Patent Publication Number: US-2023140317-A1

Title: Measuring deformability of a cell

Description:
BACKGROUND 
     Cellular mechanical properties may be indicative of various diseases states. For example, a change in the deformability of red blood cells is an early indication of sepsis as well as hereditary disorders such as spherocytosis, elliptocytosis, ovalocytosis, and stomatocytosis, metabolic disorders such as diabetes, hypercholesterolemia, and obesity, as well as other disorders such as adenosine triphosphate-induced membrane changes, oxidative stress, and paroxysmal nocturnal hemoglobinuria. A change in red blood cell deformability is also associated with malaria, sickle cell anemia, and myocardial infarction. As a further example, change in deformability of white blood cells has also been associated with sepsis. 
     Rheological phenotyping, or the characterization of the deformability of cells, allows for detection of various diseases. In cancer research, elasticity of circulating tumor cells is strongly correlated the metastatic potential of the cells, with more elastic cells having higher metastatic potential. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    illustrates an example method for measuring deformability of a cell, consistent with the present disclosure. 
         FIG.  2    illustrates an example apparatus for measuring deformability of a cell, consistent with the present disclosure. 
         FIG.  3    further illustrates an example apparatus for measuring deformability of a cell, consistent with the present disclosure. 
         FIG.  4    further illustrates a side profile of a portion of an example apparatus for measuring deformability of a cell, consistent with the present disclosure. 
         FIGS.  5 A and  5 B  illustrate example apparatuses for measuring deformability of a cell, consistent with the present disclosure. 
         FIG.  6    further illustrates an example apparatus for measuring deformability of a cell, consistent with examples of the present disclosure. 
         FIG.  7    further illustrates an example apparatus for measuring deformability of a cell, consistent with examples of the present disclosure. 
         FIG.  8    illustrates an example apparatus for measuring deformability of a cell including barriers to contain a cell, consistent with examples of the present disclosure. 
         FIGS.  9 A and  9 B  illustrate example apparatuses for measuring deformability of a cell including non-mechanical mechanisms to contain a cell, consistent with examples of the present disclosure. 
         FIG.  10    illustrates an example apparatus for measuring deformability of a cell, consistent with the present disclosure. 
         FIG.  11    illustrates an example apparatus for measuring deformability of a cell, consistent with the present disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific examples in which the disclosure may be practiced. It is to be understood that other examples may be utilized, and structural or logical changes may be made without departing from the scope of the present disclosure. The following detailed description, therefore, is not to be taken in a limiting sense, and the scope of the present disclosure is defined by the appended claims. It is to be understood that features of the various examples described herein may be combined, in part or whole, with each other, unless specifically noted otherwise. 
     Biological cells are the basic building blocks of skin, tissues, and other materials. Cells and their organelles are enveloped by thin membranes that separate their chemical contents from the extracellular environment. Biological membranes are supramolecular assemblies composed of a lipid double layer with embedded and adsorbed membrane proteins. Each monolayer of the membrane consists of billions of adjacent lipid molecules, which are composed of two hydrophobic tails and a hydrophilic headgroup. The two monolayers taken together, facing each other with the hydrophobic tails, serve as a barrier of 4-10 nm thickness, which exhibits a partial permeability to some small hydrophobic and polar molecules. 
     Cell deformation and mechanical property analysis may allow for rheological phenotyping. For instance, cells may be brought into an apparatus and deformed. The flow may be driven by external pumps, and the deformation of the cell may be observed via a high-speed camera. The deformation is obtained later by post-processing. Post-processing of a large number of optical images takes a significant amount of time. Moreover, these devices are not able to sort the cells, as they cannot operate in real time. Furthermore, these devices take hours to process a large amount of cells (such as greater than 10{circumflex over ( )}6 cells) and are poorly amenable to point-of-care instrument solutions. 
     Measuring deformability of a cell, consistent with examples of the present disclosure, may include isolating a cell in a cell probing chamber, and measuring deformability of the cell with either integrated optics or an external imaging system. By applying a standing pressure wave to the cell within the cell probing chamber, an imaging system that operates at relatively low speed, such systems that capture approximately 10 frames per second (fps), may be used rather than relatively higher speed imaging systems, such as those that capture approximately 1000 fps or more. By allowing for slower fps imaging systems to be used, the cost for conducting rheological phenotyping may be reduced, and analytic rheological phenotyping may be performed on a single cell at a time. 
     An example method for measuring deformability of a cell, consistent with the present disclosure, includes detecting a single cell of a biologic sample in a cell probing chamber of a microfluidic device. The method includes isolating the cell in the cell probing chamber of the microfluidic chip by terminating the flow of the biologic sample through the microfluidic chip. The method further includes causing deformation of the cell by introducing ultrasonic waves (e.g., standing waves) into the cell probing chamber and measuring deformability of the cell responsive to the introduction of the ultrasonic waves. 
     In additional examples of the present disclosure, an apparatus for measuring deformability of a cell includes a fluidic channel actuated by a set of fluidic pumps. The apparatus may further include a cell probing chamber to hold a single cell from a biologic sample for deformation testing. The apparatus may further include an ultrasound source to perform deformation testing on the cell by applying a pressure field to the cell in the cell probing chamber. In various examples, the apparatus includes a lateral fluidic channel and a longitudinal fluidic channel disposed orthogonal to the lateral fluidic channel. Each of the lateral fluidic channel and the longitudinal fluidic channel are actuated by a different respective set of fluidic pumps. In such examples, the apparatus includes a cell probing chamber disposed at an intersection of the lateral fluidic channel and the longitudinal fluidic channel. 
     In yet a further example, an apparatus for measuring the deformability of a cell, consistent with the present disclosure, includes a lateral fluidic channel and a longitudinal fluidic channel disposed orthogonal to the lateral fluidic channel. Each of the lateral fluidic channel and the longitudinal fluidic channel are actuated by a different respective set of fluidic pumps. The apparatus may further include a cell probing chamber disposed at an intersection of the lateral fluidic channel and the longitudinal fluidic channel. The cell probing chamber may hold a single cell from a biologic sample for deformation testing. Moreover, the apparatus may include an ultrasound source to perform deformation testing on the cell by applying a pressure field to the cell in the cell probing chamber, and a plurality of channels fluidically coupled to the cell probing chamber to sort cells after deformation testing. 
     Turning now to the Figures,  FIG.  1    illustrates an example method  100  for measuring deformability of a cell, consistent with the present disclosure. At  101 , the method  100  includes detecting a single cell of a biologic sample in a cell probing chamber of a microfluidic device. As discussed further herein, flow within the microfluidic device may be controlled using a plurality of pumps, and an imaging system may be used to visualize cells within the microfluidic device. The microfluidic chip includes a channel that is actuated by a set of pumps. In various examples, the microfluidic chip may include a cross-channel which is actuated in two directions by an independent set of pumps. In the flow direction, flow is provided either on-chip or off-chip by traditional pumps. Once a cell is identified within the microfluidic device, the pumps may stop pumping and therefore stop the flow of fluid through the microfluidic device. Accordingly, at  103 , the method  100  includes isolating the cell in the cell probing chamber of the microfluidic chip by terminating the flow of the biologic sample through the microfluidic chip. 
     At  105 , the method  100  further includes causing deformation of the cell by introducing ultrasonic waves into the cell probing chamber. For instance, an ultrasonic pressure field may be generated, such that the ultrasonic waves apply pressure on the isolated cell. In various examples, the microfluidic chip provides a structured pressure field by producing standing pressure-waves with micron-scale wavelengths. For instance, high-frequency piezo inkjet (PIJ) actuators may be fired simultaneously with semi-periodic pulses to create a standing pressure-wave in the chamber. Examples are not so limited, however, and in some examples, introducing ultrasonic waves includes generating an ultrasonic pressure field using an ultrasonic transducer external to the microfluidic device. In such examples, the method may include focusing the ultrasonic waves using an ultrasonic horn, and delivering the focused ultrasonic waves to a via opening in the microfluidic device. 
     As discussed further herein, the microfluidic chip may include a transparent surface that allows imaging, such as by epi-illumination microscopy. Accordingly, at  107  the method  100  includes measuring deformability of the cell responsive to the introduction of the ultrasonic waves. For instance, the method may include measuring the width and/or length of the cell before application of the ultrasonic waves, and measuring the width and/or length of the cell during application of the ultrasonic waves. 
     In various examples, the method  100  may include releasing the cell from the cell probing chamber by asymmetrically activating a plurality of fluidic pumps in the microfluidic device. 
       FIG.  2    illustrates an example apparatus  202  for measuring deformability of a cell, consistent with the present disclosure. The apparatus  202  is capable of performing the method  100  illustrated in  FIG.  1   . For instance, the apparatus  202  is capable of detecting a single cell  209  of a biologic sample in a cell probing chamber  211  of a microfluidic device  202 . A biologic sample may flow through channel  213  in the direction of the arrows. As discussed further herein, the fluid flow may be induced using internal pumps and/or external pumps. Accordingly, the cell  109  may be isolated in the cell probing chamber  211  of the microfluidic chip  202  by terminating or reducing the flow of the biologic sample through the microfluidic chip  202 . While complete flow termination may be difficult to achieve, significant reduction of the flow rate (or slow down of the flow) may enable enough time for deformation analysis to be performed. In some examples, a pulsatory flow might be used to move cells with deformation analysis during flow pause. 
     As discussed with regards to  FIG.  1   , the microfluidic chip  202  may cause deformation of the cell  201  by introducing ultrasonic waves into the cell probing chamber  211 . More specifically, a standing pressure-wave field may be generated between PIJ actuators  217 - 1  and  217 - 2  fired at a frequency in the gigahertz range. As the standing pressure wave applies pressure on the cell  201 , the deformability of the cell  201  may be measured (e.g., responsive to the introduction of the ultrasonic waves). To view the cell  201  and measure the deformability, the microfluidic chip  202  may include integrated optics and/or an external imaging system. The integrated optics may include lenses, such as micro-lenses packaged with the microfluidic chip, or flat-lenses which are fabricated directly or packaged with the microfluidic capping layer, or imaged through lens-less computational microscopy. 
     Although  FIG.  2    illustrates a cross-shaped microfluidic device, examples are not so limited. For instance, in various examples, the apparatus includes a fluidic channel, with fluidic pumps disposed on opposing ends to control the flow of a biologic sample therethrough. The apparatus may further include an ultrasound source to perform deformation testing, as discussed herein. The ultrasound source may be an external ultrasound source to generate a standing wave within the fluidic channel, or the ultrasound source may be an integrated ultrasound source to generate the standing wave. As an illustration, the fluidic channel may be a channel with an input and an output on a side opposing the input. The biologic sample may flow along an axis from the input to the output. A PIJ actuator, or a plurality of PIJ actuators may be disposed within the fluidic channel. For instance, a PIJ actuator may be disposed within the fluidic channel and arranged to generate a standing wave traversing the axis of the fluid flow. Additionally and/or alternatively, a plurality of PIJ actuators may be disposed within the fluidic channel and arranged to generate the standing wave traversing the axis of the fluid flow. 
       FIG.  3    further illustrates an example apparatus  202  for measuring deformability of a cell, consistent with the present disclosure. More particularly,  FIG.  3    illustrates the apparatus  202  with a coupled ultrasound controller  219 , and an external imaging system. As illustrated, the ultrasound controller  219  may be coupled to PIJ actuators  217 - 2  and  217 - 1 . The ultrasound controller  219  may coordinate the simultaneous firing of the PIJ actuators  217 - 2  and  217 - 1  with semi-periodic pulses as to create a standing pressure-wave in the chamber  211 . In some examples, the ultrasonic waves may be generated using an ultrasonic pressure field using an ultrasonic transducer external to the microfluidic device  202 . Accordingly, in some examples, the apparatus includes a plurality of piezoelectric actuators disposed on opposing ends of a lateral fluidic channel (e.g., channel  215  illustrated in  FIG.  2   ). The ultrasound controller  219  may be communicatively coupled to the PIJ actuators  217 - 2  and  217 - 1  (e.g., coupled to the ultrasound source) to control a frequency of the ultrasound waves applied to the cell (e.g.,  201  illustrated in  FIG.  1   ). 
     Also as illustrated in  FIG.  3   , the apparatus  202  includes an imagining system. For instance, as illustrated in  FIG.  3   , the imaging system may include an image sensor  223 , which may be a charge-couple device (CCD), a complementary metal-oxide-semiconductor (CMOS) imaging device, or any other suitable imaging sensor. The imaging system may further include a light source  225 , a dichroic mirror  227 , and an objective  221  to visualize the cell  201 . 
       FIG.  4    further illustrates a side profile of a portion of an example apparatus  402  for measuring deformability of a cell, consistent with the present disclosure. More particularly,  FIG.  4    illustrates the apparatus  402  with an external ultrasonic wave source. As illustrated in  FIG.  4   , an ultrasonic pressure field may be generated using an external ultrasonic transducer  429 - 1  and  429 - 2 . The pressure wave from the ultrasonic transducer may be focused using an ultrasonic horn  431 - 1  and  432 - 2  to intensify the pressure wave. 
     The intensified pressure wave may be delivered to a small via opening, also referred to herein as a coupling port, in the microfluidic chip. For instance, box  433  illustrates an exploded view of a portion of the microfluidic chip  402 . As illustrated in  FIG.  4   , the ultrasound horn  431  may deliver the intensified pressure wave to the via  435 . As used herein, the via  435  refers to or includes a channel traversing a silicon top-layer  439  of the microfluidic chip  402 . The via  435  is fluidically coupled with the cell probing chamber  411  and does not extend into a base-layer  441  of the microfluidic chip  402 . The base-layer  441  may comprise SU-8 or other suitable components. The via is filled with an aqueous solution which we use to probe our cells. 
     In various examples, the via  435  may be filled with an aqueous solution. The interface between this aqueous solution and the silicon in layer  439  is an interface with a strong difference in wave speed. Thus, the via  435  etched in silicon  439  acts as a waveguide conveying the pressure wave into the cell probing chamber  411 . 
       FIGS.  5 A and  5 B  illustrate example apparatuses for measuring deformability of a cell, consistent with the present disclosure. More particularly,  FIGS.  5 A and  5 B  illustrate additional examples of providing ultrasound waves. As illustrated in  FIG.  5 A , an apparatus  502  for measuring deformability of a cell may include a lateral fluidic channel  515  and a longitudinal fluidic channel  513  disposed orthogonal to the lateral fluidic channel  515 . Fluid, including a biologic sample, may be input at fluidic input  543 , flow through the apparatus  502  in the direction of the arrow, and exit the apparatus  502  at the fluidic output  545 . 
     In some examples, the flow of fluid is controlled by integrated fluidic pumps. For instance, fluidic pumps may be disposed within channel  515  and within channel  513  (not illustrated in  FIG.  5 A ). The flow within the apparatus  502  may be controlled by individually actuating different fluidic pumps. For instance, to induce flow from fluidic input  543  to fluidic output  545 , fluidic pumps near fluidic input  543  may be actuated. To reverse the flow and/or slow the flow of fluid from fluidic input  543  to fluidic output  545 , fluidic pumps near fluidic output  545  may be actuated. To stop the flow of fluid, all fluidic pumps may cease firing. 
     As illustrated in  FIG.  5 A , piezoelectric elements  517 - 1  and  517 - 2  may be disposed on opposing sides of the lateral fluidic channel  515 . As discussed herein, the piezoelectric elements  517 - 1  and  517 - 2  may create a standing wave within the cell probing chamber  511 . In various examples, fluidic pumps may also be disposed within fluidic channel  515 . For instance, a fluidic pump (not illustrated) may be disposed near piezoelectric element  517 - 1 , and another fluidic pump (not illustrated) may be disposed near piezoelectric element  517 - 2 . Firing of pumps within fluidic channel  515  may direct a cell along channel  515  between piezoelectric element  517 - 1  and piezoelectric element  517 - 2 . For instance, in additional examples, a cell may be released from the cell probing chamber  511  by asymmetrically activating a plurality of fluidic pumps in the microfluidic device  502 . In some examples, the integrated fluidic pumps may be thermal inkjet (TIJ) ejectors, among other examples. Additionally and/or alternatively, an external pump or external pumps may be used to induce a fluid flow in the microfluidic device  502 . 
     Each of the lateral fluidic channel  515  and the longitudinal fluidic channel  513  may be actuated by a different respective set of fluidic pumps. The cell probing chamber  511  may be disposed at an intersection of the lateral fluidic channel  515  and the longitudinal fluidic channel  513 . As described herein, the cell probing chamber  511  may hold a single cell from a biologic sample for deformation testing. An ultrasound source may allow for perform deformation testing on the cell by applying a pressure field to the cell in the cell probing chamber  511 . For instance, piezoelectric elements  517 - 1  and  517 - 2  may actuate so as to form a standing wave within cell probing chamber  511 . An integrated imaging system and/or an external imaging system may allow for the imaging and measurement of deformation of the cell, responsive to application of the standing wave. 
       FIG.  5 B  further illustrates an example apparatus  504  including an external ultrasound generator. As illustrated in  FIG.  5 B , waveguide channels  547 - 1  and  547 - 2  may be fluidically coupled to the ends of channel  515 . Each of waveguide channels  547 - 1  and  547 - 2  may be coupled to an ultrasound generator  549 . The ultrasound waves generated by the ultrasound generator  549  may travel through the waveguide channels  547 - 1  and  547 - 2  and generate a standing wave in the cell probing chamber  511 . 
       FIG.  6    further illustrates an example apparatus  602  for measuring deformability of a cell, consistent with examples of the present disclosure. As illustrated in  FIG.  6   , a plurality of channels  651 - 1  and  651 - 2  may be fluidically coupled to the cell probing chamber  611  to sort and concentrate cells after deformation testing. For instance, as the properties of the cell  601  are determined, one of a plurality of pumps  653 - 1  and  653 - 1  may fire to pull the cell  601  into the associated channel,  651 - 1  or  651 - 2 , respectively. As an example, if a deformability of the cell  601  is detected to be above a particular threshold, then the cell  601  may be drawn into channel  651 - 1  by firing pump  653 - 2  to push the cell  601  into channel  651 - 1 . Similarly, if a deformability of the cell  601  is detected to be below a particular threshold, then the cell  601  may be drawn into channel  651 - 2  by firing pump  653 - 1  to push the cell  601  into channel  651 - 2 . Additionally and/or alternatively, piezoelectric elements  617 - 1  and  617 - 2  may fire to push the cell  601  into channel  651 - 2  or channel  651 - 1 . Although  FIG.  6    illustrates two fluidic channels fluidically coupled to the cell probing chamber  611 , examples are not so limited, and any number of fluidic channels may be coupled to the cell probing chamber  611 . Multiple channels may be of particular interest for cell sorting and concentration in different cell collectors. 
       FIG.  7    further illustrates an example apparatus  702  for measuring deformability of a cell, consistent with examples of the present disclosure. Similar to  FIG.  6   , the apparatus  702  includes a plurality of channels  751 - 1  and  751 - 2  may be fluidically coupled to the cell probing chamber  711  to sort cells after deformation testing. For instance, as the properties of the cell  701  are determined, one of a plurality of pumps  753 - 1  and  753 - 1  may fire to pull the cell  701  into the associated channel,  751 - 1  or  751 - 2 , respectively. Additionally and/or alternatively, piezoelectric elements  717 - 1  and  717 - 2  may fire to push the cell  701  into channels  751 - 1  or  751 - 2 . Moreover, TIJ resistors  755 - 1  and  755 - 2  may be disposed adjacent to piezoelectric elements  717 - 1  and  717 - 2 . The TIJ resistors  755 - 1  and  755 - 2  may also be fired to direct the flow of the cell  701  into one of channels  751 - 1  or  751 - 2 . Although  FIG.  7    illustrates two fluidic channels fluidically coupled to the cell probing chamber  711 , examples are not so limited, and any number of fluidic channels may be coupled to the cell probing chamber  711 . 
       FIG.  8    illustrates an example apparatus  802  for measuring deformability of a cell including barriers to contain a cell, consistent with examples of the present disclosure. For instance, in various examples, apparatus  802  may include a barrier  857  to contain the cell  801 . Examples  857 - 1 ,  857 - 2 ,  857 - 3 ,  857 - 4  and  857 - 5  illustrate various designs of a barrier  857  that may be used. As illustrated, barrier  857 - 1  may include two pillars disposed orthogonal to the flow of the biologic sample to trap the cell  801  for measuring deformability. Once measurements are obtained, piezoelectric elements  817 - 1  and/or  817 - 2  may actuate to move the cell  801  around the barrier  857 - 1 . 
     As a further example, a pillar trap  857 - 2  may be disposed orthogonal to the flow of the biologic sample. Similar to the two pillars illustrated in  857 - 1 , the pillar trap  857 - 2  may include a plurality of vertically aligned pillars to trap the cell  801  for measuring deformability. Once measurements are obtained, piezoelectric elements  817 - 1  and/or  817 - 2  may actuate to move the cell  801  around the barrier  857 - 2 . 
     In yet another example, a funnel  857 - 3  may be disposed orthogonal to the flow of the biologic sample. The funnel  857 - 3  may include two tapered members, vertically aligned orthogonal to the flow of the biologic sample. The tapered members may trap the cell  801  for measuring deformability. Once measurements are obtained, piezoelectric elements  817 - 1  and/or  817 - 2  may actuate to move the cell  801  around the barrier  857 - 3 . 
     Furthermore, a depression  857 - 4  may be disposed orthogonal to the flow of the biologic sample. The depression  857 - 4  may include a recessed portion of the substrate and lid of the microfluidic device  802 . The depression  857 - 4  may trap the cell  801  for measuring deformability. Once measurements are obtained, piezoelectric elements  817 - 1  and/or  817 - 2  may actuate to move the cell  801  out of the depression  857 - 4 . 
     Yet further, a wall  857 - 5  may be disposed orthogonal to the flow of the biologic sample. The wall  857 - 5  may include a plurality of curved orthogonal pillars within the microfluidic device  802 . The wall  857 - 5  may be disposed orthogonal to the flow of the biologic sample and may trap the cell  801  for measuring deformability. Once measurements are obtained, piezoelectric elements  817 - 1  and/or  817 - 2  may actuate to move the cell  801  out of the depression  857 - 5 . 
     Although  857 - 1 ,  857 - 2 ,  857 - 3 ,  857 - 4 , and  857 - 5  illustrate different kinds of structures that can facilitate the trapping of the cell  801  in the cell probing chamber, different and/or additional barriers  857  may be used. In any scenario, the cell  801  may be released from the barrier  857  by reversing the flow momentarily and providing a lateral flow simultaneously by actuating the piezoelectric elements  817 - 1  and/or  817 - 2  in an asymmetric way, before re-establishing the flow in the direction illustrated. 
       FIGS.  9 A and  9 B  illustrate example apparatuses  902  for measuring deformability of a cell including non-mechanical mechanisms to contain a cell  901 , consistent with examples of the present disclosure. More particularly,  FIG.  9 A  illustrates an example apparatus  902  for measuring deformability of a cell including three-dimensional electrodes  961 - 1  and  961 - 2 , consistent with the present disclosure. Using a dielectrophoresis (DEP)-based cell-separation method, three-dimensional electrodes  961 - 1  and  961 - 2  may be disposed on the substrate of the microfluidic chip  902  and may hold the cell  901  at a point of high electric field gradient. Accordingly, in some examples, the apparatus  902  may include a plurality of electrodes  961 - 1  and  961 - 2  disposed in a substrate of the cell probing chamber, the plurality of electrodes  961 - 1  and  961 - 2  to hold the cell  901  in the cell probing chamber by dielectrophoresis. 
     Similarly,  FIG.  9 B  illustrates an example apparatus  902  for measuring deformability of a cell including a laser beam gradient  963 , consistent with the present disclosure. In such examples, the laser beam gradient  963  may be created by a laser optical system. The laser beam gradient  963  forms a single-beam gradient force trap to hold the cell  901  in the cell probing chamber. The cell  901  may be released from the cell probing chamber by terminating the electric field in  FIG.  9 A , or by terminating the laser beam gradient in  FIG.  9 B . 
       FIG.  10    illustrates an example apparatus  1002  for measuring deformability of a cell, consistent with the present disclosure. As illustrated in  FIG.  10   , a plurality of diagonal channels  1071 - 1 ,  1071 - 2 ,  1071 - 3 ,  1071 - 4 ,  1071 - 5 ,  1071 - 6 ,  1071 - 7 , and  1071 - 8  (referred to collectively as diagonal channels  1071 ) may be fluidically coupled to the cell probing chamber. Each diagonal channel  1071  may further include a piezoelectric element  1073 - 1 ,  1073 - 2 ,  1073 - 3 ,  1073 - 4 ,  1073 - 5 ,  1073 - 6 ,  1073 - 7 , and  1073 - 8  (referred to collectively as piezoelectric elements  1073 ). The piezoelectric elements  1073  may provide a variety of combinations for generating a standing ultrasound wave, and/or provide a variety of combinations for moving the cell  1001  through the apparatus  1002 . For instance, a subset of the piezoelectric elements  1073  may be selected for firing to create the standing ultrasound wave. Additionally and/or alternatively, a subset of the piezoelectric elements  1073  may be selected for moving the cell  1001  into channels  1051 - 1  or  1051 - 2 . Moreover, pumps  1053 - 1  and/or  1053 - 2  may assist in directing the flow of the cell  1001  into a respective channel. 
       FIG.  11    illustrates an example apparatus  1102  for measuring deformability of a cell, consistent with the present disclosure. Particularly,  FIG.  11    illustrates an apparatus  1102  including an integrated optics system. As illustrated in  FIG.  11   , the apparatus  1102  may include a lateral fluidic channel  1115 , a longitudinal fluidic channel  1113 , and a cell probing chamber  1111 . The cell probing chamber  1111  may include a transparent lid  1175  disposed over a base substrate  1177  to form a channel  1179  therethrough. An integrated lens  1181  may be disposed on the transparent lid  1175  of the cell probing chamber  1111 . The integrated lens  1181  may focus light from the cell  1101  in the cell probing chamber  1111  to a sensor array  1183 . 
     The integrated lens  1181  could comprise a plurality of materials. For instance, the integrated lens  1181  could comprise a zone plate, a Fresnel lens, metasurfaces, or other suitable lenses and/or micro-lenses for a variety of imaging modalities and optical configurations (e.g., infinity corrected, point-to-point magnification, integrated source, fluorescence, etc.). If a flat lens is used, the sensor can be in close proximity to the channel and substrate to create a compact package. 
     Although specific examples have been illustrated and described herein, a variety of alternate and/or equivalent implementations may be substituted for the specific examples shown and described without departing from the scope of the present disclosure. This application is intended to cover any adaptations or variations of the specific examples discussed herein. Therefore, it is intended that this disclosure be limited only by the claims and the equivalents thereof.