Abstract:
This disclosure relates to fluid line sets and related methods. In certain aspects, the fluid line sets include a vial adapter connected to a first end of a fluid line, and a cap removably attached to a second end of the fluid line such that the cap seals the second end of the fluid line. The vial adapter includes a base, a spike extending from a central region of the base, and a sidewall extending from the base and substantially surrounding the spike. The base and the side wall at least partially define a cavity configured to receive a portion of a vial. The cap includes a deformable portion at least partially defining a gas chamber, and the cap is configured so that deformation of the deformable portion causes gas to be forced from the gas chamber to the vial adapter via the fluid line.

Description:
TECHNICAL FIELD 
       [0001]    This disclosure relates to non-vented drug delivery. 
       BACKGROUND 
       [0002]    During hemodialysis, impurities and toxins are removed from the blood of a patient by drawing the blood out of the patient through a blood access site, typically via a catheter, and then passing the blood through an artificial kidney (often referred to as a “dialyzer”). The artificial kidney includes microtubes that each separate a first conduit from a second conduit. Generally, a dialysis solution (often referred to as a “dialysate”) flows through the first conduit of the dialyzer while the patient&#39;s blood flows through the second conduits of the dialyzer, causing impurities and toxins to be transferred from the blood to the dialysate through the microtubes. The impurities and toxins can, for example, be removed from the blood by a diffusion process. After passing through the dialyzer, the purified blood is then returned to the patient. 
         [0003]    When kidney failure is diagnosed, patients are typically given medication to help control the symptoms and slow the progress of damage to the kidneys. Patients with chronic kidney failure generally take drugs, such as iron supplements, to control the balance of minerals in the body. 
       SUMMARY 
       [0004]    In one aspect of the invention, a fluid line set includes a vial adapter having a base, a spike extending from a central region of the base, a sidewall extending from the base and substantially surrounding the spike, a fluid line having a first end connected to the vial adapter and a second end, and a cap removably attached to the second end of the fluid line such that the cap seals the second end of the fluid line. The base and the side wall at least partially define a cavity configured to receive a portion of a vial. The cap includes a deformable portion that at least partially defines a gas chamber. The cap is configured so that deformation of the deformable portion causes gas to be forced from the gas chamber to the vial adapter via the fluid line. 
         [0005]    In another aspect of the invention, a method includes causing gas to flow through a fluid line of a dialysis system until the gas enters a drug vial connected to a vial adapter assembly causing a pressure within the drug vial to increase, and clamping the fluid line after increasing the drug vial pressure. 
         [0006]    In yet another aspect of the invention, a dialysis system includes a dialysis machine including a blood pump and a drug pump, a blood line set including a blood line that can be operably connected to the blood pump and a drip chamber in fluid communication with the blood line, a fluid line set including a fluid line including a first end connected to a vial adapter and a second end, and a cap removably attached to the second end of fluid line such that the cap seals the second end of the fluid line. The cap includes a deformable portion at least partially defining a gas chamber. The cap is configured so that deformation of the deformable portion causes gas to be forced from the gas chamber to the vial adapter via the fluid line. 
         [0007]    Implementations can include one or more of the following features. 
         [0008]    In some implementations, the cap further includes a one-way valve. 
         [0009]    In certain implementations, the one way valve is disposed between the second end of the fluid line and the gas chamber to prevent fluid from passing into the gas chamber from the fluid line. 
         [0010]    In some implementations, the chamber includes a volume of sterile gas. 
         [0011]    In certain implementations, the sterile gas is air. 
         [0012]    In some implementations, the volume of sterile gas includes less than 2 ml of sterile gas. 
         [0013]    In certain implementations, the volume of sterile gas includes 1 to 2 ml of sterile gas. 
         [0014]    In some implementations, the fluid line includes a first end connected to the vial adapter and a second end and a cap removably attached to the second end of fluid line such that the cap seals the second end of the fluid line. The cap includes a deformable portion at least partially defining a gas chamber. The cap is configured so that deformation of the deformable portion causes gas to be forced from the gas chamber to the vial adapter via the fluid line. 
         [0015]    In certain implementations, the method includes fluidly connecting a drug vial with the fluid line via the vial adapter assembly. The vial adapter assembly includes a vial adapter having a spike extending from a central region of a base. 
         [0016]    In some implementations, the drug vial includes an initial internal pressure equal to an ambient pressure. 
         [0017]    In certain implementations, the drug vial includes an initial gas volume of 0.3 ml to 2 ml. 
         [0018]    In some implementations, the gas flowing through the delivery line introduces gas into the drug vial. 
         [0019]    In certain implementations, the gas volume within the drug vial is 2 ml to 3 ml. 
         [0020]    In some implementations, the introduced gas within the drug vial increases a pressure within the drug vial. 
         [0021]    In certain implementations, the method further includes removing the cap from the second end of the fluid line. 
         [0022]    In some implementations, the method further includes connecting the second end of the fluid line to an extracorporeal blood circuit. 
         [0023]    In some implementations, the method further includes delivering drug from the drug vial to the extracorporeal blood circuit via the drug delivery line. 
         [0024]    In certain implementations, the cap further includes a one-way valve. 
         [0025]    In some implementations, the one-way valve is disposed between the second end of the fluid line and the gas chamber to prevent fluid from passing into the gas chamber from the fluid line. 
         [0026]    In certain implementations, the chamber includes a volume of sterile gas. 
         [0027]    In some implementations, the sterile gas is air. 
         [0028]    In certain implementations, the volume of sterile gas includes less than 2 ml of sterile gas. 
         [0029]    In some implementations, the volume of sterile gas includes 1 to 2 ml of sterile gas. 
         [0030]    In some implementations, the dialysis system further includes a drug vial connected to the vial adapter, such that deformation of the deformable portion introduces causes gas to be forced into the drug vial. 
         [0031]    In certain implementations, the drug vial includes an initial gas volume of 0.3 to 2 ml. 
         [0032]    In some implementations, the additional gas increases the gas volume to 1 to 3 ml. 
         [0033]    Implementations can include one or more of the following advantages. 
         [0034]    The drug line sets described herein are designed to be used in medical systems, such as hemodialysis systems. Introducing air into the drug vials via the drug line sets of such systems decreases the vacuum pressure within the drug vial, which helps to ensure that the vacuum pressure generated within the drug line set by a pump exceeds the competing vacuum within the drug vial. This additional air improves the process of priming the system by helping to ensure that the desired amount of drug can be withdrawn from the drug vial. In addition, introducing additional air into the drug vial can account for air volume variations between drug vials of different manufacturers or manufacturing lots, which helps to expand the compatibility of the medical devices with a variety of drug vials without modifying any hardware components. Further, by introducing air into the drug vial via the drug delivery line set, both the drug delivery line and the additional air can be sterilized using a single sterilization process. 
         [0035]    Other aspects, features, and advantages will be apparent from the description and drawings, and from the claims. 
     
    
     
       DESCRIPTION OF DRAWINGS 
         [0036]      FIG. 1  is a front view of a hemodialysis machine including a drug delivery module mounted in a mid-section of the machine. 
           [0037]      FIG. 2  is an enlarged view of the midsection of the hemodialysis machine of  FIG. 1 . 
           [0038]      FIG. 3  is a perspective view of a drug delivery fluid line set including a vial spiking assembly and priming cap connected to a drug delivery line. 
           [0039]      FIG. 4A  is a perspective view of the drug delivery line set including the priming cap in the unactuated state and an enlarged view of the priming cap in an unactuated state. 
           [0040]      FIG. 4B  is a perspective view of the drug delivery line set including the priming cap in the actuated state and an enlarged view of the priming cap in an actuated state. 
           [0041]      FIG. 5  is an enlarged view of the drug delivery module of the hemodialysis machine of  FIG. 1  isolated from the hemodialysis machine. 
           [0042]      FIG. 6  is a perspective view of the vial spiking assembly and a spike cover. 
           [0043]      FIG. 7  is a perspective view of the drug delivery line set partially loaded into the drug delivery module. 
           [0044]      FIG. 8  is a perspective view of the drug vial being loaded onto the vial adapter. 
           [0045]      FIG. 9  is a perspective view of the drug delivery line set being loaded into a peristaltic pump of the drug delivery module. 
           [0046]      FIG. 10  is an enlarged view of the midsection of the hemodialysis machine of  FIG. 1  showing the drug delivery line set connected to the hemodialysis set prior to operating the pumps. Certain details of the hemodialysis machine have been omitted for simplicity. 
           [0047]      FIGS. 11A and 11B  are a perspective views of an alternative priming cap in the form of a dropper. 
       
    
    
     DETAILED DESCRIPTION 
       [0048]    Referring to  FIG. 1 , a hemodialysis system  100  includes a hemodialysis machine  102  having a drug delivery module  104  to which a drug delivery line set  106  is connected. The drug delivery module  104  and the drug delivery line set  106  can be used to deliver one or more drugs to a patient during hemodialysis treatment. Specifically, the drug can be delivered from a drug vial  108  through the drug delivery line set  106  to a drip chamber  110  of a blood line set  112  where the drug mixes with blood before the blood is returned to the patient. As will be described in detail below, a priming cap  116  (shown in  FIGS. 3, 4A, 4B, 5, and 11A and 11B ) of the drug delivery line set  106  includes a diaphragm that can introduce air into the drug vial  108  using a drug delivery line  140  of the drug delivery line set  106 . Introducing air into the drug vial  108  modifies the internal pressure within the drug vial  108  to ensure that the vacuum pressure within the drug delivery line  140 , throughout treatment, exceeds the competing vacuum within the drug vial  108 . 
         [0049]    Still referring to  FIG. 1 , the hemodialysis machine  102  includes a display  118  and a control panel  120 , whereby the user selections and instructions can be sent to, and stored by, a control unit of the hemodialysis machine  102 . The hemodialysis machine  102  also includes modules that house components used to perform hemodialysis, including the drug delivery module  104 , a blood pump module  122 , and a level detector module  124 . 
         [0050]    In use, the disposable blood line set  112 , which forms a blood circuit with the patient, is connected to the modules  104 ,  122 , and  124  on the front side of the hemodialysis machine  102 . During treatment, patient lines  126 ,  128  of the blood line set  112  are connected to the patient, and a pump tubing segment  130  of the blood line set  112  is connected to a blood pump  132  of the blood pump module  122 . As the blood pump  132  is operated, blood is drawn from the patient, pumped through a dialyzer  134  and the drip chamber  110  of the blood line set  112 , and then returned to the patient. 
         [0051]      FIG. 2  illustrates the mid-section of the hemodialysis machine  102  with the blood line set  112  and the drug delivery line set  106  connected to the modules  104 ,  122 , and  124  and with the drug vial  108  inserted into a vial adapter  136  of the drug delivery line set  106 . The blood line set  112  includes the pump tubing segment  130 , which is connected to the blood pump module  122  in a manner so as to operatively engage the blood pump  132  of the blood pump module  122 . Operation of the blood pump  132  pumps blood through the blood line set  112 . 
         [0052]    Still referring to  FIG. 2 , the drip chamber  110  of the blood line set  112  is positioned at a location downstream from the blood pump  132 . The drip chamber  110  permits gas, such as air, in the blood to escape from the blood before the blood is returned to a patient. The drip chamber  110  can be secured to the level detector module  124  so as to align with a fluid level detector  138  that is adapted to detect the level of liquid (e.g., blood and/or saline) within the drip chamber  110 . The drug delivery line  140  of the drug delivery line set  106  is connected to the blood line set  112  at a location between the dialyzer  134  and the drip chamber  110  via a luer lock connector  142  disposed on the drug delivery line  140 . Specifically, the luer lock connector  142  is connected to a mating luer locking fitting on a level adjust line  144  that is connected to the top of the drip chamber  110 . A clamp  147  is attached to the level adjust line  144  and is used to permit or block fluid from passing between the drug delivery line set  106  and the blood line set  112 . 
         [0053]    The drug delivery line set  106  includes the drug delivery line  140 , which is connected to the drug delivery module  104  in a manner so as to operatively engage the drug pump  150  of the drug delivery module  104 . When the drug pump  150  is being operated, a vacuum pressure (e.g., up to about −12 psi) is applied to the drug vial  108  that is connected to the drug delivery line  140 . In certain cases, the initial pressure in the drug vial  108  can vary slightly from above to below ambient pressure due to variations in conditions during manufacturing. The initial air volume within the drug vial  108  is generally 2 ml of air or less (e.g., from about 0.40 ml to 1.75 ml of air) due to drug vial arrangements (e.g., total interior volume, ambient pressure during vial filling, and stopper volume), and when all of the drug has been delivered, the ending pressure within the vial is −15 psi or less (e.g., −7 to −15 psi). As the quantity of drug in the drug vial decreases, a vacuum (or negative pressure) within the drug vial increases because the drug vial  108  is not vented. In other words, the pressure within the drug vial  108  progresses from 14.7 psi toward −15 psi (e.g., −7, −7.22, −8, −13, −13.6 psi) as the drug is being delivered. In certain cases, the vacuum generated in the drug delivery line  140  exceeds the vacuum within the drug vial  108 . As a result, the drug is drawn from the drug vial  108  through the drug delivery line  140 . However, when the pump  150  is unable to generate a vacuum in the drug delivery line  140  that exceeds the vacuum in the drug vial, the pump  150  can no longer draw drug from the drug vial  108  into the drug delivery line  140 . Thus, any remaining drug within the drug vial  108  is not delivered to the patient. The remaining drug can result in under-delivery of a drug to the patient and/or limit the amount of available drug per drug vial. 
         [0054]    As shown in  FIG. 3 , the drug delivery line set  106  includes the vial adapter  136  to which the drug delivery line  140  is attached. The drug delivery line set  106  also includes a priming cap  116  that is removably attached to the drug delivery line  140 . The drug delivery line  140  and the priming cap  116  include sterile air. The priming cap  116  includes a bistable diaphragm  156 , which defines a top boundary of an internal chamber  151 . The air volume can be selected such that, upon activation of the priming cap  116 , the bistable diaphragm  156  displaces a sufficient air volume into a drug vial (e.g., the drug vial  108 ) to enable a pump (e.g., the drug pump  150 ) to deliver the desired dosage or substantially all of the drug (e.g., 100%, at least 95%, at least 90%, or at least 80%) within the drug vial based on the capabilities of the pump. For example, the internal chamber  151  can be sized and shaped to store an air volume of about 3 ml or less (e.g., 0.5 ml or less, 1 ml or less, 1.5 ml or less, or 2 ml or less), which can be delivered into a drug vial (e.g., the drug vial  108 ) through the drug delivery line  140  when the priming cap  116  is activated. 
         [0055]    In addition to the priming cap  116 , the drug delivery line set  106  can include a spike cover  154  is removably secured to the vial adapter  136  by an interference fit. The spike cover  154  can be made of a moldable material, e.g. polyethylene. The spike cover  154  is removed from the vial adapter  136  prior to use to allow a drug vial (e.g., the drug vial  108 ) to be inserted into the vial adapter  136 . 
         [0056]      FIGS. 4A and 4B  illustrate the drug delivery line set  106  with the drug vial  108  inserted into the vial adapter  136 . The bistable diaphragm  156  is movable between a first position in which the bistable diaphragm  156  assumes a convex shape (as shown in  FIG. 4A ) and a second position in which the bistable diaphragm assumes a concave shape (as shown in  FIG. 4B ). For example, the bistable diaphragm  156  is convex prior to being depressed in the direction shown by an arrow  141  and is concave after the priming cap  116  is depressed. Activation of the priming cap  116  is achieved by depressing the convex surface to create a concave surface. 
         [0057]    The priming cap  116  can be made from a plastic material (e.g. high density Polyethylene (HDPE), polyethylene, polyvinylchloride, polyamide, or a blend of moldable plastics). The bistable diaphragm  156  can be economically produced using an injection molding technique, for example. The priming cap  116  removably attaches to the drug line  140  using a luer connection to form an air-tight seal with the fluid line  140 . Other air-tight connection mechanisms may also be used (an interference fit). 
         [0058]    The drug delivery line set  106  also includes a one-way valve  145  (e.g., a check valve) between the luer lock connector  142  of the drug delivery line set  106  and the drug vial  108 . The one-way valve  145  permits delivery of air from the internal chamber  151  to the drug vial  108 , but prevents air from re-entering the priming cap  116  when the bistable diaphragm  156  is deformed and/or released. The one-way valve  145  may be a duckbill valve, an umbrella valve, a ball-check valve, diaphragm check valve, swing check valve, stop-check valve, lift-check valve or a combination thereof. 
         [0059]    As drug is delivered from the drug vial  108 , any remaining air within the drug vial  108  expands and a vacuum pressure within the drug vial  108  increases. The final pressure within the drug vial can be determined with the following equations: 
         [0000]      P atm (V initial air )=P vial (V min. air )  Equation 1 Minimum Final Vial Pressure
 
         [0000]      P atm (V initial air )=P vial (V max. air )  Equation 2 Maximum Final Vial Pressure
 
         [0000]    where 
         [0060]    P atm  is atmospheric pressure. 
         [0061]    V initial air  is the initial volume of air inside the vial; 
         [0062]    P vial  is the final pressure within the vial; and 
         [0063]    V max  is maximum volume of air inside the vial. 
         [0000]    By subtracting the pressure within the drug delivery line  140  (e.g., ambient pressure or 14.7 psi) from the calculated final vial pressure, the pumping capability necessary to evacuate all drug can be determined. The initial volume of air inside the vial can be adjusted such that pump (e.g., the drug pump  150 ) can generate a vacuum (based on the capabilities of the pump) in the drug line that exceeds final vacuum within the drug vial in view of the maximum and minimum conditions given arrangement of a drug vial (e.g., the total vial volume, the air volume, the drug volume, and the stopper volume). This adjustment helps to ensure that the medical systems described herein remain compatible with a variety of drug vial designs and/or manufacturing deviations without replacing or upgrading system components (e.g., pumps). 
         [0064]      FIG. 5  shows the drug delivery line set  106  connected to the drug delivery module  104  prior to connecting the drug delivery line  140  to the blood line set  112 . As shown, the end of the drug delivery line  140  is connected to a storage clip  148  of the drug delivery module  104 . The drug delivery line  140  passes through a peristaltic drug pump  150 . Prior to use, a user will prime the drug vial  108  with air by depressing the priming cap  116 , which will be explained in further detail later. A user then would unclip the drug delivery line  140  from the storage clip  148  and connect it to the blood line set  112  in the manner shown in  FIGS. 1 and 2 . 
         [0065]    Still referring to  FIG. 5 , the drug delivery module  104  includes a fluid flow detector  152 . The fluid flow detector  152  is capable of detecting air bubbles within the drug delivery line  140 . As a result, the fluid flow detector  152  can determine whether the drug vial  108  is empty. In some implementations, the fluid flow detector  152  is an optical detector. The OPB  350  level detector made by Optek® can, for example, be used. Other types of optical detectors can alternatively or additionally be used. Similarly, other types of sensors, such as sensors utilizing ultrasound technology can be used as the fluid flow detector. Examples of such sensors include the AD8/AD9 Integral Ultrasonic Air-In-Line, Air Bubble Detector and the BD8/BD9 Integral Ultrasonic Air Bubble, Air-In-Line &amp; Liquid Level Detection Sensors (manufactured by Introtek® International (Edgewood, N.Y.)). In some implementations, the fluid flow detector  152  includes a sensor that, in addition to sensing the presence of an air bubble within its associated drug delivery line  140 , can sense the presence of the drug delivery line  140  itself. 
         [0066]    Still referring to  FIG. 5 , the drug delivery line  140  passes through (e.g., is threaded through) the peristaltic drug pump  150 . The peristaltic drug pump  150  works by compressing the drug delivery line  140  and moving a “pillow” of fluid that is pinched between two points of the drug delivery line  140  by the pump rollers. Each “pillow” of fluid is of a volume determined by the roller spacing and the inside diameter of the drug delivery line  140 . When the peristaltic drug pump  150  operates at a given speed, a series of these “pillow” shaped volumes of fluid are delivered to the drip chamber  110 . The rate of fluid delivery can be changed by altering the speed of the peristaltic drug pump  150 . The pump speed can be controlled, for example, by adjusting the voltage delivered to the peristaltic drug pump  150 . The voltage delivered to the motor of the peristaltic drug pump  150  can, for example, be adjusted by the control unit (e.g., software of the control unit) until the correct speed (e.g., the speed that corresponds to the desired flow rate) is measured by an encoder of the peristaltic drug pump  150 . 
         [0067]    During use, the drug delivery line set  106  is fluidly connected to the blood line set  112  of the hemodialysis system  100 , as shown in  FIGS. 1 and 2 . Drugs are delivered to the drip chamber  110  using the drug delivery module  104 . The drugs mix with the patient&#39;s blood within the drip chamber  110  and are then delivered to the patient along with the patient&#39;s filtered blood. 
         [0068]      FIG. 6  illustrates the vial adapter assembly with the spike cover  154  removed from the vial adapter  136 . The vial adapter  136  includes circumferentially spaced side wall segments  157  that extend upwardly from a base  155  to form a receiving cavity  159  sized and shaped to receive a drug vial. A spike  164  extends from a central region of the base  155  and is sized and shaped to pierce a seal of the drug vial when the drug vial is inserted into the receiving cavity  159 . The spike  164  has a central passage in fluid communication with a cavity  163  of the spike cover  154  when the spike cover  154  is positioned over the spike  164 . 
         [0069]    As shown in  FIG. 6 , the circumferential side wall segments  157  of the vial adapter  136  extend to a slightly greater height than the spike  164  of the vial adapter  136 . Adjacent side wall segments  157  are spaced apart by longitudinal/vertical slots  153 . The side wall segments  157  together with the base  155  form the receiving cavity  159  that is configured to receive a portion of a drug vial (e.g., a collar of a drug vial cap assembly). In some implementations, the receiving cavity  159  is configured to receive a collar having a diameter that is about 0.75 inches to about 1 inch (e.g., about 0.875 inches.) The side wall segments  157  are configured to deflect away from the longitudinal axis of the vial adapter  136  when a radially outward force is applied (e.g., as a result of the drug vial being inserted into the receiving cavity  159 ) and rebound towards the longitudinal axis when the force is released. 
         [0070]    Still referring to  FIG. 6 , protrusions  161  on side wall segments  157  of the vial adapter  136  help secure a vial within the receiving cavity  159  of the vial adapter  136 . The extension of the side wall segments  157  to a slightly greater height that the spike  164  of the vial adapter  136  also help to ensure that the spike  164  is not inadvertently contacted (e.g., by the user) prior to loading of the drug vial  108  onto the spike  164 . This can, for example, help to prevent the spike  164  from becoming contaminated before it is inserted into the drug vial. 
         [0071]    In some implementations, the spike  164  is formed of one or more medical grade plastics, such as PVC or acrylonitrile butadiene styrene (ABS). However, other medical grade plastics can be used to form the spike  164 . Similarly, certain metals, such as stainless steel, could be used to form the spike  164 . 
         [0072]    Another feature of the vial adapter assembly that prevents inadvertent contact and contamination is the spike cover  154 . The spike cover  154  is placed into the receiving cavity  159  of the vial adapter  136  to cover the spike  164 . The spike cover  154  can help prevent objects from contacting and contaminating the spike  164  prior to use and can also prevent users from inadvertently sticking themselves with the spike  164 . The spike cover  154  is configured to be received in the receiving cavity  159  and temporarily retained by the side wall segments  157 . For example, the spike cover  154  can be retained via a loose interference fit. The side wall segments  157  provide a resisting force of about 0.75 lbf to about 2 lbf to retain the spike cover  154  when it is retained by the vial adapter  136 . 
         [0073]    Prior to hemodialysis, the user connects the drug delivery line set  106 , which includes the vial adapter  136 , the spike cover  154 , and the drug delivery line  140 , to the drug delivery module  104  of the hemodialysis machine  102 . The drug delivery line set  106  is typically provided to the user in a sterile bag with the priming cap  116  connected to the end of the drug delivery line  140  opposite the vial adapter  136 . To connect the drug delivery line set  106  to the drug delivery module  104 , the user first opens the sterile bag and removes the drug delivery line set  106 . 
         [0074]    Referring to  FIG. 7 , the user then opens a door  158  of the fluid flow detector  152 , places the vial adapter assembly (e.g., the vial adapter  136  and spike cover  154 ) into a vial holder  160 , and threads the drug delivery line  140  through a bubble detector  162  of the fluid flow detector  152 . The user also opens a door  166  of the peristaltic drug pump  150  and threads the drug delivery line  140  through the peristaltic drug pump  150 . The door  166  typically remains open so that the drug delivery line  140  is not crimped between the door  166  and the rollers of the peristaltic drug pump  150 . This permits both fluid and air to flow freely through the drug delivery line  140 . 
         [0075]    Referring to  FIG. 8 , the drug vial  108  is placed on the vial adapter  136  so that a spike  164  pierces a seal of the drug vial  108  and places the vial in fluid connection with the drug delivery line set  106  (e.g., as shown in  FIGS. 1 and 2 ). When placed on the vial adapter  136 , the seal and the spike  164  form a fluid- and air-tight seal. A user then depresses and/or deforms the priming cap  116  (as shown in  FIG. 4B ) to deliver air into the drug vial  108 . 
         [0076]    Referring to  FIG. 9 , the user then closes the door  166  of the peristaltic drug pump  150  and the door  158  of the fluid flow detector  152 , engaging the peristaltic drug pump  150  and the fluid flow detector  152  with the drug delivery line  140 . As discussed above, the drug delivery line  140  is crimped within the door  166 . This arrangement helps to retain the modified drug vial pressure and/or the additional air when, for example, a priming cap is removed and/or the drug line is fluidly connected to another line because portions of the drug line  140  downstream from the door  166  may equalize with another pressure, e.g., with the pressure within the blood line set. 
         [0077]    Referring to  FIG. 10 , the drug delivery line  140  is then connected to the drip chamber  110  using an aseptic technique. As discussed above, this typically involves removing the priming cap  116  and connecting the luer lock connector  142  on the end of the drug delivery line  140  to a mating luer lock fitting on the level adjust line  144  extending from the drip chamber  110 . In addition, a priming fluid bag  168  is connected to the blood line set  112  via a priming fluid line  169 . The priming fluid bag  168  is connected to the priming fluid line  169  by a luer lock connection. The priming fluid line  169  also includes clamps  171  and  172  that are used to regulate the fluid flow from the priming fluid bag  168  to the blood line set  112 . The patient lines  126  and  128  are connected to each other via a luer connector  173  at this point to allow priming fluid to circulate through the blood circuit. 
         [0078]    Still referring to  FIG. 10 , after the drug delivery line set  106  has been connected to the drip chamber  110 , which is attached to the level detector module  124 , the peristaltic drug pump  150  is then operated to deliver drug to the drip chamber  110  of the blood line set  112 . For example, the system can undergo a priming process in which the drug pump  150  causes a portion of the drug to be drawn from the drug vial  108  until the drug is detected by the bubble detector  162 . The blood pump  132  is also operated to cycle priming fluid through the blood line set  112  and through the dialyzer  134 . Air within the blood circuit and drug delivery line can collect in the drip chamber  110  and then be removed from the system prior to treatment. 
         [0079]    After priming is complete, the priming fluid line  169  is disconnected from the blood circuit or clamped, and the patient lines  126  and  128  are disconnected from each other and connected to the patient to allow the patient&#39;s blood to circulate through the blood circuit. During treatment, the peristaltic blood pump  132  is operated to pull blood from the patient via the arterial patient line  126 , run the blood through the blood circuit, and then return the blood to the patient via the venous patient line  128 . The drug pump  150  is operated to deliver drug from the drug vial  108  to the drip chamber  110  through the drug delivery line  140 . The drug can mix with the blood in the drip chamber  110  before flowing to the patient. 
         [0080]    As discussed above, the drip chamber  110  of the hemodialysis system  100  functions as an air trap. Thus, any gases (e.g., air) introduced into the system are able to escape from the drug and blood within the drip chamber  110  before the mixture of blood and drug is delivered to the patient. In addition to removing air from the system, the drip chamber  110  provides other benefits. For example, the drip chamber  110  provides visual confirmation of drug delivery and allows the delivered drug to mix with the patient&#39;s blood prior to reaching the patient. In addition, the drip chamber  110  allows for simple luer connection to the drug delivery line set  106 . As a result, the patient need not be stuck with an additional needle in order to receive the drug from the drug vial  108 . 
         [0081]    While certain embodiments have been described, other embodiments are possible. 
         [0082]    While the priming cap  116  has generally been shown and described as monolithic, the priming cap  116  can be a composite structure where the bistable diaphragm  156  is an attachable component that could be a different material from the main body of the priming cap. The bistable diaphragm  156  can be attached to the main body of the priming cap with any attachment known in the art, such as adhesives, fasteners, or welding. 
         [0083]    Referring to  FIGS. 11A and 11B , while the priming cap  116  has been generally shown as having an asymmetric body partially defined by the bistable diaphragm  156 , the priming cap  116  can alternatively or additionally have a uniform compressible body such that any portion of the priming cap can be compressed to introduce air to the drug vial  108 . For example, the priming cap can include a compressible body portion  177  (e.g., a bulbous portion) surrounding an internal gas chamber  178  in fluid communication (e.g., via an internal passage) with an integral neck portion  175  extending from the compressible body portion  177 . The compressible body portion  177  can alternatively or additionally have a uniform shape. For example, the compressible body portion  177  can be arranged as an elliptical cylinder with at least one spherical end (as shown in  FIG. 11A ) or as a cylinder with at least one spherical end (as shown in  FIG. 11B ). The integral neck portion  175  can include a fluid-tight (e.g., air-tight) connection (as described with above) to removably connect the priming cap  116  to the fluid line. Compressing the body portion  177  can deform a portion of the deformable wall structure  180 , thereby reducing the volume of the internal gas chamber  178  and expelling at least a portion of gas (e.g., air and/or sterile air) from the interior gas chamber  1758 . The deformable wall structure  180  defines at least a top surface and a bottom surface of the internal gas chamber  178 . This arrangement provides multiple surfaces for a user to deform and/or compress to deliver gas to the drug vial  108  via the drug line  140 . 
         [0084]    While the diaphragm has been described as being bistable, in some embodiments, it can have a single stable state. The user continuously depresses the diaphragm in order to maintain the additional air displaced into the drug vial. The user can control the amount of air delivered based on the amount of pressure the user places on the diaphragm. The user can connect the drug delivery line set to the drip chamber while depressing the diaphragm. 
         [0085]    While the priming cap  116  has generally been shown to include a one way-valve, in some embodiments, the priming cap can additionally or alternatively be arranged to occlude the drug delivery line  140  via depression of the bistable diaphragm  156 , thereby preventing air from re-entering the priming cap  116 . Upon depression and/or deformation, the bistable diaphragm  156  can contact an opposing wall surface to form a fluid-tight seal until the cap is removed. 
         [0086]    While a luer lock connection has been described as being used to fluidly connect the drug delivery line set with the priming cap  116  and the drip chamber, any of various other types of fluid connections can be implemented, such as an interference fit, tab connection, or temporary adhesive. 
         [0087]    While during priming the drug vial the drug delivery line is generally shown as threaded through the peristaltic drug pump, the drug delivery line may remain outside of the peristaltic pump before the priming cap  116  is removed. For example, a user can deform or depress the priming cap  116  before threading the drug delivery line through the peristaltic drug pump (e.g., over the pump rollers). 
         [0088]    While the hemodialysis machine has generally been shown to include modules used to perform hemodialysis, including the drug delivery module, the blood pump module, and the level detector module, other modules may also be included. For example, a heparin pump module may also be included. The heparin pump module can include a heparin pump that receives a syringe connected to a drug delivery line that is connected to the blood line at a location between the blood pump. The syringe pump can be operated to move a plunger of the syringe and thus eject liquid from the syringe through the drug delivery line. The heparin pump module can thus be used to inject heparin from the syringe into the blood circuit via the drug delivery line during a hemodialysis treatment. 
         [0089]    While the drug delivery devices have been described as being used with hemodialysis systems, the devices, assemblies, and methods described herein can be used with various other types of drug delivery processes and systems. For example, in some implementations, the drug vial spiking devices are used for delivering drugs during peritoneal dialysis treatments, blood perfusion treatments, intravenous infusion treatments, or other medical fluid handling treatments, such as delivering drugs intravenously. 
         [0090]    A number of implementations have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the description. Accordingly, other implementations are within the scope of the following claims.