Patent Publication Number: US-2020300235-A1

Title: Peristaltic pump with two-part fluid chamber and associated devices, systems, and methods

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present application claims priority to and the benefit of U.S. Provisional Patent Application No. 62/819,905, filed Mar. 18, 2019, the entirety of which is incorporated by reference in its entirety. 
    
    
     TECHNICAL FIELD 
     The present disclosure relates generally to devices and methods for pumping fluids from a patient and/or delivering pharmaceutical agents to a patient, including peristaltic pump assemblies implantable in a patient for relieving intraocular pressure. 
     BACKGROUND 
     Intraocular pressure (IOP) quantifies the pressure of the aqueous humor inside the eye. Many individuals suffer from disorders, such as glaucoma, that cause chronic heightened IOP. Over time, heightened IOP can cause damage to the optical nerve of the eye, leading to loss of vision. Presently, treatment of glaucoma mainly involves periodically administering pharmaceutical agents to the eye to decrease IOP. These drugs can be delivered by, for example, injection or eye drops. However, the effectiveness of pharmaceuticals can vary greatly from patient-to-patient. Furthermore, effective treatment of glaucoma requires adherence to rigid dosage schedules that can be difficult to follow for some patients. 
     Another way IOP can be reduced is by removing some of the fluid from inside the patient&#39;s eye. However, current devices are not suitable or practical for therapeutic use. For example, current devices do not simultaneously satisfy the desire for small size, low power, and a lifetime of many years before failure. Thus, there remains a need for wearable fluid displacement devices that meet requirements for safety and reliability while being as cost-effective as possible. 
     SUMMARY 
     The present disclosure advantageously describes peristaltic pump assemblies configured to pump fluid from a patient and/or deliver pharmaceutical agents to the patient. In some embodiments, a pump assembly can include a compressing member and a round fluid chamber comprising a hard outer portion and a flexible membrane coupled to the hard outer portion. The compressing member is controlled by a motor to rotate along a circumference to compress the fluid chamber in a circular motion, thereby pumping a fluid through the fluid chamber. The two-part construction of the fluid chamber can decrease the amount of stress experienced by the flexible membrane, thereby increasing the longevity of the fluid chamber. 
     In one embodiment, a peristaltic pump assembly includes a fluid chamber comprising a fluid channel configured to allow a fluid to pass therethrough, the fluid chamber including a hard outer portion comprising a bell-shaped groove on an inner surface of the hard outer portion and a flexible membrane attached to the hard outer portion and extending over the inner surface of the hard outer portion, wherein the bell-shaped groove and the flexible membrane define the fluid channel, and a roller coupled to the fluid chamber and configured to deform the flexible membrane against the bell-shaped groove on the inner surface of the hard outer portion to collapse the fluid channel. 
     In some embodiments, the flexible membrane and the bell-shaped groove of the hard outer portion are configured such that a maximum stress experienced by the flexible membrane while being deformed against the bell-shaped groove is below a fatigue limit of the flexible membrane. In some embodiments, the flexible membrane comprises a thickness between 25 um and 150 um. In some embodiments, the thickness of the flexible membrane is 50 um. According to some aspects, the roller comprises a fillet radius that is less than a radius of the bell-shaped groove. In some embodiments, a thickness of the flexible membrane is less than the fillet radius of the roller. In some embodiments, the flexible membrane is attached to the hard outer portion by an adhesive. In one aspect, the flexible membrane is attached to the hard outer portion by a laser weld. In another aspect, the flexible membrane is formed to include a camber. In still another aspect, the flexible membrane comprises silicone rubber. In some embodiments, the hard outer portion comprises an annular shape. 
     In some embodiments, the bell-shaped curve comprises at least one of a Gaussian curve, a symmetric spline, a sinusoidal curve, or a mirrored biarc. In some embodiments, the bell-shaped curve comprises an inflection point between a concave portion of the bell-shaped curve and a convex portion of the bell-shaped curve. In some embodiments, the flexible membrane further includes a coating positioned over an outer face of the flexible membrane, wherein a coefficient of friction of the coating is less than a coefficient of friction of the outer surface of the flexible membrane. 
     According to another embodiment of the present disclosure, a method of assembling a peristaltic pump assembly includes assembling a fluid chamber, wherein assembling the fluid chamber comprises: providing a hard outer portion comprising a bell-shaped groove on an inner surface of the hard outer portion; and attaching a flexible membrane to the hard outer portion such that the flexible membrane extends over the inner surface of the hard outer portion, and such that the flexible membrane and the bell-shaped groove of the hard outer portion define a fluid channel; and coupling a roller assembly comprising a roller to the fluid chamber such that the roller is configured to pass over the flexible membrane to deform the flexible membrane against the bell-shaped groove of the hard outer portion. 
     In some aspects, the flexible membrane and the bell-shaped groove of the hard outer portion are configured such that a maximum stress experienced by the flexible membrane while being deformed against the bell-shaped groove is below a fatigue limit of the flexible membrane. In some embodiments, the method further includes forming a roller fillet comprising a fillet radius that is less than a radius of the bell-shaped groove. In some embodiments, attaching the flexible membrane to the hard outer portion comprises attaching the flexible membrane to the hard outer portion using an adhesive. In some embodiments, attaching the flexible membrane to the hard outer portion comprises attaching the flexible membrane to the hard outer portion using a laser weld. In some embodiments, the method further includes forming the flexible membrane to include a camber. 
     In some embodiments, the bell-shaped curve comprises at least one of a Gaussian curve, a symmetric spline, a sinusoidal curve, or a mirrored biarc. In some embodiments, the bell-shaped curve comprises an inflection point between a concave portion of the bell-shaped curve and a convex portion of the bell-shaped curve. In some embodiments, the flexible membrane further includes a coating positioned over an outer face of the flexible membrane, wherein a coefficient of friction of the coating is less than a coefficient of friction of the outer surface of the flexible membrane. 
     According to another embodiment of the present disclosure, a peristaltic pump assembly comprises an annular fluid chamber comprising a hard ring comprising a concave groove on an inner surface of the hard ring and a membrane attached to the hard ring and extending over the inner surface of the hard ring to form a fluid channel comprising a curved cross-section, and a roller assembly coupled to the fluid chamber comprising a roller configured to deform the membrane against the concave groove on the inner surface of the hard ring to collapse the fluid channel. 
     In some embodiments, the membrane and the concave groove of the hard ring are configured such that a maximum stress experienced by the membrane while being deformed against the concave groove is below a fatigue limit of the membrane. In some embodiments, at least a portion of the concave groove comprises a circular arc. 
     Additional aspects, features, and advantages of the present disclosure will become apparent from the following detailed description. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Illustrative embodiments of the present disclosure will be described with reference to the accompanying drawings, of which: 
         FIG. 1  is a diagrammatic view of a micropump system, according to an embodiment of the present disclosure. 
         FIG. 2  is a diagrammatic schematic view of a micropump assembly, according to an embodiment of the present disclosure. 
         FIG. 3  is a perspective view of a driver assembly and fluid chamber of a micropump assembly, according to an embodiment of the present disclosure. 
         FIG. 4  is a perspective view of a micropump assembly, according to an embodiment of the present disclosure. 
         FIG. 5  is a cross-sectional perspective view of a fluid chamber of a micropump assembly, according to an embodiment of the present disclosure. 
         FIG. 6  is a perspective view of a driver assembly of a micropump assembly, according to an embodiment of the present disclosure. 
         FIG. 7  is a cross-sectional perspective view of the driver assembly of  FIG. 6 , according to an embodiment of the present disclosure. 
         FIG. 8  is a diagrammatic schematic view of a driver circuit and fluid chamber of a micropump assembly, according to an embodiment of the present disclosure. 
         FIG. 9  is a diagrammatic schematic view of a micropump assembly, according to an embodiment of the present disclosure. 
         FIG. 10  is a diagrammatic schematic view of a micropump assembly, according to an embodiment of the present disclosure. 
         FIG. 11  is a cross-sectional diagrammatic view of a fluid chamber assembly in an uncompressed position, according to an embodiment of the present disclosure. 
         FIG. 12  is a cross-sectional diagrammatic view of a fluid chamber assembly being compressed by a roller, according to an embodiment of the present disclosure. 
         FIG. 13  is a graphical view of a fluid chamber assembly being compressed by a roller, according to aspects of the present disclosure. 
         FIG. 14  is a graphical view of a fluid chamber assembly being compressed by a roller, according to aspects of the present disclosure. 
         FIG. 15  is a plot of a fatigue strength curve of a flexible material, according to aspects of the present disclosure. 
         FIG. 16  is a table showing force, stress, and energy results of a fluid chamber compression simulation, according to aspects of the present disclosure. 
         FIG. 17  is a cross-sectional view of a fluid chamber assembly being compressed by a roller, according to an embodiment of the present disclosure. 
         FIG. 18  is a cross-sectional view of a fluid chamber assembly being compressed by a roller, according to an embodiment of the present disclosure. 
         FIG. 19  is a cross-sectional view of a membrane of a fluid chamber assembly deforming as a result of fluid pressure within the fluid chamber, according to aspects of the present disclosure. 
         FIG. 20  is a cross-sectional view of a fluid chamber assembly that includes a flexible membrane having a negative camber, according to one embodiment of the present disclosure. 
         FIG. 21  is a flow diagram illustrating a method of assembling fluid chamber, according to one aspect of the present disclosure. 
         FIG. 22  is a flow diagram illustrating a method for pumping fluid from a patient&#39;s eye, according to an embodiment of the present disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     For the purposes of promoting an understanding of the principles of the present disclosure, reference will now be made to the embodiments illustrated in the drawings, and specific language will be used to describe the same. It is nevertheless understood that no limitation to the scope of the disclosure is intended. Any alterations and further modifications to the described devices, systems, and methods, and any further application of the principles of the present disclosure are fully contemplated and included within the present disclosure as would normally occur to one skilled in the art to which the disclosure relates. For example, while the therapeutic devices are described in terms of eye-mountable devices configured to pump fluid (e.g., aqueous humor) from a human eye, it is understood that it is not intended to be limited to this application. The devices and systems are equally well suited to any application requiring pumping of fluids. In particular, it is fully contemplated that the features, components, and/or steps described with respect to one embodiment may be combined with the features, components, and/or steps described with respect to other embodiments of the present disclosure. For the sake of brevity, however, the numerous iterations of these combinations will not be described separately. 
     Presently, treatment of glaucoma mainly consists of periodically administering pharmaceutical agents to the eye to decrease IOP. These drugs can be delivered by, for example, injection or eye drops. However, the effectiveness of pharmaceuticals can greatly vary from patient-to-patient. Furthermore, effective treatment of glaucoma requires adherence to rigid dosage schedules that can be difficult to follow for some patients. 
     Another way to reduce IOP involves removing quantities of fluid from inside the patient&#39;s eye. However, current devices are not suitable or practical for therapeutic use. For example, devices to remove fluid from the eye need to be small enough to be implanted into the patient at a practical location, such as the patient&#39;s eye cavity. Due to the invasiveness of implanting such a device, the device should be able to operate independently for a period of time. Thus the device must be able to operate efficiently in a restricted space, and must be reliable enough to require little or no maintenance. The present disclosure proposes implantable peristaltic micropump assemblies for pumping fluid from inside a patient&#39;s eye. 
     A peristaltic pump acts by radially compressing a tube with one or more rotating rollers. This permits a fluid to be pumped without the fluid contacting any portion of the pump mechanism, other than the tube itself. The tube is disposable, such that when the fluid begins to undergo a physical change (e.g., coagulation) or a chemical change (e.g., oxidation), or when a different fluid is desired to be pumped, a fresh tube may be inserted into the pump to prevent contamination. Often these tubes are made of silicone, although other materials may be used. 
     Traditional peristaltic pumps suffer from fatigue and lifetime problems. In order to prevent backward leakage of fluids that would decrease the pump&#39;s efficiency, it is desirable to crush the tube completely, so that its inner walls touch and gaps between the walls are minimized or eliminated. This creates substantial stress on the edges of the tube, such that after repeated cycling the tube material experiences fatigue-related failures. Such failures are typically prevented by replacing the tube before fatigue sets in. 
     Traditional peristaltic pumps also require substantial power to operate, as the majority of the energy consumed by the pump is expended crushing the tube (deformation energy), and only a fraction goes toward moving the fluid forward. For peristaltic pumps powered by rechargeable batteries, this leads to short battery life and frequent recharging. With the addition of an induction coil, batteries can be charged by wireless induction, such that there is no need to connect a physical charging cable. 
     Energy consumption of a peristaltic pump can be reduced by reducing the thickness of the tube walls. However, this increases stress on the tube walls and therefore decreases the lifespan of the tube. Furthermore, because flexible plastic or rubber tubing is formed by extrusion of a cylindrical member with a cylindrical hole along its longitudinal axis, there is a practical limit to how thin tube walls can be made for micropump applications. These and other limitations have prevented traditional peristaltic pumps from being used in implantable medical devices, as the replacement of tubes would require surgical removal and replacement of the device, and even with inductive charging a short battery lifetime makes the devices prohibitively inconvenient to use in vivo. 
     The present disclosure describes micropump assemblies that overcome the challenges described above. In that regard, the micropump assemblies described herein provide advantageous arrangements of components and features that allow the micropumps to reliably and efficiently pump fluid from a patient&#39;s eye while maximizing the lifetime of the device. 
       FIG. 1  is a diagrammatic view of a micropump system  100 , according to one embodiment. The system  100  includes an eye-mountable micropump  110  coupled to an eye  55  of a patient  50 , and a wireless transmission device  150  configured to wirelessly transmit electrical power  152  and/or electrical signals to the micropump  110 . The micropump  110  is sized and shaped to be permanently or semi-permanently attached to the patient&#39;s eye  55 . In particular, the micropump  110  is configured to be positioned within an ocular cavity proximate the eye  55 . In some embodiments, the micropump  110  can be positioned at different locations with respect to the patient&#39;s eye, such as below the eye  55 , above the eye  55 , inside the eye  55 , or inside any suitable anatomical structure that allows the micropump to pump fluid from the eye  55 . 
     Because the micropump  110  may not be easily accessible for charging or reprogramming, the micropump  110  is configured to wirelessly receive electrical power  152  and/or electrical signals from the wireless transmission device  150 . The wireless transmission device  150  includes circuitry and components to send electrical power, such as coils, transformers, power supplies, batteries, or other circuitry. Additionally, the wireless transmission device  150  can include wireless communication components to transmit and/or receive data in the form of wireless signals to/from the micropump  110 . As explained further below, the micropump  110  can also include wireless electronic components for receiving electrical power and/or electrical signals form the transmission device  150 . The micropump  110  can include a battery and a processing component that allow it to operate independently for a period of time (e.g., days, weeks, months) without receiving power or signals from the transmission device  150 . 
       FIG. 2  is a diagrammatic schematic view of a micropump assembly  110 , according to one embodiment of the present disclosure. The micropump assembly  110  includes a compressible fluid chamber  120  and a driver assembly  130  configured to compress the fluid chamber  120  to move fluid through the fluid chamber  120 . The driver assembly  130  is actuated and controlled by a plurality of electronic and mechanical components, such as an application-specific integrated circuit (ASIC)  112 , an actuator or motor  114 , a gear box  116 , and a power circuit  118 . The power circuit  118  includes a battery  117 , and a coil  119  configured to receive electrical power from a wireless source, such as the wireless transmission device  150  shown in  FIG. 1 . The power circuit  118  is configured to supply electrical power to the components of the micropump  110 , including the ASIC  112 , and the motor  114 . The power circuit  118  separately provides electrical power to the ASIC  112  and the motor  114 , in some embodiments. In other embodiments, the power circuit  118  provides electrical power to the ASIC  112 , which distributes the electrical power to the other components of the micropump assembly  110 , including the motor  114 . 
     The ASIC  112  is configured to control an output of the motor  114 , thereby controlling the performance (e.g., flow rate) of the micropump  110  assembly. The ASIC  112  operates according to a protocol, which comprises computer code instructions saved in a memory device of the ASIC  112 . The protocol is defined by one or more parameters, such as time, number of cycles, physiological measurements, battery life, etc. Thus, the ASIC  112  is configured to control operation of the micropump assembly  110  while the assembly  110  is implanted in the patient. It will be understood that, although the ASIC  112  is shown as a single component in  FIG. 2 , the micropump assembly  110  may comprise a plurality of individual integrated circuits or other circuitry that is configured to carry out the functions of the assembly  110 . 
     The power circuit  118  and/or the ASIC  112  provide electrical power to the motor  114 , which is configured to activate the driver assembly  130  via the gear box  116 . The gear box  116  is configured to modify or convert a torque provided by the motor  114 , and apply the modified torque to the driver assembly  130 . In that regard, the gear box  116  comprises one or more gears or stages of gears to increase or decrease the torque applied by the motor  114 . Thus, the gear box  116  can also be appropriate referred to as a torque converter. In an exemplary embodiment, the gear box  116  is configured to increase the torque applied by the motor  114 . The increased torque provided by the gear box  116  can help to overcome friction on the driver assembly  130  caused by, e.g., the roller  134  on the compressible fluid chamber  120 . 
     In an exemplary embodiment, the motor  114  is an electrostatic motor, such as the Silmach PowerMEMS® electrostatic motor. However, other motors are also contemplated by the present disclosure, including lavet-type motors, piezoelectric motors, step motors, brushless motors, or any other suitable type of motor. 
     The driver assembly  130  includes a drive shaft  132  configured to rotate about a first axis and a compressing member or roller  134  rotatably coupled to the drive shaft  132  by a rotor  136 . The rotor  136 , which can also be referred to as a crank, couples the roller  134  to the drive shaft  132  such that the roller  134  travels about the first axis of the drive shaft  132  along a circumference  131  or circular path when the drive shaft  132  is rotated by the motor  114  via the gear box  116 . The roller  134  is rotatably coupled to the rotor  136 , such that the roller can rotate about a second axis while traveling along the circumference  131 . As described further below, the drive shaft  132  and roller  134  can each comprise one or more ball bearings, such as the drive shaft bearing  137 , to reduce friction, and therefore reduce the amount of torque required to rotate the driver assembly  130 . 
     As the driver assembly  130  rotates the roller  134  along the circumference, the roller compresses the fluid chamber  120  in a circular motion around the circumference  131 . This circular compression causes the peristaltic pumping action that moves fluid into the fluid chamber  120  through an inlet  126 , through the fluid chamber  120  in the circumferential direction  131 , and out the fluid chamber  120  through an outlet  128 . As an example, when the micropump assembly  110  is implanted onto the patient&#39;s eye  55 , the inlet  126  can be coupled the eye  55  to receive the aqueous humor, and the outlet  128  can be positioned outside the eye  55 , for example, in the ocular cavity. When the micropump assembly  110  is activated, the micropump  110  draws the fluid from inside the eye  55 , and expels the fluid outside of the eye  55 , thereby reducing the patient&#39;s intraocular pressure (IOP). 
     The fluid chamber  120  can include a round outer portion, or ring  122 , and a flexible membrane  124  coupled to the hard outer ring  122  and opposing an inner surface of the outer ring  122 . The outer ring  122  can comprise a material that is relatively harder and/or more rigid than the flexible membrane, such as a plastic. As will be explained further below, compression of the fluid chamber  120  involves deforming the membrane  124  toward the outer ring  122  to close or restrict a channel formed between the outer ring  122  and the membrane  124 . As will be understood with reference to the embodiment of  FIG. 2 , the outer ring  122  is not necessarily circular. For example, in  FIG. 2 , the outer ring  122  includes a circular arc portion and a linear portion. In that regard, the outer ring  122  is not closed, but forms a U-shape. Thus, although the term “ring” is used with respect to the outer portion or ring  122 , this is in no way limiting to closed, circular shapes. 
     The components of the micropump assembly  110 , including the driver assembly  130 , fluid chamber  120 , ASIC  112 , motor  114 , gear box  116 , and power supply circuit  118  are coupled to and/or contained within a housing  140 . The housing  140  is sized and shaped to be implanted into an ocular cavity of the patient  50 . The housing  140  is configured to contain and protect the components of the micropump assembly  110  from physical and/or chemical damage. In some embodiments, the housing  140  provides a waterproof casing for one or more electrical components of the device, such as the ASIC  112 , the power circuit  118 , and the motor  114 . The housing  140  may also be configured to protect one or more components from chemical damage. In some embodiments, the housing  140  is configured to protect the mechanical components, such as the gear box  116  and the driver assembly  130  from foreign material that could interfere with or inhibit the mechanical performance of the micropump  110 . 
       FIG. 3  is a perspective view of a drive assembly and fluid chamber  120  of the micropump assembly  110 , according to one embodiment. As in the embodiment shown in  FIG. 2 , the embodiment of  FIG. 3  includes a drive shaft  132  and a roller  134  rotatably coupled to the drive shaft  132  by the rotor or crank  136 . The roller  134  is configured to travel in a circular motion about a first axis of the drive shaft  132 . The fluid chamber  120  includes a hard outer ring  122 , and a flexible membrane  124  opposing an inner face or surface of the outer ring  122 . An inlet  126  and an outlet  128  of the fluid chamber  120  are integrally formed with the outer ring  122  and are configured to direct ingress and egress of fluid through the fluid chamber  120 . However, in other embodiments, the inlet  126  and/or outlet  128  are not integrally formed with the outer ring  122 . For example, the inlet  126  and/or outlet  128  can be formed of the membrane  124 , or formed of both the membrane  124  and the outer ring  122 . In other embodiments the inlet  126  and/or outlet  128  can comprise physically separate components that are attached to the outer ring  122  and/or the membrane  124 . As described above, as the roller  134  rotates about the circumference  131 , the membrane  124  is deformed or pressed against the outer ring  122  to move fluid through the fluid chamber  120  in a peristaltic motion toward the outlet  128 . To reduce friction, the roller  134  is also configured to rotate or spin in a planetary motion about a second axis and around the first axis. Further, in some embodiments, 
       FIG. 4  is a perspective view of a micropump assembly  110 , according to an embodiment of the present disclosure. Similar to the assembly  110  shown in the  FIG. 2 ,  FIG. 4  shows a driver assembly  130  and a fluid chamber  120  contained within a housing  140 . In contrast to the embodiments shown in  FIGS. 2 and 3 , the rotor or crank  136  shown in  FIG. 4  has a circular shape and is positioned around the drive shaft  132 . The circular rotor  136  couples the roller  134  to the drive shaft  132  such that the roller  134  travels around the first axis along a circumference. 
     The assembly  110  includes a housing  140  that houses the components of the assembly  110 , including the driver assembly  130  and the fluid chamber  120 . Other components are also positioned within the housing, such as the ASIC  112 , motor  114 , gear box  116 , power circuit  118 , or any other suitable components. The housing  140  shown in  FIG. 4  includes multiple pieces, including a first piece  141  and a second piece  143 . The second piece  143  may act as a cover for one or more components such as the gear box  116  and the motor  114 . The housing  140  is configured to contain the components of the assembly  110  within a space small enough to be implanted into the patient. In that regard, the assembly  110  comprises a length  144 , a width  146 , and a height  148 . In an exemplary embodiment, the length  144  is about 9 mm, the width  146  is about 9 mm, and the height  148  is about 2 mm. However, the dimensions can be modified as appropriate for the application. For example, the length  144 , width  146 , and/or height  148  can range from less than 1 mm to more than 30 mm. 
       FIG. 5  is a perspective cross-sectional view of the fluid chamber  120  of the assembly  110 . The fluid chamber  120  includes an outer ring  122 , and a flexible membrane  124  coupled to the outer ring  122  to define a fluid channel  125 . The flexible membrane  124  comprises an elastomeric material such as silicone, while the outer ring  122  comprises a relatively harder material, such as a plastic. The membrane  124  is positioned over, or opposing, an inner surface  121  of the outer ring  122 . The inner surface  121  comprises a valley that partially defines the fluid channel  125 . The membrane  124  is attached to the outer ring  122  at a first groove  127   a  on a top side of the outer ring  122 , and a second groove  127   b  on an opposing bottom side of the outer ring  122 . A first ridge  129   a  of the membrane  124  is positioned within the first groove  127   a , and a second ridge  129   b  of the membrane  124  is positioned within the second groove  127   b . The first and second ridges  129   a ,  129   b  can be attached to the outer ring  122  by any suitable method, including a weld, thermal bond, adhesive, or a mechanical fit (e.g., interference fit). It will be understood that, in some embodiments, the first and second ridges  129   a ,  129   b , are formed of opposing edges of a rectangular membrane. 
     As explained above, the outer ring  122  may comprise a material that is relatively harder and/or more rigid than the membrane  124 . Accordingly, while the membrane  124  is configured to be deformed by the roller  134 , the outer ring  122  may be configured to retain its shape, even with applied pressure from the roller  134 . In a relaxed or undeformed state, the membrane  124  spans across the curved inner surface  121  of the outer ring  122  such that a space exists in the fluid channel  125  for a fluid to pass through. When the roller  134  passes over the membrane  124 , the membrane  124  is deformed toward the inner surface  121  of the outer ring  122  to reduce or close the space in the fluid channel  125 . The membrane  124  is thus deformed in a circular fashion around the circumference to create a peristaltic pumping action that moves a fluid through fluid chamber  120  toward the outlet  128 . 
     The fluid chamber  120  described above exhibits certain advantages to existing fluid chambers. For example, the coupling of the membrane  124  to the hard outer ring  122  can reduce the stress applied to the fluid chamber  120  when compressed by the driver assembly  130 . In that regard, as opposed to flexible tubes that are compressed by collapsing one side of the tube toward the other side of the tube, compressing the fluid chamber  120  shown in  FIG. 5  is accomplished by deforming the flexible membrane against the relatively hard or rigid outer ring  122 . Thus, when the membrane  124  is relaxed, the channel  125  of the fluid chamber  120  between the membrane and the outer ring  122  is relatively unrestricted. Compressing the membrane  124  against the outer ring  122  can be achieved with relatively little stress to any given portion of the flexible membrane  124 . Furthermore, because the outer ring  122  provides the structural integrity to define the channel  125 , the flexible membrane can be formed of a soft elastomeric material that can be more easily compressed. Furthermore, the smooth, round surface  121  can also reduce the amount of stress on the membrane  124  during compression. Thus, the fluid chamber  120  can be compressed with less resistance than what would be required with flexible tubing. Furthermore, because the membrane  124  undergoes relatively little stress, the durability and lifespan of the fluid chamber  120  can be increased. 
       FIGS. 6 and 7  depict a driver assembly  130  of the micropump assembly  110  shown in  FIG. 4 , according to one embodiment of the present disclosure. In particular,  FIG. 6  is a perspective view of the driver assembly  130 , and  FIG. 7  is a perspective cross-sectional view of the driver assembly  130  taken along the line  7 - 7 . As in  FIG. 4 , the driver assembly  130  includes a drive shaft  132  and a rotor or crank  136 , which comprises a top plate  136   a  and a bottom plate  136   b . The driver assembly  130  also includes a gear  138  fixedly coupled to the top plate  136   a  and bottom plate  136   b  of the rotor by a rotor pin  136   c . The gear  138  is positioned concentrically with the drive shaft  132  and the first axis. The pin  136   c  couples the gear to the rotor such that torque applied to the gear  138  rotates the rotor  136 , and therefore the roller  134 . The drive shaft  132  is concentrically coupled to a first bearing  137  to rotate about a first axis. Similarly, the roller  134  comprises a bearing concentrically coupled to a roller bearing pin  133  to rotate about a second axis. 
     Because it is desired that the entire micropump assembly  110  is sized and shaped to be implanted into a patient (e.g., inside the ocular cavity), the components of the driver assembly  130  can be low-profile. For example, in some embodiments, the ball bearings of the drive shaft  132  and the roller  134  have a diameter of 2 mm or less. 
       FIG. 8  is a top view of a driver assembly and a fluid chamber  120 , according to one embodiment of the present disclosure. The driver assembly  130  of  FIG. 8  may include similar or identical components as the assembly  130  shown in  FIGS. 2 and 3 , such as a drive shaft  132 , a crank  136 , and a roller  134 . The fluid chamber  120  includes a circular portion  120   a  and a non-circular portion or spiral portion  120   b . In that regard, the non-circular portion  120   b  is shaped and arranged such that a radius  123  between the drive shaft  132  and the fluid chamber increases in a clockwise direction of the fluid chamber  120 . Thus, with the configuration shown in  FIG. 8 , the micropump assembly  110  can function as a pump over the circular portion  120   a , and as a flow controller for the rest of the cycle over the non-circular portion  120   b . In that regard, as the roller  134  passes over the circular portion  120   a , the fluid chamber  120  is fully compressed, but when the roller  134  passes over the non-circular portion  120   b , the fluid chamber  120  is only partially compressed, thereby reducing the hydraulic resistance as the roller  134  rotates clockwise over the non-circular portion  120   b . When a positive pressure gradient exists across the micropump  110  (e.g., when the IOP is relatively high), fluid may flow from the inlet  126  to the outlet  128  even without pumping. In this case, pumping is mainly used for clearing and preventing clogs. When a stepper motor is used as the actuator or motor  114 , the motor  114  can be controlled to stop at any desired angular location. Thus, the stepper motor  114  can control the roller  134  to stop at a desired position along the non-circular portion  120   b . Because the compression of the fluid chamber  120  by the roller  134  gradually decreases as the roller  134  moves clockwise along the non-circular portion  120   b , the micropump  110  can act as a variable flow controller to adjust the flow of fluid through the micropump  110  that is caused by the positive pressure gradient. For example, if the motor  114  stops the roller  134  over the circular portion  120   a , the fluid chamber  120  is fully compressed such that flow through the fluid chamber  120  is effectively zero. By contrast, when the roller  134  is moved to a location along the non-circular portion  120   b  that is near the outlet  128 , the fluid chamber  120  may not be compressed at all, or only minimally compressed, such that fluid flow through the chamber  120  is effectively unrestricted. The motor  114  can also control the roller  134  to stop at a desired location along the non-circular portion  120   b  corresponding to a desired amount of compression of the fluid chamber  120 , and therefore adjusting the flow of fluid through the chamber  120  to a desired amount. 
       FIG. 9  is a diagrammatic schematic view of a micropump assembly  110 , according to another embodiment of the present disclosure. The micropump assembly  110  embodiment shown in  FIG. 9  can include similar or identical components as the embodiment shown in  FIG. 2 . For example, the embodiment shown in  FIG. 9  includes an ASIC  112 , a motor  114 , a gear box  116 , a power circuit  118 , a fluid chamber  120 , and a driver assembly  130 . Additionally, the micropump assembly  110  includes a rotary encoder  160  in communication with the motor  114 , a pressure sensor  170 , and a rotor spring  139 . The rotary encoder  160  is communicatively coupled to the motor  114  and configured to provide an indication or feedback to indicate the rotational position of the motor  114  to the ASIC  112  and/or motor  114 . The rotary encoder  160  can be used to control pumping of fluid through the micropump  110  with volumetric precision. For example, in some embodiments, the micropump assembly  110  can be used to deliver pharmaceutical agents to the patient. The rotary encoder  160  can be used to provide feedback to the ASIC  112  to control dosing of the pharmaceutical with nanoliter precision. 
     The pressure sensor  170  measures a pressure or pressure gradient across the fluid chamber  120 . The pressure sensor  170  is communicatively coupled to the inlet  126  of the fluid chamber  120  to measure a fluid pressure from a source, such as the IOP of the patient&#39;s eye  55 . The pressure sensor  170  provides signals to the ASIC  112  representative of a measured fluid pressure. The ASIC  112  adjusts performance of the micropump  110  based on the feedback provided by the pressure sensor  170 . For example, as IOP fluctuates throughout the day, the ASIC  112  may control the micropump  110  to pump relatively greater volumes of fluid during portions of the day when the IOP measured by the pressure sensor  170  is relatively high. By contrast, the ASIC  112  may control the micropump  110  to pump relatively smaller volumes of fluid, or cease pumping altogether, during portions of the day when the IOP measured by the pressure sensor  170  is relatively low. In this manner the pressure sensor  170  and the ASIC  112  function as a pressure controller. For example, the ASIC  112  can be programmed to maintain the IOP, as measured by the pressure sensor  170 , at a desired pressure. 
     The driver assembly  130  includes a rotor spring  139  positioned between the drive shaft  132  and the roller  134 . The spring  139  can be biased to push the roller  134  toward the fluid chamber  120 . In that regard, the spring  139  can regulate the force applied by the roller  134  on the membrane  124  of the fluid chamber  120 . The spring  139  of the rotor  136  may also exhibit a particular amount of travel, thereby adjusting the radius or distance between the roller and the drive shaft  132 . The spring  139  can comprise one or more of a variety of mechanisms to impart a spring force, including compression springs, membranes, magnets, leaf springs, torsion springs, coil springs, or any other suitable type of spring. 
       FIG. 10  depicts another embodiment of the micropump assembly  110  that is used for delivering a pharmaceutical agents to the patient. The micropump assembly  110  includes a reservoir  119  containing the pharmaceutical agent, with the reservoir  119  in communication with the inlet  126  of the fluid chamber  120 . It will be understood that the driver assembly  130  of the embodiment in  FIG. 10  is shown rotating in a counter-clockwise fashion toward the outlet  128 . The outlet can be connected to or otherwise in fluid communication with an anatomical structure of the patient, such as an organ (e.g., the eye) or a tissue. The micropump assembly  110  shown in  FIG. 10  includes a rotary encoder  160  in communication with the ASIC  112  and the motor  114 . The rotary encoder  160  can be used as described above to precisely control the volumetric flow of the pharmaceutical agent into the patient via the outlet  128 . In some embodiments, the motor  114 , rotary encoder  160 , and ASIC  112  are configured to enable microdosing of the pharmaceutical agent with nanoliter precision. 
     As mentioned above, embodiments of the present disclosure include fluid chambers having a two-part construction with a bell-shaped fluid channel instead of an extruded flexible tube with a circular cross-section.  FIGS. 11 and 12  show diagrammatic cross-sectional views of a fluid chamber  320  including a bell-shaped fluid channel, according to aspects of the present disclosure. The cross-sectional views shown in  FIGS. 11 and 12  are exemplary of the cross section of the fluid chamber  120  shown in  FIG. 2 , with membrane  324  as an exemplary embodiment of the membrane  124 , and the hard outer ring  322  as an exemplary embodiment of the hard outer ring  122 . The fluid chamber  320  includes a hard outer portion or ring  322  having a bell-shaped groove  321  or channel on its inner surface, with a flexible membrane  324  (e.g., a TPE or silicone membrane) sealed across its top by means of adhesives or welding (e.g., laser, ultrasonic, or thermal welding), forming an enclosed channel with a roughly D-shaped or bell-shaped cross section. The membrane  324  may have a C-shaped cross section that extends over the edges of the hard plastic outer ring, and may be held in place by an adhesive to hard outer ring  322 , although this is not required, as laser welding may produce very thin, strong weld lines that seal the membrane  324  across the trough or channel of the hard outer ring  322 , forming the bell-shaped channel or fluid chamber. Both the hard outer ring  322  and the flexible membrane  324  may be fabricated by injection molding, although the membrane  324  may more easily be fabricated by extrusion. 
     The curved inner surface  321  between outer inflection points  344  can be defined by one or more types of curves. For example, in the embodiment of  FIG. 11 , a portion of the curved inner surface  321  is defined by a circle of radius R. The curved surface  321  changes from a circular profile to an inflected arcuate profile at inner inflection points  346 . The curved surface  321  is centered and symmetrical about a center line or plane  342 . As explained further below, in one embodiment, the radius R of the curved surface  321  can be equal to or approximately equal to the radius r of the roller fillet  334  plus the thickness d of the membrane  324 . In some embodiments, the curved surface  321  between outer inflection points  344  can be defined by other types of curves, such as a sinusoidal, Gaussian, Lorentzian, Voigt, symmetrical spline, mirrored biarc, etc. For example, in one embodiment, at least a portion of the curved surface  321  between outer inflection points  344  can be represented by a Gaussian function of the form: 
     
       
         
           
             
               f 
                
               
                 ( 
                 x 
                 ) 
               
             
             = 
             
               a 
                
               
                 e 
                 
                   
                     - 
                     
                       x 
                       2 
                     
                   
                   
                     2 
                      
                     
                       b 
                       2 
                     
                   
                 
               
             
           
         
       
     
     Where a is related to the height of the curve&#39;s peak and b is related to the width of the bell-shape. In other embodiments, at least a portion of the curved surface  321  can be represented by a sinusoidal function, wherein the outer inflection points are aligned with consecutive troughs of the sin wave. In some aspects, one or more of the inflection points can be positioned between a convex portion of the curved surface  321  and a concave portion of the curved surface  321 . In other embodiments, at least a portion of the curved surface  321  can be defined by one or more of: a parabola, hyperbola, ellipse, spiral, a polynomial curve, exponential curve, sigmoid, or any other suitable type of curve. 
     Similarly, the cross-sectional shape or profile of the roller fillet  334  can be made to be geometrically compatible with the curved surface  321 . For example, in some embodiments, the roller fillet  334  and the curved surface  321  are defined by the same type of curve such that the roller fillet  334  can more evenly distribute force on the membrane  324  to deform against the curved surface  321  of the hard outer ring  322 . 
     Referring to  FIG. 12 , in operation, the membrane  324  is compressed by a roller mechanism  334  to contact the bell-shaped groove  321  on the inner surface of the hard outer ring  322 . According to at least one embodiment of the present disclosure, the roller  334  is a wheel bearing with a plastic fillet, over-molding, or cover, and power is transferred from the motor to the roller  334  with minimal friction by means of a motor gear to which the bearing is attached via a pin although other mechanical or electromechanical transmission mechanisms may be employed to achieve the desired result. The roller  334  or roller fillet comprises a rounded cross section with a curvature characterized by the fillet radius r. The hard outer ring  322  may be annular or substantially circular in shape or may have other shapes, such as a spiral or hybrid of spiral and circular. 
     The two-part construction of the fluid chamber  320  can decrease the maximum stress experienced by the membrane  324  during compression. For example, the membrane  324  may experience significantly less stress during compression than conventional flexible tubing. The reduction in maximum membrane stress has a nonlinear beneficial effect on the endurance or cycle lifetime of the membrane  324 , and therefore on the lifetime of the peristaltic pump with D-shaped or bell-shaped channel. 
     Flexible materials such as silicone rubber exhibit a “fatigue limit”, wherein repeated stresses above this limit lead to substantially reduced endurance (measured in flexure cycles), whereas repeated stresses below this limit degrade the material much less, and the material is thus able to survive many more cycles. In that regard,  FIGS. 13 and 14  are diagrammatic graphical views of the displacement (in um) and stress (in MPa) experienced by the flexible membrane  324  during compression by a roller  334 . It will be understood that  FIGS. 13 and 14  show only half of the cross-section of the fluid chamber  320  during compression. 
     In  FIG. 13 , a graphical view of the displacement of the membrane  324  is shown while the membrane  324  is fully compressed by the roller  334 . The displacement is highest at the bottom of the bell-shaped groove of the hard outer ring  322 , and lowest at the top of the bell-shaped groove, which is near the location at which the membrane  324  is attached to the hard outer ring  322 .  FIG. 14  shows a graphical map of the stress experienced by the membrane  324  during maximum compression. The stress may be highest at the regions of greatest curvature, including near the top or shoulder  325  of the bell-shaped curve, and at the bottom  327  of the bell-shaped curve. In this configuration, the maximum stress experienced by the membrane  324  during compression is approximately 0.7 MPa. However, the maximum stress may be higher or lower is some configurations, such as when the thickness of the membrane  324  increases, or when the radius R of the bell-shaped groove decreases. 
     The lifespan of the membrane  324 , measured in cycles, is a function of the maximum stress experienced by the membrane  324 .  FIG. 15  shows a representative rubber fatigue strength curve  400  for an example material, though not necessarily the exact curve for a given material used in the foregoing analysis. The fatigue limit of the material can be identified in the plot by the region of the curve with the most gradual slope. By maintaining the maximum stress of a material below this fatigue limit, the number of cycles the material can endure before failure increases exponentially. 
     As can be seen in the plot  400 , the effect of stress on the endurance or cycle life of the example material is small when the stress is substantially above the fatigue limit, such that a stress reduction of 1 MPa may increase the endurance of the example material by only approximately 100 thousand cycles. When the stress on the example material is substantially below the fatigue limit, the effect of stress on the endurance or cycle life of the example material is greatly increased, such that a stress decrease of 1 MPa may increase the endurance of the example material by hundreds of millions of cycles. There is typically a transition region near the fatigue limit, where the sensitivity of the material changes rapidly. 
     A person of ordinary skill in the art, after becoming familiar with the teachings herein, will recognize that a reduction of membrane stress from, for example, 2.1 MPa for a circular tube to 0.8 MPa for a two-part fluid chamber as described above may be sufficient to maintain the maximum stress below the membrane material&#39;s fatigue limit, such that the resulting increase in endurance or cycle life is disproportionate and nonlinear, and such that an endurance in excess of 300 million cycles may be achievable. For an implantable micropump operating at one cycle per second, an endurance on the order of 300 million cycles equates to a life of approximately 10 years, which may not be achievable using a traditional, tube-based peristaltic pump design. Reduced membrane stress also broadens the range of available membrane materials that can be used. 
     The maximum force on the membrane (and therefore the energy or power requirement for the device) declines as the membrane thickness is decreased. Thus, one may infer that it would be desirable to use a membrane that is as thin as possible in order to increase efficiency of the micropump. However, simulation of an example peristaltic pump with bell-shaped channel for an example glaucoma-mitigating implantable micropump yields unexpected results with regard to maximum stress on the membrane (and therefore its cycle lifetime), wherein a membrane thickness of about 50 um can provide an optimal thickness to maximize longevity of the membrane. As explained further below, the relative pressure (IOP) of the aqueous humor within the eye can be as high as about 9 kPa. This fluid pressure can cause the membrane to bulge outward, imparting stress on the membrane. The stress imparted by the 9 kPa of pressure from the eye on the membrane increases as the thickness of the membrane decreases. At a thickness of 50 um, the membrane  324  experiences an equal amount of stress from full compression by the roller  334 , and from the 9 kPa internal pressure of the aqueous humors of the eye. Decreasing membrane thickness below about 50 um shows no additional benefit, as the internal pressure of the aqueous humors of the eye becomes the dominant source of stress, exceeding the amount of stress experienced by the membrane  324  during full compression by the roller  334 . Flexible membranes of 50 um thickness can be reliably produced by extrusion. 
       FIG. 16  is a table that shows the results of different simulation parameters for the 2D and 3D simulation of an example peristaltic pump with bell-shaped channel implemented as an example glaucoma-mitigating implantable micropump. The 2D simulation results indicate that for the bell-shaped channel, the maximum stress on the membrane may be reduced by a factor of 2.0-3.8 vs. a traditional peristaltic pump with identical cross-sectional area. 2D results further indicate that the maximum membrane force may be reduced by a factor of 2.0-4.3, and energy or power requirement by a factor of 5.3-7.4, vs. a traditional peristaltic pump. In addition, the tube of a traditional peristaltic pump widens from 770 um to 830 um when fully compressed by the roller, whereas the width of the D-shaped or bell-shaped channel does not change, resulting in a more robust and less mechanically constrained design for the peristaltic pump with bell-shaped channel. 
     The 3D results from the table of  FIG. 16  indicate that the maximum stress on the membrane may be reduced by a factor of 2.0-2.6, and the maximum force may be reduced by a factor of 1.7-2.1 vs. a traditional peristaltic pump. If ratios of energy savings and force reduction are roughly consistent between the 2D and 3D results, then the energy requirement of the peristaltic pump with bell-shaped channel may be reduced by a factor of approximately 4, and likely not less than a factor of 2, vs. a traditional peristaltic pump. After becoming familiar with the teachings herein, a person of ordinary skill in the art will recognize that with traditional, tube-based peristaltic pump designs, it is not possible to adjust design parameters to reduce the maximum tube stress, maximum tube force, and energy requirement simultaneously, while maintaining a consistent flowrate for the pump. The person of ordinary skill in the art will further recognize that the hereinabove demonstrated reductions in membrane stress and power requirement represent a qualitative rather than incremental improvement in the performance of peristaltic pumps for long-life applications without tube replacement. 
     The peristaltic pump may be sized and/or shaped for a variety of different applications, both inside and outside the human body, and may exhibit a wide range of flow rates and capacities. However, according to at least one embodiment of the present disclosure, the peristaltic pump with bell-shaped channel includes a fluid channel cross-sectional area ranging between 0.03 mm 2  to 3 mm 2 , and supports a variable flowrate of between zero and about 6 microliters per minute, with a normal operating range of between zero and about 4.2 microliters per minute. In this example, continuous operation of the pump is preferred in order to prevent clogging of the drainage path, although ripples in the flow rate may be considered acceptable. 
     Furthermore, according to at least one embodiment of the present disclosure, the inlet operating pressure falls within a target range of 5-17 mmHg (0.67-2.27 kPa) with an ideal target of 12 mmHg (1.60 kPa), and a maximum range of 0-80 mmHg (0-10.67 kPa) while the outlet operating pressure falls within a normal expected operating range of 0-20 mmHg (0-2.67 kPa) and a maximum capacity of 70 mmHg (9.33 kPa). 
     According to at least one embodiment of the present disclosure, the maximum pressure gradient supportable by the peristaltic pump with bell-shaped cavity is −70 to 50 mmHg (−9.33 to 6.67 kPa), and the motor powering the pump mechanism is a MEMS electrostatic stepper motor (e.g., the Silmach PowerMEMS) capable of generating greater than 2.3 uNm of torque at 2.7 RPM or 373 uNm of torque at 1 revolution per hour, and with sufficient power and efficiency to drive the pump mechanism at the hereinabove stated pressures and flowrates without undue power consumption, such that a rechargeable battery of 200 uAh capacity can operate the device for at least one hour of continuous operation. In one example, the flexible membrane is made from biocompatible silicone rubber with a shore hardness of A50, a linear strain-stress curve at functional range, and a Young&#39;s modulus of 2 MPa, and the channel or fluid chamber formed between the membrane and the hard plastic ring is equal in cross-sectional area to a cylindrical tube with 300 um inner diameter. 
     According to at least one embodiment of the present disclosure, the total mechanism of the peristaltic pump with the bell-shaped channel that meets the exemplary criteria listed hereinabove, including a motor, gears, tube chamber, pressure sensor, housing, and wirelessly chargeable battery, is smaller than or equal to about 13 mm×13 mm×2 mm, with a preferred size of 9 mm×9 mm×&lt;2 mm. This is considered acceptable for use as a glaucoma-mitigating micropump that is implantable within the human ocular cavity. 
     According to at least one embodiment of the present disclosure, the bell-shaped channel is constructed from convex and concave circular curve segments having about the same radius of curvature, as this may simplify manufacturing, and also may also make the properties of the device easier to simulate through finite element modeling or other methods. 
     If the roller shape and size is not optimized for the size of the bell-shaped channel and membrane thickness, one or more gaps may form between the flexible membrane and the hard plastic channel when the membrane is maximally compressed by the rotating roller.  FIG. 17  is a cross sectional view of a portion of fluid chamber  320  that exhibits a gap between the membrane  324  and the bell-shaped groove  321  of the hard outer ring  322  when the membrane  324  is fully compressed by the roller  334 . This gap allows backward-leakage of fluid, reducing both the outlet pressure and the efficiency of the peristaltic pump. In order to prevent such gaps from forming, the roller fillet radius r must increase as a function of increasing channel width. In that regard,  FIG. 18  is a cross-sectional view of a portion of a fluid chamber  320  being compressed by a roller fillet  334  having a larger fillet radius than the roller fillet shown in  FIG. 17 . The radius of the roller fillet  334  is increased to better distribute pressure on the membrane  324  such that it contacts an entire surface of the bell-shaped groove  321 . For example, in one embodiment, an optimal roller fillet radius r is approximately equal to the radius of the bell-shaped groove  321  (R,  FIG. 11 ) less the thickness of the membrane  324  (d,  FIG. 11 ). In some embodiments, the optimal roller fillet radius r is slightly larger than the radius R of the bell-shaped groove  321  less the thickness d of the membrane  324 . It will be understood, however, that an oversized roller  334  is not desirable, as it increases both maximum stress and maximum force on the membrane material. Beyond a certain size, the roller  334  will no longer fit completely in the channel, which may also create a gap. 
     According to at least one embodiment of the present disclosure, an internal pressure within the peristaltic pump with a bell-shaped channel may cause the membrane  324  to bulge upward, as shown in  FIG. 19 . For example, a 9 kPa internal pressure of the aqueous humor within the human eye may cause a membrane of 50 um thickness to bulge upward by approximately 157 um, causing significant stress on the membrane material. According to at least one embodiment of the present invention, this bulge may be compensated for by manufacturing the membrane  324  with a sag or negative camber  329 , as shown in  FIG. 20 . This sag or negative camber  329  reduces the stress caused by internal pressure, but also reduces the cross-sectional area of the bell-shaped channel between the flexible membrane  324  and the hard outer ring  322 , thus reducing the capacity of the pump. A dome-shaped sag reduces the stress even further. A bulge or positive camber may also be designed into the flexible membrane  324  to increase the cross-sectional area of the bell-shaped channel, although this also increases the stress on the membrane material when the membrane  324  is compressed by the roller  334 . 
       FIG. 21  depicts a method  500  of assembling a peristaltic pump, according to embodiments of the present disclosure. In step  510 , a hard outer portion is provided that includes a bell-shaped groove on an inner surface of the hard outer portion. In some embodiments, the hard outer portion comprises a ring. The hard outer ring may comprise a plastic material, in some embodiments. Although referred to as a “ring,” the hard outer ring may not form a circle or closed shape. For example, the hard outer ring can be arranged in a U-shape, spiral shape, polygon, rectangle, or any other suitable shape. In some embodiments, at least a portion of the hard outer ring comprises an arcuate shape or profile, such as a segment of a circle. The hard outer ring may be provided by molding, extruding, machining, or any other suitable process. The bell-shaped groove may be formed during the extrusion or molding of the hard outer ring, or may be formed afterward by machining or any other suitable process. 
     In step  520 , a flexible membrane is provided. The flexible membrane comprises a flexible material such as silicone or TPE, and can be formed by extrusion, molding, or any other suitable process. The flexible membrane is formed to have a thickness appropriate for the application. For example, for a micropump, the thickness of the membrane can be very small (e.g., 25 um, 50 um, 75 um, 100 um, 150 um) in order to reduce the amount of force required to deform the membrane, thereby conserving electrical power. In one embodiment, a 50 um membrane is provided by an extrusion process to produce a flexible sheet of membrane material that can be wrapped around the inner surface of the hard outer ring. The hard outer ring may be flexible in at least one direction, but may be more hard and/or rigid than the membrane such that the hard outer ring experiences no deformation or negligible deformation when the membrane is deformed against the hard outer ring. 
     In step  530 , the flexible membrane is attached to the hard outer ring such that the flexible membrane extends over the inner surface of the hard outer ring. A bell-shaped fluid channel is created or defined by the flexible membrane and the bell-shaped groove of the hard outer ring. The flexible membrane may be attached to the hard outer ring by a laser weld, an adhesive, or any other suitable means of attachment. In one embodiment, the top and bottom surfaces of the hard outer ring comprise grooves inside of which the ends of the flexible membrane are positioned and attached. In other embodiments, the flexible membrane is attached to a flat surface of the hard outer ring, such as the top, bottom, and/or outer surface of the hard outer ring. 
     In step  540 , the fluid chamber formed by the flexible membrane and hard outer ring is coupled to a roller assembly. The roller assembly is coupled to the fluid chamber such that the roller is configured to move across the membrane of the fluid chamber to compress the membrane against the hard outer ring. In some embodiments, the roller assembly is configured to rotate about an axis to move the roller in a circular path. For example, the roller assembly can include a drive shaft and bearing centered around a central axis of the hard outer ring. 
       FIG. 22  depicts a method  600  of pumping a fluid (e.g., aqueous humor) from a patient&#39;s eye in order to reduce and/or regulate the patient&#39;s intraocular pressure (IOP). One or more steps of the method described can be carried out by a micropump assembly  110  as described above. In step  610 , a motor of a micropump is activated to actuate a pump mechanism comprising a compressing member and a compressible fluid chamber. The motor rotates the compressing member about an axis in a circular motion, with the compressing member compressing a membrane of the fluid chamber against a hard outer ring. The fluid chamber is in communication with the patient&#39;s eye such that the micropump displaces fluid from inside the eye to the exterior of the eye. In step  620 , the motor continues to rotate to pump a quantity of fluid from inside the eye, thereby reducing the IOP. The micropump may be controlled by an ASIC configured to control the output of the motor. The ASIC may control the output of the motor to displace a predetermined amount of fluid from the eye, to pump fluid at a predetermined flow rate, to operate the motor at a rotational speed, or some combination of these parameters. 
     In step  630 , the ASIC receives feedback from a pressure sensor and/or a rotary encoder, and in step  640 , the ASIC adjusts output of the motor based on the received feedback. For example, the feedback from the pressure sensor may include an electrical signal indicating a pressure measurement. The pressure sensor can be in fluid communication with an inlet of the fluid chamber to measure the fluid pressure from a source of the micropump, such as the patient&#39;s eye. The ASIC receives the pressure measurement and adjusts motor output according to a protocol. For example, the ASIC may be configured to execute computer instructions to maintain IOP at a particular pressure. When the pressure sensor measures a pressure that exceeds a threshold, the ASIC controls the motor to pump a particular quantity of fluid from the patient&#39;s eye. If the pressure measurement falls below a threshold, the ASIC does not activate the motor, or decreases the output of the motor. 
     In another example, the ASIC executes instructions to deliver an amount of a pharmaceutical agent to the patient. The ASIC activates the motor to rotate and receives feedback signals from the rotary encoder indicating the rotational position of the motor and compressing member. The ASIC controls the motor to rotate until the rotary encoder indicates that the motor is at a predetermined rotational position corresponding to an amount of pharmaceutical agent delivered to the patient. 
     In another example, the fluid chamber includes a circular portion and a non-circular portion, as described above. When a positive pressure differential is present across the fluid chamber (e.g., when IOP is relatively high), fluid may flow freely through the fluid chamber even without pumping. The motor and compressing member can be used to control the flow rate of fluid by controlling the motor to position the compressing member at a location on the non-circular portion that corresponds to a particular flow rate. To allow fluid to freely flow through the fluid chamber, the ASIC controls the motor to position the compressing member at a location on the non-circular portion at which the fluid chamber is least compressed, or uncompressed. To halt flow of fluid through the fluid chamber, the ASIC controls the motor to position the compressing member at a position along the circular portion of the fluid chamber such that the fluid chamber is fully compressed by the compressing member, thereby restricting flow of fluid through the fluid chamber. 
     In another example, the ASIC can include instructions to periodically pump fluid through the fluid chamber in order to prevent or remove clogs within the fluid chamber. For example, even when the IOP is below a threshold amount, or when a positive pressure gradient exists across the fluid chamber such that fluid is freely flowing without pumping, the ASIC may periodically activate the motor to compress the fluid chamber along its circumference to dislodge build-up of material and remove clogs. 
     It will be understood that various modifications can be made to the embodiments described above without departing from the material of the present disclosure. For example, although an ASIC is described as controlling the operation of the micropump assembly, other components and/or circuitry can be used to control operation of the micropump. For example, the micropump could include analog circuitry configured to control aspects of the micropump. The analog circuitry could function alone, or in combination with one or more microprocessors, field-programmable gate arrays (FPGA&#39;s), or any other appropriate analog or digital circuitry. Additionally, aspects of the different embodiments described above can be combined, even if the combinations are not explicitly shown in the drawings. For example, a micropump assembly can include a drug reservoir  119  as in  FIG. 10  and a pressure sensor as in  FIG. 9 , in some embodiments. In another embodiment, a micropump assembly can include a spring-loaded rotor  136  as in  FIG. 9  along with the drug reservoir  119  shown in  FIG. 10 . Additionally, any of the micropump assemblies described above can include a non-circular fluid chamber, as shown in  FIG. 8 . 
     The peristaltic pump may incorporate other components, including but not limited to gears, belts, additional rollers, an electrostatic motor, a pinch valve, a flow controller, a pressure sensor, a pressure regulator, one or more rotor bearings, an encoder, a microcontroller, and a motor coupling to drive the roller or rollers. The peristaltic pump may be a microelectromechanical systems (MEMS) device or incorporate MEMS components, or it may be a macroscopic device assembled from macroscopic components. 
     The ASIC can include one or more processing components and one or more memory components. The ASIC can be configured to execute computer code according to one or more programming protocols. In some example embodiments, one or more of the ASIC functions described above are executed by a computer program written in, for example, C, C Sharp, C++, Arena, HyperText Markup Language (HTML), Cascading Style Sheets (CSS), JavaScript, Extensible Markup Language (XML), asynchronous JavaScript and XML (Ajax), and/or any combination thereof. 
     Persons skilled in the art will recognize that the devices, systems, and methods described above can be modified in various ways not explicitly described or suggested above. Accordingly, persons of ordinary skill in the art will appreciate that the embodiments encompassed by the present disclosure are not limited to the particular exemplary embodiments described above. In that regard, although illustrative embodiments have been shown and described, a wide range of modification, change, and substitution is contemplated in the foregoing disclosure. It is understood that such variations may be made to the foregoing without departing from the scope of the present disclosure. Accordingly, it is appropriate that the appended claims be construed broadly and in a manner consistent with the present disclosure.