere to the following equation (V):D. Examples of Vertical Flow Focusing Features

[0169] Flow focusing is a concept in fluid dynamics where a focusing fluid or sheath fluid is used to control the flow of another fluid, which may be referred to as a core fluid or a focused fluid. Flow focusing may be achieved along one or more dimensions in space. Flow focusing may be inertial and / or hydrodynamic. In the context of sampling channel (650), flow focusingmay be used to position the cells in the fluid received via sample fluid receiving region (600) within a certain desired region of the cross-sectional space of sampling channel (650), which may facilitate imaging of those cells by providing a consistent and predicable focal plane that does not require movement or refocusing of camera (142) and / or objective lens assembly (140), etc. Thus, the fluid received via sample fluid receiving region (600) may constitute the core fluid or the focused fluid; while the fluid received via flow control fluid receiving region (620) may constitute the focusing fluid or sheath fluid.

[0170] FIG. 12 shows an example of another fluid input region that may be incorporated into cartridge (200) in place of the fluid input region depicted in FIG. 7 to provide a vertical flow focusing feature. Except for the integration of the fluid input region of FIG. 12 instead of the fluid input region of FIG. 7, such a modified example of cartridge (200) may be otherwise structurally configured and operable as descried above. The fluid input region of this example includes a sample fluid receiving region (710), a horizontal flow control fluid receiving region (720), a vertical flow control fluid receiving region (730), and a plurality of fluidic channels (712, 722, 732, 742, 752). Each fluid receiving region (710, 720, 730) includes a recess in the bottom surface (404) of lay er (400), with an array of filtering elements positioned within the recess, as described above with respect to fluid receiving regions (600, 620). Similarly, each fluid receiving region (710, 720, 730) receives fluid via a corresponding fluid input port (310) through layer (300); and via a corresponding fluid input port (410) through layer(400). Each fluidic channel (712, 722, 732, 742, 752) is also defined as a recess in bottom surface (404), such that fluid is communicated along the space defined collectively by top surface (502) of layer (500) and each fluidic channel (712, 722, 732, 742, 752).

[0171] A fluidic channel (712) extends from sample fluid receiving region (710) to a first junction (740), such that a fluid containing sample cells may be communicated to first junction (740) via the fluid input ports (310, 410) over sample fluid receiving region (710) and via fluidic channel (712). A pair of fluidic channels (732) extend from vertical flow control fluid receiving region (730) to first junction (740), such that fluidic channels (712, 732) converge at first junction (740). A fluid input conduit may be coupled with the fluid input port (310) over vertical flow control fluid receiving region (730), and a vertical flow control fluid may be communicated to first junction (740) via the fluid input ports (310, 410) over vertical flow control fluid receiving region (730) and via fluidic channels (732). The fluid from fluidic channels (712, 732) exits first junction (740) along an intermediate fluidic channel (742).

[0172] Intermediate fluidic channel (742) extends to a second junction (750), such that the combined flow from fluidic channels (712, 732) may enter second junction (750) via intermediate fluidic channel (742). A pair of fluidic channels (722) extend from horizontal flow control fluid receiving region (720) to second junction (750), such that fluidic channels (742, 722) converge at junction (740). A fluid input conduit may be coupled with the fluid input port (310) over horizontal flow control fluid receiving region (720), and a horizontal flow control fluid may be communicatedto second junction (750) via the fluid inputports (310, 410) over horizontal flow control fluid receiving region (720) and via fluidic channels (722). As shown in FIG. 12, each fluidic channel (722) has a serpentine configuration similar to fluidicchannels (626). While not shown in FIG. 12, each fluidic channel (722) may also include a herringbone region like herringbone region (630); or some other kind of mixing feature that provides chaos to the arrangement of particles (e.g., beads, etc.) that may flow through fluid channel (722).

[0173] The fluid from fluidic channels (722, 742) exits second junction (752) along a sampling channel (752). The fluid communicated along sampling channel (752) may contain sample cells as noted above. These cells may be imaged by the instrument of system (100) as also noted above. Such imaging may be performed as the cells traverse an imaging region along sampling channel (752). Such an imaging region along sampling channel (752) may be analogous to imaging region (900) described above.

[0174] The below description provides various examples of structures that may be used to provide flow focusing in a vertical direction (i.e., along the z-dimension) in fluid flowing through intermediate fluidic channel (742). As described below, these vertical flow focusing structures may be provided at first junction (740); or may at least partially form first junction (740). While first junction (740) and the below described vertical flow focusing structures are provided upstream of second junction (750), other examples may providejunction (740) and the below described vertical flow focusing structures downstream of second junction (750).

[0175] In addition to the vertical flow focusingfeatures describedbelow, the fluidinput region of FIG. 12 may provide tuned flow resistance as described above with respect to the fluid input region of FIG. 7. For instance, channels (712, 732, 752) may be configured such that the flow resistance of fluidic channel (712) is substantially lower than the flow resistance of channels (732, ,752); and such that the flow resistance of each fluidic channel (732) is substantially equal to (or on the same order as) the flow resistance of sampling channel (752). In some examples, channels (712, 722, 752) may be configured such that the flow resistance of fluidic channel (712) is substantially lower than the flow resistance of channels (722, 752); and such thatthe flow resistance of each fluidic channel (722) is substantially equal to (or on the same order as) the flow resistance of sampling channel (752). In some examples, the flow resistance of fluidic channel (742) is approximately equal to the flow resistance of fluidic channel (712).

[0176] A. First Example of Vertical Flow Focusing Feature at JunctionBetween Channels

[0177] FIS. 13-14 show a first example of a vertical flow focusing feature (800) that may be included in the fluid input region of FIG. 12, at junction (740). Flow focusing feature(800) of this example is in the form of a cylindrical passageway, having a diameter (DI) along the x-y plane that is larger than the width (Wl) of channels (712, 742) along the y -dimension. By way of example only, the diameter (DI) may range from approximately 50 pm to approximately 400 pm; or may be approximately 100 pm. In other examples, the diameter (DI) may have any other suitable value. The cylindrical passageway of flow focusing feature (800) extends along the z-dimension above the x-y plane of channels (712, 742). In some examples, the cylindrical passageway of flow focusing feature (800) is defined as a recess in the bottom surface (404) of layer (400).

[0178] While one fluidic channel (732a) of fluidic channels (732) is shown in FIG. 13, both fluidic channels (732) are intentionally omitted from FIG. 14 for clarity. While both fluidic channels (732) feed into flow focusing feature (800) along the y -dimension (in respective directions facing toward each other) in this example, there may be other variations where vertical flow focusing feature (800) is fed by only one channel providing vertical flow focusingfluid. In such variations, such single channel may providevertical flow focusing fluid to vertical flow focusing feature (800) along the x-dimension, along the z-dimension, or in any suitable direction. As yet another example, a fluid input port (310) and opening (410) may be positioned directly over flow focusing feature (800), or may collectively define flow focusing feature (800), such that there are no fluidic channels (732) feeding into flow focusing feature (800).

[0179] Fluid containing sample cells flows through fluidic channel (712) along the x- dimension. As shown in FIG. 15 A, this may provide a relatively even distribution of sample cells (760) along the y-z plane within fluidic channel (712). Vertical flow focusing fluid flows through flow focusing feature (800) along the z-dimension, such that when the vertical flow focusing fluid enters junction (740) via flow focusing feature (800), the vertical flow focusing fluid bears downwardly along the flow of fluid containing sample cells (760). Thus, as the combined fluid exits junction (740) and continues along intermediate fluidic channel (742), sample cells (760) are substantially confined to the lower half of the z -y plane as shown in FIG. 15B. This arrangement of sample cells (760) may persist along the length of intermediate fluidic channel (742).

[0180] As the combined fluid continues from intermediate fluidic channel (742) through second junction (750), a horizontal flow control fluid enters second junction (750) via channels (722) in opposing directions along the y -dimensions. Since these flow directions from channels (722) face each other, the horizontal flow control fluid may bear inwardly along the y-dimension on the combined flow of the fluid containing sample cells and the vertical flowcontrol fluid. Thus, as the further combined fluid (now including sample-carrying fluid, the vertical flow control fluid, and the horizontal flow control fluid) exits junction (750) and continues along sample channel (752), sample cells (760) may be substantially confined to the central region of sample channel (752) along the y-dimension while also being substantially confined to the lower region of sample channel (752) alongthe z-dimension. This substantial confinement of the positions of sample cells (760) within the y-z plane may persist as sample cells (760) continue along the full length of sample channel (752) in the x-direction. In addition, this sub stantial confinement of the positions of sample cells (760) within the y -z plane as sample cells (760) pass through imaging region (900) may promote consistently reliable imaging of sample cells (760).

[0181] As noted above, there maybe some variations where flow focusing alongthe z- dimension by flow focusing feature (800) occurs after flow focusing alongthe y-dimension. In other words, flow focusing feature (800) may be positioned downstream of second junction (750) in some variations. Moreover, some variations may omit a horizontal flow focusing (alongthe y-dimension) aspect, such that only vertical flow focusing (alongthe z-dimension) is provided.

[0182] B. Second Example of Vertical Flow Focusing Feature at JunctionBetween Channels

[0183] FIGS. 16-17 show a second example of a vertical flow focusing feature (810) that may be included in a variation of fluid input region (710) of FIG. 12 where fluidic channel (712) is omitted. Flow focusing feature (810) is positioned within the tapered region of the teardrop shape of fluid input region (710). Flow focusing feature (810) of this example is in the form of a cylindrical passageway, having a diameter (DI) alongthe x-y plane thatis larger than the width (Wl) of channel (742) along the y-dimension. By way of example only, the diameter (DI) may range from approximately 50 pm to approximately 400 pm; or may be approximately 100 pm. In other examples, the diameter (DI) may have any other suitable value. The cylindrical passageway of flow focusing feature (810) extends along the z- dimension above the x-y plane of channels (712, 742). In some examples, the cylindrical passageway of flow focusing feature (810) is defined as a recess in the bottom surface (404) of layer (400).

[0184] While one fluidic channel (732a) of fluidic channels (732) is shown in FIG. 16, both fluidic channels (732) are intentionally omitted from FIG. 17 for clarity. While both fluidic channels (732) feed into flow focusing feature (810) along the y-dimension (inrespective directions facing toward each other) in this example, there may be other variations where vertical flow focusing feature (810) is fed by only one channel providing vertical flow focusingfluid. In such variations, such single channel may providevertical flow focusing fluid to vertical flow focusing feature (810) along the x-dimension, along the z-dimension, or in any suitable direction. As yet another example, a fluid input port (310) and opening (410) may be positioned directly over flow focusing feature (810), or may collectively define flow focusing feature (800), such that there are no fluidic channels (732) feeding into flow focusing feature (810).

[0185] As shown in FIGS. 16-17, flow focusing feature (810) is positioned directly at the end of sample fluid receiving region (710), such that the arrangement of flow focusing feature (810), sample fluid receiving region (710), an intermediate fluidic channel (742) converge at a junction (744) that is different from junction (740) described above . Fluid containing sample cells flows through sample fluid receiving region (710) generally in the x- dimension, though the flow of the fluid may also have a component in the y-dimension as the fluid enters junction (744). Irrespective of the relationship between the component of the flow along the x-dimension and the component of the flow along the y-dimension as the fluid enters junction (744), the flow may provide a relatively even distribution of sample cells along the y- z plane as the flow enters junction (744), similar to the distribution shown in FIG. 15 A.

[0186] Vertical flow focusing fluid flows through flow focusing feature (810) along the z-dimension, such that when the vertical flow focusing fluid enters junction (744) via flow focusing feature (810), the vertical flow focusing fluid bears downwardly along the flow of fluid containing sample cells. Thus, as the combined fluid exits junction (744) and continues along intermediate fluidic channel (742), the sample cells are substantially confined to the lower half of the z-y plane, as in the arrangement shown in FIG. 15B. This arrangement of sample cells may persist along the length of intermediate fluidic channel (742). The same horizontal flow focusing effects, and confinement of sample cells within the y-z plane as the sample cells pass through imaging region (900), described above in the context of fluid flow downstream of flow focusing feature (800) of FIGS. 13 -14 may also apply to the present context of flow focusing feature (810) of FIGS. 16-17.

[0187] As noted above, there maybe some variations where flow focusing along the z- dimension by flow focusing feature (810) occurs after flow focusing along the y-dimension. In other words, flow focusing feature (810) may be positioned downstream of second junction (750) in some variations. Moreover, some variations may omit a horizontal flow focusing (along the y-dimension) aspect, such that only vertical flow focusing (along the z-dimension)is provided.

[0188] C. Third Example of Vertical Flow Focusing Feature at JunctionBetween Channels

[0189] FIGS. 18-19 show a third example of a vertical flow focusing feature (820) that may be included in the fluid inputregion ofFIG. 12, atjunction (740). Flow focusing feature (820) of this example includes a circular recess (822) and a cylindrical passageway (824). In some examples, circular recess (822) and cylindrical passageway (824) are each defined as a recess in the bottom surface (404) of layer (400). Circular recess (822) is positioned along the same x-y plane as channels (712, 742), while cylindrical passageway (824) is positioned above circular recess (822) along the z-dimension. In some examples, cylindrical passageway (824) and circular recess (822) are coaxially aligned along the same z-axis. In some other examples, circular recess (822) are each centered along respective axes that are offset from each other along the x-y plane. Cylindrical passageway (824) has a diameter (DI) along the x-y plane that is larger than the width (Wl) of channel (742) along the y -dimension. By way of example only, the diameter (DI) may range from approximately 50 pm to approximately 400 pm; or may be approximately 100 pm. In other examples, the diameter (DI) may have any other suitable value. Circular recess (822) has a diameter (D2) along the x-y plane that is larger than the diameter (DI) of cylindrical passageway (824).

[0190] While one fluidic channel (732a) of fluidic channels (732) is shown in FIG. 18, both fluidic channels (732) are intentionally omitted from FIG. 19 for clarity. While both fluidic channels (732) feed into flow focusing feature (820) along the y-dimension (in respective directions facing toward each other) in this example, there may be other variations where vertical flow focusing feature (820) is fed by only one channel providing vertical flow focusingfluid. In such variations, such single channel may providevertical flow focusing fluid to vertical flow focusing feature (820) along the x-dimension, along the z-dimension, or in any suitable direction. As yet another example, a fluid input port (310) and opening (410) may be positioned directly over flow focusing feature (820), or may collectively define flow focusing feature (820), such that there are no fluidic channels (732) feeding into flow focusing feature (820).

[0191] Fluid containing sample cells may enter junction (740) via fluidic channel (712) havingwith a relatively even distribution of sample cells alongthey-z plane as de scribed above with reference to FIG. 15 A. Vertical flow focusing fluid flows through flow focusing feature (820) along the z-dimension, such that when the vertical flow focusing fluid enters junction(740) via flow focusing feature (820), the vertical flow focusing fluid bears downwardly along the flow of fluid containing sample cells. Thus, as the combined fluid exits junction (740) and continues along intermediate fluidic channel (742), the sample cells are substantially confined to the lower half of the z-y plane as described above with reference to FIG. 15B. This arrangement of sample cells may persist along the length of intermediate fluidic channel (742). The same horizontal flow focusing effects, and confinement of sample cells within the y-z plane as the sample cells pass through imaging region (900), described above in the context of fluid flow downstream of flow focusing feature (800) of FIGS. 13 -14 may also apply to the present context of flow focusing feature (820) of FIGS. 18-19.

[0192] As noted above, there maybe some variations where flow focusing along the z- dimension by flow focusing feature (820) occurs after flow focusing along the y-dimension. In other words, flow focusing feature (820) may be positioned downstream of second junction (750) in some variations. Moreover, some variations may omit a horizontal flow focusing (alongthe y-dimension) aspect, such that only vertical flow focusing (alongthe z-dimension) is provided.

[0193] D. Fourth Example of Vertical Flow Focusing Feature at JunctionBetween Channels

[0194] FIGS. 20-21 show a fourth example of a vertical flow focusing feature (830) that may be included in another variation of fluid input region (710) of FIG. 12 where fluidic channel (712) is omitted. Flow focusing feature (830) is positioned within the tapered region of the teardrop shape of fluid input region (710). Flow focusing feature (830) of this example includes a circular recess (832) and a cylindrical passageway (834). Circular recess (832) is positioned alongthe same x-y plane as channel (742) and sample fluid receiving region (710), while cylindrical passageway (834) is positioned above circular recess (832) along the z- dimension. Cylindrical passageway (834) has a diameter (DI) alongthe x -y plane that is larger than the width (Wl) of channel (742) along the y-dimension. By way of example only, the diameter (DI) may range from approximately 50 pm to approximately 400 pm; or may be approximately 100 pm. In other examples, the diameter (DI) may have any other suitable value. Circular recess (832) has a diameter (D2) along the x-y plane that is larger than the diameter (DI) of cylindrical passageway (834). In some examples, circular recess (832) and cylindrical passageway (834) are each defined as a recess in the bottom surface (404) of layer (400).

[0195] While one fluidic channel (732a) of fluidic channels (732) is shown in FIG. 20,both fluidic channels (732) are intentionally omitted from FIG. 21 for clarity. While both fluidic channels (732) feed into flow focusing feature (830) along the y-dimension (in respective directions facing toward each other) in this example, there may be other variations where vertical flow focusing feature (830) is fed by only one channel providing vertical flow focusingfluid. In such variations, such single channel may providevertical flowfocusing fluid to vertical flow focusing feature (830) along the x-dimension, along the z-dimension, or in any suitable direction. As yet another example, a fluid input port (310) and opening (410) may be positioned directly over flow focusing feature (830), or may collectively define flow focusing feature (830), such that there are no fluidic channels (732) feeding into flow focusing feature (830).

[0196] As shown in FIGS. 20-21, flow focusing feature (830) is positioned directly at the end of sample fluid receiving region (710), such that the arrangement of flow focusing feature (830), sample fluid receiving region (710), an intermediate fluidic channel (742) converge at a junction (746) that is different from junction (740) described above . Fluid containing sample cells flows through sample fluid receiving region (710) generally in the x- dimension, though the flow of the fluid may also have a component in the y -dimension as the fluid enters junction (746). Irrespective of the relationship between the component of the flow along the x-dimension and the component of the flow along the y-dimension as the fluid enters junction (746), the flow may provide a relatively even distribution of sample cells along the y- z plane as the flow enters junction (746), similar to the distribution shown in FIG. 15 A.

[0197] V ertical flow focusing fluid flows through flow f ocusing f eature (830) along the z-dimension, such that when the vertical flow focusing fluid enters junction (746) via flow focusing feature (830), the vertical flow focusing fluid bears downwardly along the flow of fluid containing sample cells. Thus, as the combined fluid exits junction (730) and continues along intermediate fluidic channel (742), the sample cells are substantially confined to the lower half of the z-y plane as described above with reference to FIG. 15B. This arrangement of sample cells may persist along the length of intermediate fluidic channel (742). The same horizontal flow focusing effects, and confinement of sample cells within the y-z plane as the sample cells pass through imaging region (900), described above in the context of fluid flow downstream of flow focusing feature (800) of FIGS. 13 -14 may also apply to the present context of flow focusing feature (830) of FIGS. 20-21.

[0198] As noted above, there maybe some variations where flow focusing along the z- dimension by flow focusing feature (830) occurs after flow focusing along the y-dimension. In other words, flow focusing feature (830) may be positioned downstream of second junction(750) in some variations. Moreover, some variations may omit a horizontal flow focusing (alongthe y-dimension) aspect, such that only vertical flow focusing (alongthe z-dimension) is provided.

[0199] E. Fifth Example of Vertical Flow Focusing Feature at JunctionBetween Channels

[0200] FIGS. 22-23 show a fifth example of a vertical flow focusing feature (840) that may be included in the fluid input region of FIG. 12, at junction (740). Flow focusing feature (840) of this example includes a circular recess (842) and a cylindrical passageway (844). Circular recess (842) is positioned along the same x-y plane as channels (712, 742), while cylindrical passageway (844) is positioned above circular recess (842) alongthe z-dimension. Circular recess (842) has a diameter (DI) along the x-y plane that is larger than the width (Wl) of channel (742) alongthe y-dimension. By way of example only, the diameter (DI) may range from approximately 50 pm to approximately 400 pm; or may be approximately 100 pm. In other examples, the diameter (DI) may have any other suitable value. Cylindrical passageway (844) has a diameter (D2) along the x-y plane that is larger than the diameter (DI) of circular recess (842). In some examples, circular recess (842) and cylindrical passageway (844) are each defined as a recess in the bottom surface (404) of layer (400).

[0201] While one fluidic channel (732a) of fluidic channels (732) is shown in FIG. 22, both fluidic channels (732) are intentionally omitted from FIG. 23 for clarity. While both fluidic channels (732) feed into flow focusing feature (840) along the y-dimension (in respective directions facing toward each other) in this example, there may be other variations where vertical flow focusing feature (840) is fed by only one channel providing vertical flow focusingfluid. In such variations, such single channel may providevertical flow focusing fluid to vertical flow focusing feature (840) along the x -dimension, alongthe z-dimension, or in any suitable direction. As yet another example, a fluid input port (310) and opening (410) may be positioned directly over flow focusing feature (840), or may collectively define flow focusing feature (840), such that there are no fluidic channels (732) feeding into flow focusing feature (840).

[0202] Fluid containing sample cells may enter junction (740) via fluidic channel (712) having with a relatively even distribution of sample cells alongthe y -z plane as described above with reference to FIG. 15 A. Vertical flow focusing fluid flows through flow focusing feature (840) along the z-dimension, such that when the vertical flow focusing fluid enters junction (740) via flow focusing feature (840), the vertical flow focusing fluid bears downwardly alongthe flow of fluid containing sample cells. Thus, as the combined fluid exits junction (740) and continues along intermediate fluidic channel (742), the sample cells are substantially confined to the lower half of the z-y plane as described above with reference to FIG. 15B. This arrangement of sample cells may persist along the length of intermediate fluidic channel (742). The same horizontal flow focusing effects, and confinement of sample cells within the y-z plane as the sample cells pass through imaging region (900), described above in the context of fluid flow downstream of flow focusing feature (800) of FIGS. 13 -14 may also apply to the present context of flow focusing feature (840) of FIGS. 22-23.

[0203] In some examples, the arrangement of flow focusing feature (840) may provide less risk of “dead volumes” or regions where vertical flow focusing does not sufficiently push cells to the lower region (along the z-dimension) of the outgoing fluid flow; as compared to the arrangement of flow focusing feature (820). In some examples, this dead volume reduction risk may be due, at least in part, to circular recess (842) having a diameter (DI) that is smaller than the diameter (D2) of cylindrical passageway (844) (as compared to circular recess (822) having a diameter (D2) that is larger than the diameter (DI) of cylindrical passageway (824) in flow focusing feature (820)). Flow focusing feature (840) may thus provide better flow focusing performance along the z-dimension than flow focusing feature (820) in some examples.

[0204] As noted above, there maybe some variations where flow focusing along the z- dimension by flow focusing feature (840) occurs after flow focusing along the y-dimension. In other words, flow focusing feature (840) may be positioned downstream of second junction (750) in some variations. Moreover, some variations may omit a horizontal flow focusing (along the y-dimension) aspect, such that only vertical flow focusing (along the z-dimension) is provided.

[0205] F. Sixth Example of Vertical Flow Focusing Feature at JunctionBetween Channels

[0206] FIGS. 24-25 show a sixth example of a vertical flow focusing feature (860) that may be included in the fluid input region of FIG. 12, at junction (740). Flow focusing feature (860) of this example is in the form of a cylindrical passageway, having a diameter (DI) along the x-y plane that is larger than the width (Wl) of channel (742) along the y-dimension. By way of example only, the diameter (DI) may range from approximately 50 pm to approximately 400 pm; or may be approximately 100 pm. In other examples, the diameter (D 1 ) may have any other suitable value. In some examples, the diameter (D 1 ) of flow f ocusingfeature (860) is at least approximately ten times the width (Wl) of channel (742).

[0207] The cylindrical passageway of flow focusing feature (860) extends along the z- dimension above the x-y plane of channels (712, 742). In some examples, the cylindrical passageway of flow focusing feature (860) is defined as a recess in the bottom surface (404) of layer (400). Unlike flow focusing feature (800) of FIGS. 13 -14, flow focusing feature (860) of FIGS. 24-25 is laterally offset from fluidic channels (712, 742). In particular, fluidic channels (712, 742) are aligned along a shared longitudinal axis (LA) extending along the x- dimension, while flow focusing feature (860) has a central axis (CAI) extending along the z- dimension, where the central axis (CAI) is offset from the longitudinal axis (LA) along the y- dimension by a distance (D3). By way of example only, the offset distance (D3) may range from approximately 25 pm to approximately 50 pm. In other examples, the offset distance (D3) may have any other suitable value.

[0208] While one fluidic channel (732a) of fluidic channels (732) is shown in FIG. 24, both fluidic channels (732) are intentionally omitted from FIG. 25 for clarity. While both fluidic channels (732) feed into flow focusing feature (860) along the y-dimension (in respective directions facing toward each other) in this example, there may be other variations where vertical flow focusing feature (860) is fed by only one channel providing vertical flow focusingfluid. In such variations, such single channel may providevertical flow focusing fluid to vertical flow focusing feature (860) alongthe x-dimension, along the z-dimension, or in any suitable direction. As yet another example, a fluid input port (310) and opening (410) may be positioned directly over flow focusing feature (860), or may collectively define flow focusing feature (860), such thatthere are no fluidic channels (732) feeding into flow focusing feature (860).

[0209] Fluid containing sample cells may enterjunction (740) via fluidic channel (712) having with a relatively even distribution of sample cells alongthe y -z plane as described above with reference to FIG. 15 A. Vertical flow focusing fluid flows through flow focusing feature (860) along the z-dimension, such that when the vertical flow focusing fluid enters junction (740) via flow focusing feature (860), the vertical flow focusing fluid bears downwardly along the flow of fluid containing sample cells. Thus, as the combined fluid exits junction (740) and continues along intermediate fluidic channel (742), the sample cells are substantially confined to the lower half of the z-y plane as described above with reference to FIG. 15B. This arrangement of sample cells may persist alongthe length of intermediate fluidic channel (742). The same horizontal flow focusing effects, and confinement of sample cells within the y-z plane as the sample cells pass through imaging region (900), described above in the context offluid flow downstream of flow focusing feature (800) of FIGS. 13 -14 may also apply to the present context of flow focusing feature (860) of FIGS. 24-25.

[0210] As noted above, there maybe some variations where flow focusing along the z- dimension by flow focusing feature (860) occurs after flow focusing along the y-dimension. In other words, flow focusing feature (860) may be positioned downstream of secondjunction (750) in some variations. Moreover, some variations may omit a horizontal flow focusing (along the y-dimension) aspect, such that only vertical flow focusing (along the z-dimension) is provided.

[0211] G. Seventh Example of Vertical Flow Focusing Feature at JunctionBetween Channels

[0212] FIGS. 26-27 show a seventh example of a vertical flow focusing feature (870) that may be included in the fluid input region of FIG. 12, at junction (740). Flow focusing feature (870) of this example includes a circular recess (872) and a cylindrical passageway (874). In some examples, circular recess (872) and cylindrical passageway (824) are each defined as a recess in the bottom surface (404) of layer (400). Circular recess (872) is positioned alongthe same x-y plane as channels (712, 742), while cylindrical passageway (874) is positioned above circular recess (872) alongthe z-dimension. Cylindrical passageway (874) has a diameter (DI) along the x-y plane that is larger than the width (Wl) of channel (742) along the y-dimension. By way of example only, the diameter (DI) may range from approximately 50 pm to approximately 400 pm; or may be approximately 100 pm. In other examples, the diameter (DI) may have any other suitable value. Circular recess (872) has a diameter (D2) along the x-y plane that is larger than the diameter (DI) of cylindrical passageway (824).

[0213] While circular recess (872) and cylindrical passageway (874) are both aligned with channels (712, 742) along the y-dimension, circular recess (872) and cylindrical passageway (874) are offset from each other along the x-dimension. In particular, fluidic channels (712, 742) are aligned along a shared longitudinal axis (LA) extending along the x- dimension, while cylindrical passageway (874) has a central axis (CA2) extending along the z- dimension and circular recess (872) has a central axis (CA3) extending alongthe z-dimension, where the central axes (CA2, CA3) are offset from each other along the x-dimension by a distance (D4). By way of example only, the offset distance (D4) may range from approximately 25 pm to approximately 200 pm; or may be approximately 100 pm. In other examples, the offset distance (D3) may have any other suitable value.

[0214] While one fluidic channel (732a) of fluidic channels (732) is shown in FIG. 26, both fluidic channels (732) are intentionally omitted from FIG. 27 for clarity. While both fluidic channels (732) feed into flow focusing feature (870) along the y-dimension (in respective directions facing toward each other) in this example, there may be other variations where vertical flow focusing feature (870) is fed by only one channel providing vertical flow focusingfluid. In such variations, such single channel may providevertical flow focusingfluid to vertical flow focusing feature (870) alongthe x-dimension, along the z-dimension, or in any suitable direction. As yet another example, a fluid input port (310) and opening (410) may be positioned directly over flow focusing feature (870), or may collectively define flow focusing feature (870), such thatthere are no fluidic channels (732) feeding into flow focusing feature (870).

[0215] Fluid containing sample cells may enterjunction (740) via fluidic channel (712) having with a relatively even distribution of sample cells alongthe y -z plane as described above with reference to FIG. 15 A. Vertical flow focusing fluid flows through flow focusing feature (870) along the z-dimension, such that when the vertical flow focusing fluid enters junction (740) via flow focusing feature (870), the vertical flow focusing fluid bears downwardly along the flow of fluid containing sample cells. Thus, as the combined fluid exits junction (740) and continues along intermediate fluidic channel (742), the sample cells are substantially confined to the lower half of the z-y plane as described above with reference to FIG. 15B. This arrangement of sample cells may persist alongthe length of intermediate fluidic channel (742). The same horizontal flow focusing effects, and confinement of sample cells within the y-z plane as the sample cells pass through imaging region (900), described above in the context of fluid flow downstream of flow focusing feature (800) of FIGS. 13-14 may also apply to the present context of flow focusing feature (870) of FIGS. 26-27.

[0216] As noted above, there maybe some variations where flow focusing alongthe z- dimension by flow focusing feature (870) occurs after flow focusing along the y-dimension. In other words, flow focusing feature (870) may be positioned downstream of secondjunction (750) in some variations. Moreover, some variations may omit a horizontal flow focusing (alongthe y-dimension) aspect, such that only vertical flow focusing (alongthe z-dimension) is provided.E. Example of Another Cartridge

[0217] FIG. 28 shows an example of another cartridge (1000) that may be used with system (100) in place of cartridge (200). Except as otherwise noted below, cartridge (1000) ofthis example may be structurally configured and operable like cartridge (200). Cartridge (1000) of this example includes a sample fluid receiving region (1002) and a flow control fluid receiving region (1004). A flow channel (1006) leads from sample fluid receiving region (1002) to a junction (1006). A pair of flow channels (1008) lead from flow control fluid receiving region (1004) to junction (1006). A sampling channel (1012) extends from junction (1006) to a bend (1014), which leads to a sample output region (1018) via an outlet channel (1016).

[0218] A cell containing fluid may be communicated through sample fluid receiving region (1002), and a flow control fluid may be communicated through flow control fluid receiving region (1004). These two fluids meet at junction (1010), which may provide a flow focusing feature like expanded recess (642), with the merged fluids being conveyed along sampling channel (1012). Light source (130) and optical assembly (132) illuminate imaging region (1020); while objective lens assembly (140) and camera (142) capture images of cells within imaging region (1020). The fluid continues around bend (1014), through outlet channel (1016), and exits cartridge (1000) at sample output region (1018). The fluid that exits cartridge (1000) at sample output region (1018) may be further conveyed to a reservoir that is either integrated into the instrument of system (100) or is external to the instrument.

[0219] Cartridge (1000) is thus similar to cartridge (200) exceptthat cartridge (1000) lacks the sorting capabilities of cartridge (200). Nevertheless, the other teachings provided above in the context of cartridge (200) may be readily applied to cartridge (1000).F. Examples of Combinations

[0220] The following examples relate to various non -exhaustive ways in which the teachings herein may be combined or applied. The following examples are not intended to restrict the coverage of any claims that may be presented at any time in this application or in sub sequent filings of this application. No disclaimer is intended. The following examples are being provided for nothing more than merely illustrative purposes. It is contemplated that the various teachings herein may be arranged and applied in numerous other ways. It is also contemplated that some variations may omit certain features referred to in the below examples. Therefore, none of the aspects or features referred to below should be deemed critical unless otherwise explicitly indicated as suchatalaterdateby the inventors orby a successor in interest to the inventors. If any claims are presentedin this application or in sub sequent filings related to this application that include additional features beyond those referred to below, those additional features shall not be presumed to have been added for any reason relating topatentability .

[0221] Example 1

[0222] An apparatus, comprising: a first fluidic channel to receive a fluid containing particles, the first fluidic channel having a first fluid flow resistance; a second fluidic channel to receive a horizontal flow control fluid, the second fluidic channel having a second fluid flow resistance; a third fluidic channel to receive the horizontal flow control fluid, the third fluidic channel having a third fluid flow resistance; a firstjunction, the first fluidic ch annel, the second fluidic channel, and the third fluidic channel joining together at the firstjunction; and a first outlet channel extending from the firstjunction to convey fluid from the firstjunction, the first outlet channel having a fourth fluid flow resistance; the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

[0223] Example 2

[0224] The apparatus of Example 1, the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other.

[0225] Example 3

[0226] The apparatus of any of Examples 1 through 2, the first fluid flow resistance ranging from approximately 1 / 5 of the second fluid flow resistance to approximately / i of the second fluid flow resistance.

[0227] Example 4

[0228] The apparatus of any of Examples 1 through 3, the first fluid flow resistance ranging from approximately 1 / 5 of the third fluid flow resistance to approximately / i of the third fluid flow resistance.

[0229] Example 5

[0230] The apparatus of any of Examples 1 through 4, the first fluid flow resistance ranging from approximately 1 / 5 of the fourth fluid flow resistance to approximately / i of the fourth fluid flow resistance.

[0231] Example 6

[0232] The apparatus of any of Examples 1 through 5, the first fluidic channel having a first length, the second fluidic channel having a second length, the third fluidic channel having a third length, the first outlet channel having a fourth length; and the first length being substantially shorter than each of the second length, the third length, and the fourth length.

[0233] Example 7

[0234] The apparatus of Example 6, the second length, the third length, and the fourthlength being approximately equal to each other.

[0235] Example 8

[0236] The apparatus of any of Examples 1 through 7, the first fluidic channel extending along a first horizontal dimension.

[0237] Example 9

[0238] The apparatus of Example 8, the first outlet channel extending along the first horizontal dimension.

[0239] Example 10

[0240] The apparatus of Example 9, the first fluidic channel and the first outlet channel being aligned with each other along the first horizontal dimension.

[0241] Example 11

[0242] The apparatus of any of Examples 8 through 10, the second fluidic channel extending along a second horizontal dimension.

[0243] Example 12

[0244] The apparatus of Example 11, the third fluidic channel extending along the second horizontal dimension.

[0245] Example 13

[0246] The apparatus of any of Examples 1 through 12, the first fluidic channel being substantially perpendicular to the second fluidic channel at the junction.

[0247] Example 14

[0248] The apparatus of any of Examples 1 through 13, the first fluidic channel being substantially perpendicular to the third fluidic channel at the junction.

[0249] Example 15

[0250] The apparatus of any of Examples 1 through 14, the first outlet channel being substantially perpendicular to the second fluidic channel at the junction.

[0251] Example 16

[0252] The apparatus of any of Examples 1 through 15, the first outlet channel being substantially perpendicular to the third fluidic channel at the junction.

[0253] Example 17

[0254] The apparatus of any of Examples 1 through 16, the horizontal flow control fluid from the second fluidic channel to focus the flow of the fluid containingparticles in a first direction in a first horizontal dimension as the fluid containing particles flows along a second horizontal dimension within the first outlet channel, the horizontal flow control fluid from the third fluidic channel to focus the flow of the fluid containing particles in a second direction inthe first horizontal dimension as the fluid containing particles flowsalongthe second horizontal dimension within the first outlet channel.

[0255] Example 18

[0256] The apparatus of any of Examples 1 through 17, the second fluidic channel including a mixing feature, the third fluidic channel including a mixing feature.

[0257] Example 19

[0258] The apparatus of Example 18, the mixing feature of the second fluidic channel including a set of recesses, the mixing feature of the third fluidic channel including a set of recesses.

[0259] Example 20

[0260] The apparatus of Example 19, the set of recesses of the second fluidic channel being in an upper surface of the second fluidic channel, the set of recesses of the third fluidic channel being in an upper surface of the third fluidic channel.

[0261] Example 21

[0262] The apparatus of any of Examples 19 through 20, the set of recesses of the second fluidic channel including chevron shapedrecesses, the set of recesses of the third fluidic channel including chevron shaped recesses.

[0263] Example 22

[0264] The apparatus of any of Examples 18 through 21, the mixing feature of the second fluidic channel to provide randomized arrangement of particles flowing through the second fluidic channel, the mixing feature of the third fluidic channel to provide randomized arrangement of particles flowing through the third fluidic channel.

[0265] Example 23

[0266] The apparatus of any of Examples 1 through 22, further comprising a vertical flow focusing feature, the vertical flow focusing feature to cause a vertical flow focusing fluid to focus the position of the particles along a vertical dimension within the first outlet channel as the particles flow along a horizontal dimension through the outlet channel.

[0267] Example 24

[0268] The apparatus of Example 23, further comprising a fourth fluidic channel to provide the vertical flow focusing fluid to the vertical flow focusing feature.

[0269] Example 25

[0270] The apparatus of Example 24, further comprising a fifth fluidic channel to provide the vertical flow focusing fluid to the vertical flow focusing feature.

[0271] Example 26

[0272] The apparatus of Example 25, further comprising a second junction, the fourth fluidic channel and the fifth fluidic channel joining together at the second junction.

[0273] Example 27

[0274] The apparatus of Example 26, the vertical flow focusing feature being positioned at the second junction.

[0275] Example 28

[0276] The apparatus of any of Examples 26 through 27, further comprising a sixth fluidic channel extending between the first junction and the second junction.

[0277] Example 29

[0278] The apparatus of Example 28, the second junction being positioned upstream of the first junction.

[0279] Example 30

[0280] The apparatus of any of Examples 23 through 29, the vertical flow focusing feature comprising a channel extending along a vertical dimension.

[0281] Example 31

[0282] The apparatus of Example 30, the channel comprising a recess in a bottom surface of a layer.

[0283] Example 32

[0284] The apparatus of any of Examples 30 through 31, the channel having a cylindrical shape.

[0285] Example 33

[0286] The apparatus of Example 32, the cylindrical shape having a diameter along a horizontal dimension, the first outlet channel having a width along the horizontal dimension, the diameter being greater than the width.

[0287] Example 34

[0288] The apparatus of any of Examples 23 through 33, further comprising a sample fluid receiving region, the sample fluid receiving region including a recess with a tapered region leading toward the first fluidic channel.

[0289] Example 35

[0290] The apparatus of Example 34, further comprising a fourth fluidic channel extendingfrom the tapered region, the vertical flow focusingfeature beingpositioned in a fluid path between the fourth fluidic channel and the first fluidic channel.

[0291] Example 36

[0292] The apparatus of Example 34, the vertical flow focusing feature beingpositioned in the tapered region of the sample fluid receiving region.

[0293] Example 37

[0294] The apparatus of any of Examples 23 through 36, the vertical flow focusing feature comprising: a recess extending along a horizontal dimension, and a channel extending along a vertical dimension over the recess.

[0295] Example 38

[0296] The apparatus of Example 37, the recess having a circular shape.

[0297] Example 39

[0298] The apparatus of any of Examples 37 through 38, the channel having a cylindrical shape.

[0299] Example 40

[0300] The apparatus of any of Examples 37 through 39, the recess having a first diameter, the channel having a second diameter, the second diameter being different from the first diameter.

[0301] Example 41

[0302] The apparatus of Example 40, the second diameter being smaller than the first diameter.

[0303] Example 42

[0304] The apparatus of Example 40, the second diameter being larger than the first diameter.

[0305] Example 43

[0306] The apparatus of any of Examples 37 through 42, the first fluidic channel, the second fluidic channel, the third fluidic channel, the first outlet channel, and the recess extending along a shared horizontal plane.

[0307] Example 44

[0308] The apparatus of any of Examples 37 through 43, the recess being centered along a first vertical axis, and the channel being centered along a second vertical axis.

[0309] Example 45

[0310] The apparatus of Example 44, the secondvertical axis being offsetfrom the first vertical axis along a horizontal dimension.

[0311] Example 46

[0312] The apparatus of Example 45, the first fluidic channel and the first outlet channel to convey fluids along the same horizontal dimension along which the secondvertical axis is offset from the first vertical axis.

[0313] Example 47

[0314] The apparatus of any of Examples 23, through 46, the vertical flow focusing feature being centered along a vertical axis, the first fluidic channel and the first outlet channel to convey fluids along a longitudinal axis extending along a first horizontal dimension, and the vertical axis being laterally offset from the longitudinal axis along a second horizontal dimension.

[0315] Example 48

[0316] The apparatus of any of Examples 1 through 47, further comprising a plurality of layers, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature extending through or along one or more of the layers of the plurality of layers.

[0317] Example 49

[0318] The apparatus of Example 48, at least one layer of the plurality of layers comprising poly dimethylsiloxane (PDMS).

[0319] Example 50

[0320] The apparatus of Example 49, a first layer of the plurality of layers comprising PDMS having a first thickness, and a second layer of the plurality of lay ers comprising PDMS having a second thickness.

[0321] Example 51

[0322] The apparatus of any of Examples 48 through 50, the plurality of layers comprising a layer of glass.

[0323] Example 52

[0324] The apparatus of any of Examples 48 through 51, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature comprising one or more respective recesses extending along one layer of the plurality of layers.

[0325] Example 53

[0326] The apparatus of any of Examples 1 through 52, further comprising an imaging region along the first outlet channel to image particles conveyed along the first outlet channel.

[0327] Example 54

[0328] The apparatus of any of Examples 1 through 53, further comprising: a second outlet channel; a third outlet channel; and a sortingjunction at an end of the first outlet channel, the sorting junction leading to the second outlet channel and the third outlet channel.

[0329] Example 55

[0330] The apparatus of Example 54, further comprising a first valve and a second valve, the first valve to selectively permit or prevent flow of fluid through the second outlet channel, the second valve to selectively permit or prevent flow of fluid through the third outlet channel.

[0331] Example 56

[0332] The apparatus of any of Examples 54 through 55, further comprising: a plurality of wells; and a plurality of additional fluidic channels, each additional fluidic channel of the plurality of additional fluidic channels leading to a respective well of the plurality of wells.

[0333] Example 57

[0334] The apparatus of Example 56, further comprising a plurality of valves, each valve of the plurality of valves to selectively permit or prevent flow of fluid through a respective additional fluidic channel of the plurality of additional fluidic channels.

[0335] Example 58

[0336] The apparatus of any of Examples 1 through 57, further comprising a sample fluid receiving region, the first fluidic channel to receive a fluid containing particles from an external source via the sample fluid receiving region.

[0337] Example 59

[0338] The apparatus of Example 58, the sample fluid receiving region including a recess having a teardrop shape.

[0339] Example 60

[0340] The apparatus of any of Examples 58 through 59, the sample fluid receiving region including a plurality of filtering elements.

[0341] Example 61

[0342] A method comprising: flowing a fluid containing particles along a first fluidic channel at a first fluid flow resistance; flowing a flow control fluid along a second fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel at a second fluid flow resistance; flowing the flow control fluid along a third fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel and while simultaneously flowing the flow control fluid along the second fluidic channel at a third fluid flow resistance; and allowing the flow of the fluid containing particles along the first fluidic channel to join the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel at a junction, thereby forming a joined fluid, the joined fluid exiting the junction along a first outlet channel and flowing at a fourth fluid flow resistance; the first fluid flow resistance being lower thaneach of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

[0343] Example 62

[0344] The method of Example 61, the second fluid flowresistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other.

[0345] Example 63

[0346] The method of any of Examples 61 through 62, the first fluid flow resistance ranging from approximately 1 / 5 of the second fluid flow resistance to approximately i of the second fluid flow resistance.

[0347] Example 64

[0348] The method of any of Examples 61 through 63 , the first fluid flow resistance ranging from approximately 1 / 5 of the third fluid flow resistance to approximately i of the third fluid flow resistance.

[0349] Example 65

[0350] The method of any of Examples 61 through 64, the first fluid flow resistance ranging from approximately 1 / 5 of the fourth fluid flow resistance to approximately i of the fourth fluid flow resistance.

[0351] Example 66

[0352] The method of any of Examples 61 through 65, the first fluidic channel having a first length, the second fluidic channel having a second length, the third fluidic channel having a third length, the first outlet channel having a fourth length; flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the first length; flowing the flow control fluid along the second fluidic channel including flowingthe flow control fluid alongthe second length; and flowingthe flow control fluid along the third fluidic channel including flowing the flow control fluid along the third length; the j oined fluid flowing alongthe f ourth length of the first outlet channel; and the first length b eing substantially shorter than each of the second length, the third length, and the fourth length.

[0353] Example 67

[0354] The method of Example 66, the second length, the third length, and the fourth length being approximately equal to each other.

[0355] Example 68

[0356] The method of any of Examples 61 through 67, the first fluidic channel extending along a first horizontal dimension; and flowingthe fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the firsthorizontal dimension.

[0357] Example 69

[0358] The method of Example 68, the first outlet channel extending along the first horizontal dimension; the joined fluid flowing along the first outlet channel along the first horizontal dimension.

[0359] Example 70

[0360] The method of Example 69, the first fluidic channel and the first outlet channel being aligned with each other along the first horizontal dimension.

[0361] Example 71

[0362] The method of any of Examples 68 through 70, the second fluidic channel extending along a second horizontal dimension; and flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along the second horizontal dimension.

[0363] Example 72

[0364] The method of Example 71 , the third fluidic channel extending alongthe second horizontal dimension; and flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid along the second horizontal dimension.

[0365] Example 73

[0366] The method of any of Examples 61 through 72, the first fluidic channel being substantially perpendicular to the second fluidic channel at the junction.

[0367] Example 74

[0368] The method of any of Examples 61 through 73, the first fluidic channel being substantially perpendicular to the third fluidic channel at the junction.

[0369] Example 75

[0370] The method of any of Examples 61 through 74, the first outlet channel being substantially perpendicular to the second fluidic channel at the junction.

[0371] Example 76

[0372] The method of any of Examples 61 through 75, the first outlet channel being substantially perpendicular to the third fluidic channel at the junction.

[0373] Example 77

[0374] The method of any of Examples 61 through 76, the flow control fluid from the second fluidic channel focusing the flow of the fluid containing particles in a first direction in a first horizontal dimension as the fluid containing particles flows along a second horizontal dimension within the first outlet channel, the flow control fluid from the third fluidic channelfocusingthe flow of the fluid containing particles in a second direction in the first horizontal dimension as the fluid containing particles flows along the second horizontal dimension within the first outlet channel.

[0375] Example 78

[0376] The method of any of Examples 61 through 77, flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along a first horizontal dimension.

[0377] Example 79

[0378] The method of Example 78, flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along a second horizontal dimension into the junction.

[0379] Example 80

[0380] The method of Example 79, flowing the flow control fluid along the second fluidic channel further including flowing the flow control fluid along a serpentine path before flowing the flow control fluid along the second horizontal dimension into the junction.

[0381] Example 81

[0382] The method of any of Examples 79 through 80, flowingthe flow control fluid along the third fluidic channel including flowing the flow control fluid along the second horizontal dimension into the junction.

[0383] Example 82

[0384] The method of Example 81 , flowingthe flow control fluid alongthe third fluidic channel further including flowing the flow control fluid along a serpentine path before flowing the flow control fluid along the second horizontal dimension into the junction.

[0385] Example 83

[0386] The method of any of Examples 61 through 82, the flow control fluid from the second fluidic channel focusing the position of the particles in a first direction along the a horizontal dimension within the outlet channel as the particles flow along a second horizontal dimension.

[0387] Example 84

[0388] The method of Example 83, the flow control fluid from the third fluidic channel focusing the position of the particles in a second direction alongthe first horizontal dimension within the outlet channel as the particles flow along the second horizontal dimension.

[0389] Example 85

[0390] The method of any of Examples 61 through 84, flowingthe flow control fluidalong the second fluidic channel including flowing the flow control fluid through a mixing feature of the second fluidic channel; and flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid through a mixing feature of the third fluidic channel.

[0391] Example 86

[0392] The method of Example 85, the mixing feature of the second fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the second fluidic channel including flowing the flow control fluid along the set of recesses of the mixing feature of the second fluidic channel; and the mixing feature of the third fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the third fluidic channel including flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel.

[0393] Example 87

[0394] The method of Example 86, the set of recesses of the second fluidic channel being in an upper surface of the second fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the second fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the second fluidic channel; and the set of recesses of the third fluidic channel being in an upper surface of the third fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the third fluidic channel.

[0395] Example 88

[0396] The method of any of Examples 85 through 87, the mixingfeature of the second fluidic channel providing randomized arrangement of particles flowing through the second fluidic channel, the mixing feature of the third fluidic channel providing randomized arrangement of particles flowing through the third fluidic channel.

[0397] Example 89

[0398] The method of any of Examples 61 through 88, further comprising flowing a vertical flow focusing fluid through a vertical flow focusing feature to focus the position of the particles along a vertical dimension within the first outlet channel as the particles flow along a horizontal dimension through the outlet channel.

[0399] Example 90

[0400] The method of Example 89, further comprising flowing the vertical flow focusing fluid through a fourth fluidic channel to thereby provide the vertical flow focusingfluid to the vertical flow focusing feature.

[0401] Example 91

[0402] The method of Example 90, further comprising flowing the vertical flow focusing fluid through a fifth fluidic channel to thereby provide the vertical flow focusing fluid to the vertical flow focusing feature.

[0403] Example 92

[0404] The method of Example 91, further comprising flowing the vertical flow focusingfluid through a second junction, the fourth fluidic channel and the fifth fluidic channel joining together at the second junction.

[0405] Example 93

[0406] The method of Example 92, the vertical flow focusing feature being positioned at the second junction.

[0407] Example 94

[0408] The method of any of Examples 89 through 93, the vertical flow focusing feature comprising a channel extending along a vertical dimension, flowing the vertical flow focusing fluid through the vertical flow focusing feature including flowing the vertical flow focusing fluid along the vertical dimension.

[0409] Example 95

[0410] The method of Example 94, the channel comprising a recess in a bottom surface of a layer, flowing the vertical flow focusing fluid through the vertical flow focusing feature including flowing the vertical flow focusing fluid into the recess.

[0411] Example 96

[0412] The method of any of Examples 94 through 95, the channel having a cylindrical shape.

[0413] Example 97

[0414] The method of Example 96, the cylindrical shape having a diameter along a horizontal dimension, the first outlet channel having a width along the horizontal dimension, the diameter being greater than the width.

[0415] Example 98

[0416] The method of any of Examples 89 through 97, the vertical flow focusing feature comprising: a recess extending along a horizontal dimension, and a channel extending along a vertical dimension over the recess; and flowingthe vertical flow focusingfluid through the vertical flow focusing feature including flowing the vertical flow focusing fluid into the channel and into the recess.

[0417] Example 99

[0418] The method of Example 98, the recess having a circular shape.

[0419] Example 100

[0420] The method of any of Examples 98 through 99, the channel having a cylindrical shape.

[0421] Example 101

[0422] The method of any of Examples 98 through 100, the recess having a first diameter, the channel having a second diameter, the second diameter being different from the first diameter.

[0423] Example 102

[0424] The method of Example 101, the second diameter being smaller than the first diameter.

[0425] Example 103

[0426] The method of Example 101, the second diameter being larger than the first diameter.

[0427] Example 104

[0428] The method of any of Examples 98 through 103, the first fluidic channel, the second fluidic channel, the third fluidic channel, the first outlet channel, and the recess extending along a shared horizontal plane; flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the shared horizontal plane; flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along the shared horizontal plane; flowing the flow control fluid along the third fluidic channel includingflowingthe flow control fluid alongthe shared horizontal plane; and the joined fluid flowing along the shared horizontal plane while flowing along the first outlet channel.

[0429] Example 105

[0430] Themethod of any of Examples98 through 104, the recess being centered along a first vertical axis, the channel being centered along a second vertical axis.

[0431] Example 106

[0432] The method of Example 105, the second vertical axis being offset from the first vertical axis along a horizontal dimension.

[0433] Example 107

[0434] The method of Example 106, flowing the fluid containing particles along the first fluidic channel includingflowingthe fluid containing particles alongthe same horizontaldimension along which the second vertical axis is offset from the first vertical axis; and the joined fluid flowing along the same horizontal dimension along which the second vertical axis is offset from the first vertical axis.

[0435] Example 108

[0436] The method of any of Examples 89, through 107, the vertical flow focusing feature being centered along a vertical axis; flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along a longitudinal axis extending along a first horizontal dimension, the vertical axis being laterally offset from the longitudinal axis along a second horizontal dimension; and the joined fluid flowing along the longitudinal axis.

[0437] Example 109

[0438] The method of any of Examples 61 through 108, further comprising capturing images of particles as the particles are conveyed along the first outlet channel.

[0439] Example 110

[0440] The method of Example 109, further comprising classifying or identifying the particles by analyzing the captured images.

[0441] Example 111

[0442] The method of Example 110, further comprising sorting particles from the outlet channel in response to classifying or identifyingthe particles b y analyzing the captured images.

[0443] Example 112

[0444] The method of Example 111, sorting particles including activating one or more valves to redirect fluid flow from the outlet channel to another outlet channel selected from a plurality of other outlet channels.

[0445] Example 113

[0446] The method of any of Examples 61 through 112, the particles including biological cells.

[0447] Example 1A

[0448] An apparatus, comprising: a first fluidic channel to receive a fluid containing particles; a second fluidic channel to receive a flow control fluid; a third fluidic channel to receive the flow control fluid; a junction, the first fluidic channel, the second fluidic channel, and the third fluidic channel joining together at the junction; a first outlet channel extending from the junction to convey fluid from the junction; and a flow focusing feature positioned at the junction, the flow focusing feature to cause the flow control fluid from the second fluidic channel and the third fluidic channel to focus the position of the particles along a verticaldimension and along a first horizontal dimension within the first outlet channel as the particles flow along a second horizontal dimension through the outlet channel.

[0449] Example 2A

[0450] The apparatus of Example 1 A, the second fluidic channel and the third fluidic channel having mirror symmetry with each other.

[0451] Example 3A

[0452] The apparatus of any of Examples 1 A through 2 A, the flow focusing feature comprising a recess positioned above the junction.

[0453] Example 4A

[0454] The apparatus of Example 3 A, the recess extending over a portion of the second fluidic channel.

[0455] Example 5A

[0456] The apparatus of any of Examples 3 A through 4 A, the recess extending over a portion of the third fluidic channel.

[0457] Example 6A

[0458] The apparatus of any of Examples 3 A through 5 A, the first fluidic channel having a width extending along the horizontal dimension, the recess having a length extending along the horizontal dimension, the length of the recess being greater than the width of the first fluidic channel.

[0459] Example 7A

[0460] The apparatus of any of Examples 3 A through 6 A, the recess having a rectangular shape.

[0461] Example 8A

[0462] The apparatus of any of Examples 1 A through 7A, the first fluidic channel extending along the second horizontal dimension.

[0463] Example 9A

[0464] The apparatus of any of Examples 1 A through 8 A, the first outlet channel extending along the second horizontal dimension.

[0465] Example 10A

[0466] The apparatus of any of Examples 1 A through 9 A, the first fluidic channel and the second fluidic channel being aligned with each other along the second horizontal dimension.

[0467] Example 11A

[0468] The apparatus of any of Examples 1 A through 10 A, the second fluidic channelextending along the first horizontal dimension.

[0469] Example 12 A

[0470] The apparatus of any of Examples 1 A through 11 A, the third fluidic channel extending along the first horizontal dimension.

[0471] Example 13A

[0472] The apparatus of any of Examples 1 A through 12 A, the second fluidic channel and the third fluidic channel being aligned with each other alongthe first horizontal dimension.

[0473] Example 14 A

[0474] The apparatus of any of Examples 1 A through 13 A, the first fluidic channel being perpendicular to the second fluidic channel at the junction.

[0475] Example 15 A

[0476] The apparatus of any of Examples 1 A through 14 A, the first fluidic channel being perpendicular to the third fluidic channel at the junction.

[0477] Example 16A

[0478] The apparatus of any of Examples 1 A through 15 A, the first outlet channel being perpendicular to the second fluidic channel at the junction.

[0479] Example 17A

[0480] The apparatus of any of Examples 1 A through 16 A, the first outlet channel being perpendicular to the third fluidic channel at the junction.

[0481] Example 18A

[0482] The apparatus of any of Examples 1 Athrough 17A, the flow focusing feature to cause the flow control fluid from the second fluidic channel and the third fluidic channel to flow in a first direction along the vertical dimension and then in a second direction alongthe vertical dimension to thereby focus the position of the particles in the second direction along the vertical dimension within the first outlet channel as the particles flow along a second horizontal dimension.

[0483] Example 19A

[0484] The apparatus of any of Examples 1 A through 18 A, the flow control fluid from the second fluidic channel to focus the position of the particles in a first direction alongthe first horizontal dimension within the first outlet channel as the particles flow along the second horizontal dimension.

[0485] Example 20A

[0486] The apparatus of any of Examples 1 A through 19 A, the flow control fluid from the third fluidic channel to focus the position of the particles in a second direction alongthefirst horizontal dimension within the first outlet channel as the particles flow along the second horizontal dimension.

[0487] Example 21 A

[0488] The apparatus of any of Examples 1 A through 20 A, the first fluidic channel having a first fluid flow resistance, the second fluidic channel having a second fluid flow resistance, the third fluidic channel having a third fluid flow resistance, the first outlet channel having a fourth fluid flow resistance; and the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

[0489] Example 22A

[0490] The apparatus of Example 21 A, the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flowresistancebeing approximately equal to each other.

[0491] Example 23A

[0492] The apparatus of any of Examples 1 A through 22 A, the second fluidic channel including a mixing feature, and the third fluidic channel including a mixing feature.

[0493] Example 24A

[0494] The apparatus of Example 23 A, the mixing feature of the second fluidic channel including a set of recesses, and the mixing feature of the third fluidic channel including a set of recesses.

[0495] Example 25A

[0496] The apparatus of Example 24 A, the set of recesses of the second fluidic channel being disposed over an upper surface of the second fluidic channel, and the set of recesses of the third fluidic channel being disposed over an upper surface of the third fluidic channel.

[0497] Example 26A

[0498] The apparatus of any of Examples 24 A through 25 A, the set of recesses of the second fluidic channel including chevron shaped recesses, and the set of recesses of the third fluidic channel including chevron shaped recesses.

[0499] Example 27A

[0500] The apparatus of any of Examples 23 A through 26 A, the mixing feature of the second fluidic channel to provide randomized arrangement of particles flowing through the second fluidic channel, and the mixing feature of the third fluidic channel to provide randomized arrangement of particles flowing through the third fluidic channel.

[0501] Example 28A

[0502] The apparatus of any of Examples 1 A through 27A, further comprising aplurality of layers, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature extending through or along one or more of the layers of the plurality of layers.

[0503] Example 29A

[0504] The apparatus of Example 28 A, at least one layer of the plurality of layers comprising poly dimethylsiloxane (PDMS).

[0505] Example 30 A

[0506] The apparatus of Example 29 A, a firstlayer of the plurality of layers comprisingPDMS having a first thickness, and a second layer of the plurality of lay ers comprising PDMS having a second thickness.

[0507] Example 31 A

[0508] The apparatus of any of Examples 28 A through 30A, the plurality of layers comprising a layer of glass.

[0509] Example 32A

[0510] The apparatus of any of Examples 28 A through 31 A, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature comprising one or more respective recesses extending along one layer of the plurality of layers.

[0511] Example 33A

[0512] The apparatus of any of Examples 1 A through 32 A, further comprising an imaging region along the first outlet channel to image particles conveyed along the first outlet channel.

[0513] Example 34A

[0514] The apparatus of any of Examples 1 A through 33 A, further comprising: a second outlet channel; a third outlet channel; and a sorting junction at an end of the first outlet channel, the sorting junction leading to the second outlet channel and the third outlet channel.

[0515] Example 35A

[0516] The apparatus of Example 34 A, further comprising a first valve and a second valve, the first valve to selectively permit or prevent flow of fluid through the second outlet channel, the second valve to selectively permit or prevent flow of fluid through the third outlet channel.

[0517] Example 36 A

[0518] The apparatus of any of Examples 34 A through 35 A, further comprising: a plurality of wells; and a plurality of additional fluidic channels, each additional fluidic channelof the plurality of additional fluidic channels leading to a respective well of the plurality of wells.

[0519] Example 37 A

[0520] The apparatus of Example 36 A, further comprising a plurality of valves, each valve of the plurality of valves to selectively permit or prevent flow of fluid through a respective additional fluidic channel of the plurality of additional fluidic channels.

[0521] Example 38 A

[0522] The apparatus of any ofExamples 1 Athrough 37 A, further comprising a sample fluid receiving region, the first fluidic channel to receive a fluid containing particles from an external source via the sample fluid receiving region.

[0523] Example 39 A

[0524] The apparatus of Example 38 A, the sample fluid receiving region including a recess having a teardrop shape.

[0525] Example 40A

[0526] The apparatus of any of Examples 38 A through 39A, the sample fluid receiving region including a plurality of filtering elements.

[0527] Example 41 A

[0528] A method comprising: flowing a fluid containing particles along a first fluidic channel; flowing a flow control fluid along a second fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel; flowing the flow control fluid along a third fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel and while simultaneously flowing the flow control fluid along the second fluidic channel; and allowing the flow of the fluid containing particles along the first fluidic channel to join the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel at a junction, thereby forming a joined fluid, the junction including an outlet channel and a flow focusing feature; the flow focusing feature causing the flow control fluid from the second fluidic channel and the third fluidic channel to focus the position of the particles along a vertical dimension and along a first horizontal dimension within the outlet channel as the particles flow in the joined fluid along a second horizontal dimension through the outlet channel.

[0529] Example 42A

[0530] The method of Example 41 A, the flow focusing feature comprising a recess positioned above the junction, allowing the flow of the fluid containing particles along the first fluidic channel to join the flow of the flow control fluid along the second fluidic channel andthe flow of the flow control fluid along the third fluidic channel at the junction comprising allowing the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel to enter the recess positioned above the junction.

[0531] Example 43A

[0532] The method of Example 42 A, the flow control fluid from the second fluidic channel and the flow control fluid from the third fluidic channel flowing upwardly into the recess then downwardly toward the outlet channel.

[0533] Example 44A

[0534] The method of any of Examples 41 A through 43 A, flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the second horizontal dimension.

[0535] Example 45A

[0536] The method of any of Examples 41 A through 44 A, flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along the first horizontal dimension into the junction.

[0537] Example 46A

[0538] The method of Example 45 A, flowing the flow control fluid along the second fluidic channel further including flowing the flow control fluid along a serpentine path before flowing the flow control fluid along the first horizontal dimension into the junction.

[0539] Example 47A

[0540] The method of any of Examples 41 A through 46 A, flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid along the first horizontal dimension into the junction.

[0541] Example 48A

[0542] The method of Example 47 A, flowing the flow control fluid along the third fluidic channel further including flowing the flow control fluid along a serpentine path before flowing the flow control fluid along the first horizontal dimension into the junction.

[0543] Example 49A

[0544] The method of any of Examples 41 A through 48 A, the flow control fluid from the second fluidic channel focusing the position of the particles in a first direction along the first horizontal dimension within the outlet channel as the particles flow along the second horizontal dimension.

[0545] Example 50A

[0546] The method of any of Examples 41 A through 49 A, the flow control fluid from the third fluidic channel focusing the position of the particles in a second direction alongthe first horizontal dimension within the outlet channel as the particles flow along the second horizontal dimension.

[0547] Example 51 A

[0548] The method of any of Examples 41 Athrough 50 A, the fluid containing particles flowing along the first fluidic channel at a first fluid flow resistance; the flow control fluid flowing along the second fluidic channel at a second fluid flow resistance; the flow control fluid flowing along the third fluidic channel at a third fluid flow resistance; the joined fluid flowing through the outlet channel at a fourth fluid flow resistance; and the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

[0549] Example 52A

[0550] The method of Example 51 A, the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other.

[0551] Example 53A

[0552] The method of any of Examples 41 A through 52 A, flowing the flow control fluid alongthe second fluidic channel includingflowingthe flow control fluid through a mixing feature of the second fluidic channel; and flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid through a mixing feature of the third fluidic channel.

[0553] Example 54A

[0554] The method of Example 53 A, the mixing feature of the second fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the second fluidic channel including flowing the flow control fluid alongthe set of recesses of the mixing feature of the second fluidic channel; and the mixing feature of the third fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the third fluidic channel including flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel.

[0555] Example 55A

[0556] The method of Example 54 A, the set of recesses of the second fluidic channel being disposed over an upper surface of the second fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the second fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of thesecond fluidic channel; and the set of recesses of the third fluidic channel being disposed over an upper surface of the third fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel including flowing th e flow control fluid upwardly into the set of recesses of the mixing feature of the third fluidic channel.

[0557] Example 56A

[0558] The method of any of Examples 53 A through 55 A, the mixing feature of the second fluidic channel providing randomized arrangement of particles flowing through the second fluidic channel, the mixing feature of the third fluidic channel providing randomized arrangement of particles flowing through the third fluidic channel.

[0559] Example 57A

[0560] The method of any of Examples 41 Athrough 56A, further comprising capturing images of particles as the particles are conveyed along the outlet channel.

[0561] Example 58A

[0562] The method of Example 57 A, further comprising classifying the particles by analyzing the captured images.

[0563] Example 59A

[0564] The method of Example 58A, further comprising sorting particles from the outlet channel in response to classifying or identifying the particles by analyzing the captured images.

[0565] Example 60A

[0566] The method of Example 59 A, sorting particles including activating one or more valves to redirect fluid flow from the outlet channel to another outlet channel selected from a plurality of other outlet channels.

[0567] Example 61 A

[0568] The method of any of Examples 41 A through 60 A, the particles including biological cells.

[0569] VII. Miscellaneous

[0570] While the examples provided above include cells or beads as particles, the teachings herein may be readily applied to other contexts where other kinds of particles are used in addition to or in lieu of cells or beads.

[0571] The foregoing description is provided to enable a person skilled in the art to practice the various configurations described herein. While the subject technology has been particularly described with reference to the various figures and configurations, it should beunderstood that these are for illustration purposes only and should not be taken as limiting the scope of the subject technology. The subject matter described herein is not limited in its application to the details of construction and the arrangement of components set forth in the description herein or illustrated in the drawings hereof. The subject matter described herein is capable of other implementations and of being practiced or ofbeing carried outin various ways.

[0572] It is to be understood that the above description is intended to be illustrative, and not restrictive. For example, the above -described examples (and / or aspects thereof) may be used in combination with each other. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the presently described subject matter without departing from its scope. While the dimensions, types of materials and coatings described herein are intended to define the parameters of the disclosed subject matter, they are by no means limiting and instead illustrations. Many further examples will be apparentto those of skill in the art upon reviewing the above description. The scope of the disclosed subject matter should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. Further, the limitations of the following claims are not written in means — plus-function format and are not intended to be interpreted based on 35 U.S.C. § 112(f), unless and until such claim limitations expressly use the phrase “means for” followed by a statement of function void of further structure.

[0573] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed in practicing the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0574] The following claims recite aspects of certain examples of the disclosed subject matter and are considered to be part of the above disclosure. These aspects may be combined with one another.

Claims

CLAIMSWhat is claimed is:

1. An apparatus, comprising: a first fluidic channel to receive a fluid containing particles, the first fluidic channel having a first fluid flow resistance; a second fluidic channel to receive a horizontal flow control fluid, the second fluidic channel having a second fluid flow resistance; a third fluidic channel to receive the horizontal flow control fluid, the third fluidic channel having a third fluid flow resistance; a first junction, the first fluidic channel, the second fluidic channel, and the third fluidic channel joining together at the first junction; and a first outlet channel extending from the first junction to convey fluid from the first junction, the first outlet channel having a fourth fluid flow resistance; the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

2. The apparatus of claim 1 , the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other.

3. The apparatus of any of claims 1 through 2, the first fluid flow resistance ranging from approximately 1 / 5 of the second fluid flow resistance to approximately / i of the second fluid flow resistance.

4. The apparatus of any of claims 1 through 3, the first fluid flow resistance ranging from approximately 1 / 5 of the third fluid flow resistance to approximately / i of the third fluid flow resistance.

5. The apparatus of any of claims 1 through 4, the first fluid flow resistance ranging from approximately 1 / 5 of the fourth fluid flow resistance to approximately / i of the fourth fluid flow resistance.

6. The apparatus of any of claims 1 through 5, the first fluidic channel having a first length, the second fluidic channel having a second length, the third fluidic channel having a third length, the first outlet channel having a fourth length; and the first length being substantially shorter than each of the second length, the third length, and the fourth length.

7. The apparatus of claim 6, the second length, the third length, and the fourth length being approximately equal to each other.

8. The apparatus of any of claims 1 through 7, the first fluidic channel extending along a first horizontal dimension.

9. The apparatus of claim 8, the first outlet channel extending along the first horizontal dimension.

10. The apparatus of claim 9, the first fluidic channel and the first outlet channel being aligned with each other along the first horizontal dimension.

11. The apparatus of any of claims 8 through 10, the second fluidic channel extending along a second horizontal dimension.

12. The apparatus of claim 11, the third fluidic channel extending along the second horizontal dimension.

13. The apparatus of any of claims 1 through 12, the first fluidic channel being substantially perpendicular to the second fluidic channel at the junction.

14. The apparatus of any of claims 1 through 13, the first fluidic channel being substantially perpendicular to the third fluidic channel at the junction.

15. The apparatus of any of claims 1 through 14, the first outlet channel being substantially perpendicular to the second fluidic channel at the junction.

16. The apparatus of any of claims 1 through 15, the first outlet channel being substantially perpendicular to the third fluidic channel at the junction.

17. The apparatus of any of claims 1 through 16, the horizontal flow control fluid from the second fluidic channel to focus the flow of the fluid containing particles in a first direction in a first horizontal dimension as the fluid containing particles flows along a second horizontal dimension within the first outlet channel, the horizontal flow control fluid from the third fluidic channel to focus the flow of the fluid containing particles in a second direction in the first horizontal dimension as the fluid containing particles flows along the second horizontal dimension within the first outlet channel.

18. The apparatus of any of claims 1 through 17, the second fluidic channel including a mixing feature, the third fluidic channel including a mixing feature.

19. The apparatus of claim 18, the mixing feature of the second fluidic channel including a set of recesses, the mixing feature of the third fluidic channel including a set of recesses.

20. The apparatus of claim 19, the set of recesses of the second fluidic channel being in an upper surface of the second fluidic channel, the set of recesses of the third fluidic channel being in an upper surface of the third fluidic channel.

21. The apparatus of any of claims 19 through 20, the set of recesses of the second fluidic channel including chevron shaped recesses, the set of recesses of the third fluidic channel including chevron shaped recesses.

22. The apparatus of any of claims 18 through 21, the mixing feature of the second fluidic channel to provide randomized arrangement of particles flowing through the second fluidic channel, the mixing feature of the third fluidic channel to provide randomized arrangement of particles flowing through the third fluidic channel.

23. The apparatus of any of claims 1 through 22, further comprising a vertical flow focusing feature, the vertical flow focusing feature to cause a vertical flow focusingfluid to focus the position of the particles along a vertical dimension within the first outlet channel as the particles flow along a horizontal dimension through the outlet channel.

24. The apparatus of claim 23, further comprising a fourth fluidic channel to provide the vertical flow focusing fluid to the vertical flow focusing feature.

25. The apparatus of claim 24, further comprising a fifth fluidic channel to provide the vertical flow focusing fluid to the vertical flow focusing feature.

26. The apparatus of claim 25, further comprising a second junction, the fourth fluidic channel and the fifth fluidic channel joining together at the second junction.

27. The apparatus of claim 26, the vertical flow focusing feature being positioned at the second junction.

28. The apparatus of any of claims 26 through 27, further comprising a sixth fluidic channel extending between the first junction and the second junction.

29. The apparatus of claim 28, the second junction being positioned upstream of the first junction.

30. The apparatus of any of claims 23 through 29, the vertical flow focusing feature comprising a channel extending along a vertical dimension.

31. The apparatus of claim 30, the channel comprising a recess in a bottom surface of a layer.

32. The apparatus of any of claims 30 through 31, the channel having a cylindrical shape.

33. The apparatus of claim 32, the cylindrical shape having a diameter along a horizontal dimension, the first outlet channel having a width along the horizontal dimension, the diameter being greater than the width.

34. The apparatus of any of claims 23 through 33, further comprising a sample fluid receiving region, the sample fluid receiving region including a recess with a tapered region leading toward the first fluidic channel.

35. The apparatus of claim 34, further comprising a fourth fluidic channel extending from the tapered region, the vertical flow focusing feature being positioned in a fluid path between the fourth fluidic channel and the first fluidic channel.

36. The apparatus of claim 34, the vertical flow focusing feature being positioned in the tapered region of the sample fluid receiving region.

37. The apparatus of any of claims 23 through 36, the vertical flow focusing feature comprising: a recess extending along a horizontal dimension, and a channel extending along a vertical dimension over the recess.

38. The apparatus of claim 37, the recess having a circular shape.

39. The apparatus of any of claims 37 through 38, the channel having a cylindrical shape.

40. The apparatus of any of claims 37 through 39, the recess having a first diameter, the channel having a second diameter, the second diameter being different from the first diameter.41 . The apparatus of claim 40, the second diameter being smaller than the first diameter.

42. The apparatus of claim 40, the second diameter being larger than the first diameter.

43. The apparatus of any of claims 37 through 42, the first fluidic channel, the second fluidic channel, the third fluidic channel, the first outlet channel, and the recess extending along a shared horizontal plane.

44. The apparatus of any of claims 37 through 43, the recessbeing centered along a first vertical axis, and the channel being centered along a second vertical axis.

45. The apparatus of claim 44, the second vertical axis being offset f rom the first vertical axis along a horizontal dimension.

46. The apparatus of claim 45, the first fluidic channel and the first outlet channel to convey fluids along the same horizontal dimension along which the second vertical axis is offset from the first vertical axis.

47. The apparatus of any of claims 23, through 46, the vertical flow focusing feature being centered along a vertical axis, the first fluidic channel and the first outlet channel to convey fluids along a longitudinal axis extending along a first horizontal dimension, and the vertical axis being laterally offset from the longitudinal axis along a second horizontal dimension.

48. The apparatus of any of claims 1 through 47, further comprising a plurality of layers, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature extending through or along one or more of the layers of the plurality of layers.

49. The apparatus of claim 48, at least one layer of the plurality of layers comprising polydimethylsiloxane (PDMS).

50. The apparatus of claim 49, a first layer of the plurality of layers comprising PDMS having a first thickness, and a second layer of the plurality of layers comprising PDMS having a second thickness.

51. The apparatus of any of claims 48 through 50, the plurality of layers comprising a layer of glass.

52. The apparatus of any of claims 48 through 51, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, andthe flow focusing feature comprising one or more respective recesses extending along one layer of the plurality of layers.

53. The apparatus of any of claims 1 through 52, further comprising an imaging region along the first outlet channel to image particles conveyed along the first outlet channel.

54. The apparatus of any of claims 1 through 53, further comprising: a second outlet channel; a third outlet channel; and a sorting junction at an end of the first outlet channel, the sorting junction leading to the second outlet channel and the third outlet channel.

55. The apparatus of claim 54, further comprising a first valve and a second valve, the first valve to selectively permit or prevent flow of fluid through the second outlet channel, the second valve to selectively permit or prevent flow of fluid through the third outlet channel.

56. The apparatus of any of claims 54 through 55, further comprising: a plurality of wells; and a plurality of additional fluidic channels, each additional fluidic channel of the plurality of additional fluidic channels leading to a respective well of the plurality of wells.

57. The apparatus of claim 56, further comprising a plurality of valves, each valve of the plurality of valves to selectively permit or prevent flow of fluid through a respective additional fluidic channel of the plurality of additional fluidic channels.

58. The apparatus of any of claims 1 through 57, further comprising a sample fluid receiving region, the first fluidic channel to receive a fluid containing particles from an external source via the sample fluid receiving region.

59. The apparatus of claim 58, the sample fluid receiving region including a recess having a teardrop shape.

60. The apparatus of any of claims 58 through 59, the sample fluid receiving region including a plurality of filtering elements.

61. A method comprising: flowing a fluid containing particles along a first fluidic channel at a first fluid flow resistance; flowing a flow control fluid along a second fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel at a second fluid flow resistance; flowing the flow control fluid along a third fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel and while simultaneously flowing the flow control fluid along the second fluidic channel at a third fluid flow resistance; and allowing the flow of the fluid containing particles along the first fluidic channel to join the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel at a junction, thereby forming a joined fluid, the joined fluid exiting the junction along a first outlet channel and flowing at a fourth fluid flow resistance; the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

62. The method of claim 61 , the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other.

63. The method of any of claims 61 through 62, the first fluid flow resistance ranging from approximately 1 / 5 of the second fluid flow resistance to approximately / i of the second fluid flow resistance.

64. The method of any of claims 61 through 63, the first fluid flow resistance ranging from approximately 1 / 5 of the third fluid flow resistance to approximately / i of the third fluid flow resistance.

65. The method of any of claims 61 through 64, the first fluid flow resistance ranging from approximately 1 / 5 of the fourth fluid flow resistance to approximately Yi of the fourth fluid flow resistance.

66. The method of any of claims 61 through 65, the first fluidic channel having a first length, the second fluidic channel having a second length, the third fluidic channel having a third length, the first outlet channel having a fourth length; flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the first length; flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along the second length; and flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid along the third length; the joined fluid flowing along the fourth length of the first outlet channel; and the first length being substantially shorter than each of the second length, the third length, and the fourth length.

67. The method of claim 66, the second length, the third length, and the fourth length being approximately equal to each other.

68. The method of any of claims 61 through 67, the first fluidic channel extending along a first horizontal dimension; and flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the first horizontal dimension.

69. The method of claim 68, the first outlet channel extending along the first horizontal dimension; the joined fluid flowing along the first outlet channel along the first horizontal dimension.

70. The method of claim 69, the first fluidic channel and the first outlet channel being aligned with each other along the first horizontal dimension.

71. The method of any of claims 68 through 70, the second fluidic channel extending along a second horizontal dimension; and flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along the second horizontal dimension.

72. The method of claim 71, the third fluidic channel extending along the second horizontal dimension; and flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid along the second horizontal dimension.

73. The method of any of claims 61 through 72, the first fluidic channel being substantially perpendicular to the second fluidic channel at the junction.

74. The method of any of claims 61 through 73, the first fluidic channel being substantially perpendicular to the third fluidic channel at the junction.

75. The method of any of claims 61 through 74, the first outlet channel being substantially perpendicular to the second fluidic channel at the junction.

76. The method of any of claims 61 through 75, the first outlet channel being substantially perpendicular to the third fluidic channel at the junction.

77. The method of any of claims 61 through 76, the flow control fluid from the second fluidic channel focusing the flow of the fluid containing particles in a first direction in a first horizontal dimension as the fluid containing particles flows along a second horizontal dimension within the first outlet channel, the flow control fluid from the third fluidic channel focusing the flow of the fluid containing particles in a second direction in the first horizontal dimension as the fluid containing particles flows along the second horizontal dimension within the first outlet channel.

78. The method of any of claims 61 through 77, flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along a first horizontal dimension.

79. The method of claim 78, flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along a second horizontal dimension into the junction.

80. The method of claim 79, flowing the flow control fluid along the second fluidic channel further including flowing the flow control fluid along a serpentine path before flowing the flow control fluid along the second horizontal dimension into the junction.

81. The method of any of claims 79 through 80, flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid along the second horizontal dimension into the junction.

82. The method of claim 81, flowing the flow control fluid along the third fluidic channel further including flowing the flow control fluid along a serpentine path before flowing the flow control fluid along the second horizontal dimension into the junction.

83. The method of any of claims 61 through 82, the flow control fluid from the second fluidic channel focusing the position of the particles in a first direction along the a horizontal dimension within the outlet channel as the particles flow along a second horizontal dimension.

84. The method of claim 83, the flow control fluid from the third fluidic channel focusing the position of the particles in a second direction along the first horizontal dimension within the outlet channel as the particles flow along the second horizontal dimension.

85. The method of any of claims 61 through 84, flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid through a mixing feature of the second fluidic channel; and flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid through a mixing feature of the third fluidic channel.

86. The method of claim 85, the mixing feature of the second fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of thesecond fluidic channel including flowing the flow control fluid along the set of recesses of the mixing feature of the second fluidic channel; and the mixing feature of the third fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the third fluidic channel including flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel.

87. The method of claim 86, the set of recesses of the second fluidic channel being in an upper surface of the second fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the second fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the second fluidic channel; and the set of recesses of the third fluidic channel being in an upper surface of the third fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the third fluidic channel.

88. The method of any of claims 85 through 87, the mixing feature of the second fluidic channel providing randomized arrangement of particles flowing through the second fluidic channel, the mixing feature of the third fluidic channel providing randomized arrangement of particles flowing through the third fluidic channel.

89. The method of any of claims 61 through 88, further comprising flowing a vertical flow focusing fluid through a vertical flow focusing feature to focus the position of the particles along a vertical dimension within the first outlet channel as the particles flow along a horizontal dimension through the outlet channel.

90. The method of claim 89, further comprising flowing the vertical flow focusing fluid through a fourth fluidic channel to thereby provide the vertical flow focusing fluid to the vertical flow focusing feature.

91. The method of claim 90, further comprising flowing the vertical flow focusing fluid through a fifth fluidic channel to thereby provide the vertical flow focusing fluid to the vertical flow focusing feature.

92. The method of claim 91, further comprising flowing the vertical flow focusing fluid through a second junction, the fourth fluidic channel and the fifth fluidic channel joining together at the second junction.

93. The method of claim 92, the vertical flow focusing feature being positioned at the second junction.

94. The method of any of claims 89 through 93, the vertical flow focusing feature comprising a channel extending along a vertical dimension, flowing the vertical flow focusing fluid through the vertical flow focusing feature including flowing the vertical flow focusing fluid along the vertical dimension.

95. The method of claim 94, the channel comprising a recess in a bottom surface of a layer, flowing the vertical flow focusing fluid through the vertical flow f ocusing feature including flowing the vertical flow focusing fluid into the recess.

96. The method of any of claims 94 through 95, the channel having a cylindrical shape.

97. The method of claim 96, the cylindrical shape having a diameter along a horizontal dimension, the first outlet channel having a width along the horizontal dimension, the diameter being greater than the width.

98. The method of any of claims 89 through 97, the vertical flow focusing feature comprising: a recess extending along a horizontal dimension, and a channel extending along a vertical dimension over the recess; and flowing the vertical flow focusing fluid through the vertical flow focusing feature including flowing the vertical flow focusing fluid into the channel and into the recess.

99. The method of claim 98, the recess having a circular shape.

100. The method of any of claims 98 through 99, the channel having a cylindrical shape.

101. The method of any of claims 98 through 100, the recess having a first diameter, the channel having a second diameter, the second diameter being different from the first diameter.

102. The method of claim 101, the second diameter being smaller than the first diameter.

103. The method of claim 101, the second diameter being larger than the first diameter.

104. The method of any of claims 98 through 103, the first fluidic channel, the second fluidic channel, the third fluidic channel, the first outlet channel, and the recess extending along a shared horizontal plane; flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the shared horizontal plane; flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along the shared horizontal plane; flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid along the shared horizontal plane; and the joined fluid flowing along the shared horizontal plane while flowing along the first outlet channel.

105. The method of any of claims 98 through 104, the recess being centered along a first vertical axis, the channel being centered along a second vertical axis.

106. The method of claim 105, the second vertical axis being offset from the first vertical axis along a horizontal dimension.

107. The method of claim 106, flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the same horizontal dimension along which the second vertical axis is offset from the first vertical axis; and the joined fluid flowing along the same horizontal dimension along which the second vertical axis is offset from the first vertical axis.

108. The method of any of claims 89, through 107, the vertical flow focusing feature being centered along a vertical axis; flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along a longitudinal axis extending along a first horizontal dimension, the vertical axis being laterally offset from the longitudinal axis along a second horizontal dimension; and the joined fluid flowing along the longitudinal axis.

109. The method of any of claims 61 through 108, further comprising capturing images of particles as the particles are conveyed along the first outlet channel.

110. The method of claim 109, further comprising classifying or identifying the particles by analyzing the captured images.

111. The method of claim 110, further comprising sorting particles from the outlet channel in response to classifying or identifying the particles by analyzing the captured images.

112. The method of claim 111, sorting particles including activating one or more valves to redirect fluid flow from the outlet channel to another outlet channel selected from a plurality of other outlet channels.

113. The method of any of claims 61 through 112, the particles including biological cells.

114. An apparatus, comprising: a first fluidic channel to receive a fluid containing particles; a second fluidic channel to receive a flow control fluid; a third fluidic channel to receive the flow control fluid; a junction, the first fluidic channel, the second fluidic channel, and the third fluidic channel joining together at the junction; a first outlet channel extending from the junction to convey fluid from the junction; and a flow focusing feature positioned at the junction, the flow focusing feature to cause the flow control fluid from the second fluidic channel and thethird fluidic channel to focus the position of the particles along a vertical dimension and along a first horizontal dimension within the first outlet channel as the particles flow along a second horizontal dimension through the outlet channel.

115. The apparatus of claim 114, the second fluidic channel and the third fluidic channel having mirror symmetry with each other.

116. The apparatus of any of claims 114 through 115, the flow focusing feature comprising a recess positioned above the junction.

117. The apparatus of claim 116, the recess extending over a portion of the second fluidic channel.

118. The apparatus of any of claims 116 through 117, the recess extending over a portion of the third fluidic channel.

119. The apparatus of any of claims 116 through 118, the first fluidic channel having a width extending along the horizontal dimension, the recess having a length extending along the horizontal dimension, the length of the recess being greater than the width of the first fluidic channel.

120. The apparatus of any of claims 116 through 119, the recess having a rectangular shape.

121. The apparatus of any of claims 114 through 120, the first fluidic channel extending along the second horizontal dimension.

122. The apparatus of any of claims 114 through 121, the first outlet channel extending along the second horizontal dimension.

123. The apparatus of any of claims 114 through 122, the first fluidic channel and the second fluidic channel being aligned with each other along the second horizontal dimension.

124. The apparatus of any of claims 114 through 123, the second fluidic channel extending along the first horizontal dimension.

125. The apparatus of any of claims 114 through 124, the third fluidic channel extending along the first horizontal dimension.

126. The apparatus of any of claims 114 through 125, the second fluidic channel and the third fluidic channel being aligned with each other along the first horizontal dimension.

127. The apparatus of any of claims 114 through 126, the first fluidic channel being perpendicular to the second fluidic channel at the junction.

128. The apparatus of any of claims 114 through 127, the first fluidic channel being perpendicular to the third fluidic channel at the junction.

129. The apparatus of any of claims 114 through 128, the first outlet channel being perpendicular to the second fluidic channel at the junction.

130. The apparatus of any of claims 114 through 129, the first outlet channel being perpendicular to the third fluidic channel at the junction.

131. The apparatus of any of claims 114 through 130, the flow focusing feature to cause the flow control fluid from the second fluidic channel and the third fluidic channel to flow in a first direction along the vertical dimension and then in a second direction along the vertical dimension to thereby focus the position of the particles in the second direction along the vertical dimension within the first outlet channel as the particles flow along a second horizontal dimension.

132. The apparatus of any of claims 114 through 131, the flow control fluid from the second fluidic channel to focus the position of the particles in a first direction along the first horizontal dimension within the first outlet channel as the particles flow along the second horizontal dimension.

133. The apparatus of any of claims 114 through 132, the flow control fluid from the third fluidic channel to focus the position of the particles in a second direction along the first horizontal dimension within the first outlet channel as the particles flow along the second horizontal dimension.

134. The apparatus of any of claims 114 through 133, the first fluidic channel having a first fluid flow resistance, the second fluidic channel having a second fluid flow resistance, the third fluidic channel having a third fluid flow resistance, the first outlet channel having a fourth fluid flow resistance; and the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

135. The apparatus of claim 134, the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other.

136. The apparatus of any of claims 114 through 135, the second fluidic channel including a mixing feature, and the third fluidic channel including a mixing feature.

137. The apparatus of claim 136, the mixing feature of the second fluidic channel including a set of recesses, and the mixing feature of the third fluidic channel including a set of recesses.

138. The apparatus of claim 137, the set of recesses of the second fluidic channel being disposed over an upper surface of the second fluidic channel, and the set of recesses of the third fluidic channel being disposed over an upper surface of the third fluidic channel.

139. The apparatus of any of claims 137 through 138, the set of recesses of the second fluidic channel including chevron shaped recesses, and the set of recesses of the third fluidic channel including chevron shaped recesses.

140. The apparatus of any of claims 136 through 139, the mixing feature of the second fluidic channel to provide randomized arrangement of particles flowing through the second fluidic channel, and the mixing feature of the third fluidic channel to provide randomized arrangement of particles flowing through the third fluidic channel.

141. The apparatus of any of claims 114 through 140, further comprising a plurality of layers, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature extending through or along one or more of the layers of the plurality of layers.

142. The apparatus of claim 141, at least one layer of the plurality of layers comprising polydimethylsiloxane (PDMS).

143. The apparatus of claim 142, a first layer of the plurality of layers comprising PDMS having a first thickness, and a second layer of the plurality of layers comprising PDMS having a second thickness.

144. The apparatus of any of claims 141 through 143, the plurality of layers comprising a layer of glass.

145. The apparatus of any of claims 141 through 144, each of the first fluidic channel, the second fluidic channel, the third fluidic channel, the junction, the first outlet channel, and the flow focusing feature comprising one or more respective recesses extending along one layer of the plurality of layers.

146. The apparatus of any of claims 114 through 145, further comprising an imaging region along the first outlet channel to image particles conveyed along the first outlet channel.

147. The apparatus of any of claims 114 through 146, further comprising: a second outlet channel; a third outlet channel; and a sorting junction at an end of the first outlet channel, the sorting junction leading to the second outlet channel and the third outlet channel.

148. The apparatus of claim 147, further comprising a first valve and a second valve, the first valve to selectively permit or prevent flow of fluid through the second outlet channel, the second valve to selectively permit or prevent flow of fluid through the third outlet channel.

149. The apparatus of any of claims 147 through 148, further comprising: a plurality of wells; and a plurality of additional fluidic channels, each additional fluidic channel of the plurality of additional fluidic channels leading to a respective well of the plurality of wells.

150. The apparatus of claim 149, further comprising a plurality of valves, each valve of the plurality of valves to selectively permit or prevent flow of fluid through a respective additional fluidic channel of the plurality of additional fluidic channels.

151. The apparatus of any of claims 114 through 150, further comprising a sample fluid receiving region, the first fluidic channel to receive a fluid containing particles from an external source via the sample fluid receiving region.

152. The apparatus of claim 151, the sample fluid receiving region including a recess having a teardrop shape.

153. The apparatus of any of claims 151 through 152, the sample fluid receiving region including a plurality of filtering elements.

154. A method comprising: flowing a fluid containing particles along a first fluidic channel; flowing a flow control fluid along a second fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel; flowing the flow control fluid along a third fluidic channel while simultaneously flowing the fluid containing particles along the first fluidic channel and while simultaneously flowing the flow control fluid along the second fluidic channel; and allowing the flow of the fluid containing particles along the first fluidic channel to join the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel at a junction, thereby forming a joined fluid, the junction including an outlet channel and a flow focusing feature;the flow focusing feature causing the flow control fluid from the second fluidic channel and the third fluidic channel to focus the position of the particles along a vertical dimension and along a first horizontal dimension within the outlet channel as the particles flow in the joined fluid along a second horizontal dimension through the outlet channel.

155. The method of claim 154, the flow focusing feature comprising a recess positioned above the junction, allowing the flow of the fluid containing particles along the first fluidic channel to join the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel at the junction comprising allowing the flow of the flow control fluid along the second fluidic channel and the flow of the flow control fluid along the third fluidic channel to enter the recess positioned above the junction.

156. The method of claim 155, the flow control fluid from the second fluidic channel and the flow control fluid from the third fluidic channel flowing upwardly into the recess then downwardly toward the outlet channel.

157. The method of any of claims 154 through 156, flowing the fluid containing particles along the first fluidic channel including flowing the fluid containing particles along the second horizontal dimension.

158. The method of any of claims 154through 157, flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid along the first horizontal dimension into the junction.

159. The method of claim 158, flowing the flow control fluid along the second fluidic channel further including flowing the flow control fluid along a serpentine path before flowing the flow control fluid along the first horizontal dimension into the junction.

160. The method of any of claims 154through 159, flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid along the first horizontal dimension into the junction.

161. The method of claim 160, flowing the flow control fluid along the third fluidic channel further including flowing the flow control fluid along a serpentine path before flowing the flow control fluid along the first horizontal dimension into the junction.

162. The method of any of claims 154through 161, the flow control fluid from the second fluidic channel focusing the position of the particles in a first direction along the first horizontal dimension within the outlet channel as the particles flow along the second horizontal dimension.

163. The method of any of claims 154 through 162, the flow control fluid from the third fluidic channel focusing the position of the particles in a second direction along the first horizontal dimension within the outlet channel as the particles flow along the second horizontal dimension.

164. The method of any of claims 154 through 163, the fluid containing particles flowing along the first fluidic channel at a first fluid flow resistance; the flow control fluid flowing along the second fluidic channel at a second fluid flow resistance; the flow control fluid flowing along the third fluidic channel at a third fluid flow resistance; the joined fluid flowing through the outlet channel at a fourth fluid flow resistance; and the first fluid flow resistance being lower than each of the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance.

165. The method of claim 164, the second fluid flow resistance, the third fluid flow resistance, and the fourth fluid flow resistance being approximately equal to each other.

166. The method of any of claims 154through 165, flowing the flow control fluid along the second fluidic channel including flowing the flow control fluid through a mixing feature of the second fluidic channel; and flowing the flow control fluid along the third fluidic channel including flowing the flow control fluid through a mixing feature of the third fluidic channel.

167. The method of claim 166, the mixing feature of the second fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the second fluidic channel including flowing the flow control fluid along the set of recesses of the mixing feature of the second fluidic channel; and the mixing feature of the third fluidic channel including a set of recesses, flowing the flow control fluid through the mixing feature of the third fluidic channel including flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel.

168. The method of claim 167, the set of recesses of the second fluidic channel being disposed over an upper surface of the second fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the second fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the second fluidic channel; and the set of recesses of the third fluidic channel being disposed over an upper surface of the third fluidic channel, flowing the flow control fluid along the set of recesses of the mixing feature of the third fluidic channel including flowing the flow control fluid upwardly into the set of recesses of the mixing feature of the third fluidic channel.

169. The method of any of claims 166 through 168, the mixing feature of the second fluidic channel providing randomized arrangement of particles flowing through the second fluidic channel, the mixing feature of the third fluidic channel providing randomized arrangement of particles flowing through the third fluidic channel.

170. The method of any of claims 154 through 169, further comprising capturing images of particles as the particles are conveyed along the outlet channel.

171. The method of claim 170, further comprising classifying the particles by analyzing the captured images.

172. The method of claim 171, further comprising sorting particles from the outlet channel in response to classifying or identifying the particles by analyzing the captured images.

173. The method of claim 172, sorting particles including activating one or more valves to redirect fluid flow from the outlet channel to another outlet channel selected from a plurality of other outlet channels.

174. The method of any of claims 154 through 173, the particles including biological cells.

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