Abstract:
A syringe is partitioned into at least proximal and distal chambers to provide a multi-chamber, sequentially dispensing syringe apparatus. The syringe includes a gas separator that prevents gas from exiting a chamber with delivered fluid.

Description:
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS 
       [0001]    This patent application is a continuation of U.S. patent application Ser. No. 11/446,779, entitled “Safety Dispensing System for Hazardous Substances,” filed on 5 Jun. 2006, published on 5 Oct. 2006 as U.S. Patent Application Publication No. 2006/0224105, which is a continuation-in-part of U.S. patent application Ser. No. 11/359,304, entitled “Mixing Syringe With and Without Flush,” filed on 21 Feb. 2006, issued 5 Sep. 2006 as U.S. Pat. No. 7,101,354, which is a continuation-in-part of U.S. patent application Ser. No. 11/284,504, entitled “Multi-Chamber, Sequential Dose Dispensing Syringe,” filed on 22 Nov. 2005, issued on 23 May 2006 as U.S. Pat. No. 7,048,720, which is a continuation-in-part of U.S. patent application Ser. No. 10/838,101, entitled “Multi-Chamber Sequential Dose Dispensing Syringe,” filed on 3 May 2004, issued on 14 Feb. 2006 as U.S. Pat. No. 6,997,910 (referred to herein as “Howlett”), each of which is incorporated by reference herein in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    This invention relates to multi-chamber syringes and, in particular, to syringes which dispense fluid from each chamber sequentially. 
       BACKGROUND 
       [0003]    During the last forty years, parenteral drug delivery has become increasingly common and sophisticated. It is currently estimated that nearly 90% of hospital patients receive IV medications, often through a variety of apparatus, including expensive electronic IV pumps and multi-channel infusion systems. Home care patients may receive antibiotics through an elastomeric “ball” pump. Syringe pumps are common in many hospital and alternate site settings and are often used as a low cost alternative to more expensive IV pumps. 
         [0004]    Virtually all IV medications, administered through a catheter or IV tubing, should be flushed into the vascular system with saline or a similar physiologically compatible flushing fluid. Such flushing assures that a patient receives a full dose of medication, some of which otherwise might remain in the associated IV tubing or catheter. Flushing also assures that a subsequently infused incompatible medication does not come in contact with a previous one. It is well known in the infusion art that flush solutions are also used to keep an infusion line patent or open. 
         [0005]    With rising healthcare costs, and an ever increasing shortage of nurses and pharmacists, there is a strong motivation to streamline basic procedures, such as IV catheter flushing to save clinician time. Noting that flushing usually necessitates use of a second flushing syringe (which is often currently factory pre-filled), the flushing syringe represents added cost, not only in clinician time, but in terms of required additional syringes. Use of multiple syringes also increases risk of medication error (incorrect selection of flushing liquid) and introduction of microorganisms (a function of number of IV line or catheter accesses). 
         [0006]    As an example, it is currently estimated that there are over 500 million antibiotic and chemotherapy medications administered annually in the United States. Each of these administrations are taught to require a follow-on flush, currently necessitating use of a second syringe in most cases. Combining antibiotic or chemotherapy and flush medications in one multi-chamber, sequential dose syringe promises to save over 500 million syringes, yearly in the United States alone, plus that additional time required for two syringe delivery. 
         [0007]    Multi-chamber syringes in various forms are well known. Commonly, multi-chamber syringes are offered for use as mixing syringes and for sequential delivery of disparate fluids, maintaining the fluids as disparate entities until delivered. Mixing syringes most often provide features for mixing contents of the chambers and for delivering the mixed fluids simultaneously. Though this invention may utilize a mixing syringe within one or more chambers, the invention, itself, is independent of methods of mixing which may be utilized in mixing syringes. 
         [0008]    Generally, within each serial delivery syringe, chambers are separated by an intermediate sliding stopper which receives motive force communicated through an intermediate fluid from a primary stopper which is part of a plunger assembly against which an external force is applied. For disparate fluids to be dispensed sequentially or serially, each intermediate stopper should provide a fluid-tight seal until all fluid from a distal chamber is evacuated from the syringe. Once the distal chamber of the syringe is so purged, that intermediate stopper must be breached or bypassed to permit dispensing of the contents of a proximal or intermediate chamber. 
         [0009]    An example of a multi-chamber syringe is provided in U.S. Pat. No. 4,929,230 titled “Syringe Construction” and issued May 29, 1990 to Frederick W. Pfleger (Pfleger). Pfleger teaches a distortable piston which is used as the intermediate stopper. The piston of Pfleger collapses upon contact with a distal end of a syringe to provide a fluid pathway to dispense contents from the intermediate chamber. 
         [0010]    While a syringe made, as an example, according to Pfleger appears to provide a solution for sequentially dispensing disparate fluids, there are a series of concerns which would necessarily be associated with using such a syringe to dispense sequential doses of medications. A first concern arises, for example, when it is recognized that such a syringe may be used to dispense an accurately measured dose of a very expensive medication into an IV apparatus from a distal chamber of a multi-chamber syringe. Then, immediately following dispensing the first medication, a volume of a following solution is dispensed through the IV line to fully flush the first solution. 
         [0011]    Clearly, a deformable piston, having a hollow portion, such as the stopper of Pfleger would not have zero dead space. Also, it is well known that filling procedures for contents of the proximal chamber may permit a quantity of air (or other gas) to be trapped therein. It may be noted that even if such gas is not trapped during filling, free gas may be found in the proximal chamber simply as a result of out-gassing. Pfleger does not teach a way of purging the proximal chamber of gas or of containing any gas in the proximal chamber while only dispensing liquid therefrom, making such a system unacceptable for use in directly administering intravenous liquid medications to a patient. While other art may provide more effective ways to deal with the dead space issue, there is no known art which teaches a way of delivering only liquid from the proximal or intermediate chambers. That such may be a problem is recognized by U.S. Pat. No. 5,236,420 titled BYPASS, PRESSURIZED PISTON FOR CHAMBERS issued Aug. 17, 1993, also to Frederick W. Pfleger, discloses a valved plunger which may be used to evacuate gas from a proximal syringe chamber. 
         [0012]    Other art, such as U.S. Pat. No. 6,027,481 issued Feb. 22, 2000 to Laurent Barrelle, et al. (Barrelle) and U.S. Pat. No. 5,851,200 issued Dec. 22, 1998 to Tetsure Higashikawa, et al. (Hagashikawa) disclose multi-chamber syringes with sliding valves. However, in each case, Barrelle and Higashikawa teach special structure requirements imposed upon a syringe barrel (a channel in the case of Barrelle and a bulge in the case of Higashikawa) which is used to provide a fluid pathway about a stopper. 
         [0013]    Another U.S. Pat. No. 6,723,074 B1, titled Sequential Delivery Syringe and issued Apr. 20, 2004 to Thor R. Halseth (Halseth) teaches a sequential delivery syringe which utilizes a modification to a discharge opening of a syringe for providing access to a rear chamber of a two chamber syringe. The modification comprises disposing a piercing member at the discharge opening. The piercing member punctures a “mid-piston” and a collapsible bag disposed in a rear chamber to provide access to fluid in the bag. Access occurs when the mid-piston is displaced by action of a plunger and stopper piston to cause the mid-piston and bag to contact the piercing member. 
         [0014]    Definition of Terms 
         [0015]    Following is a brief list of clarifying definitions for the terms used herein: 
         [0016]    Assembly n: a device which is made from at least two interconnected parts 
         [0017]    Barrel n: a cylindrical elongated portion of a syringe which is conventionally open on one end to receive a plunger and stem used for displacing fluid within the barrel and partially closed at an opposite end except for an orifice through which fluid is ejected or aspirated 
         [0018]    Bi-stable adj: a descriptor for a device having two stable states 
         [0019]    Clinch n: a structure or device which acts upon a part to clamp it closed while in contact therewith 
         [0020]    Conventional adj: a sanctioned by general custom; i.e. commonplace, ordinary 
         [0021]    Chamber n: a volumetric portion of a divided barrel 
         [0022]    Disparate n: when used in conjunction with a liquid volume, a volume of liquid which is distinctly separate from another liquid volume 
         [0023]    Differential pressure (ΔP) n: a pressure gradient resulting from unequal pressures exerted upon opposing sides of a structure; generally as used herein, ΔP=P p −P d    
         [0024]    Distal adj: a term which depicts placement away from a reference point (e.g. away from a user of a syringe) 
         [0025]    Dome n: an arcuately shaped surface (e.g. a hemisphere) 
         [0026]    Downstream adj: a direction which is consistent with flow out of a syringe or away from a user 
         [0027]    Fluid n: a substance (e.g. a liquid or gas) which tends to take the shape of a container 
         [0028]    Front adj/n: distally disposed or a distally disposed site (e.g. a front of a syringe comprises the barrel orifice) 
         [0029]    Gas n: a fluid which is neither solid nor liquid 
         [0030]    Gas separator n: a liquid filter which inhibits gas flowing there through 
         [0031]    Liquid n: a fluid which is neither solid nor gaseous, free flowing like water 
         [0032]    Non-planar adj: not planar in a resting or stable state 
         [0033]    Medial adj: occurring away from an outer edge; disposed near the center of (e.g. disposed away from an edge or periphery and in the vicinity of a center of gravity or axis of symmetry) 
         [0034]    P d  n: pressure in a distal chamber 
         [0035]    Plunger n: a portion of a syringe piston apparatus usually affixed to a syringe stem which is used to displace fluid within a syringe barrel 
         [0036]    Prime v: to fill liquid into a cavity generally by removing air therefrom (e.g. priming a gas separator) 
         [0037]    P p  n: pressure in a proximal chamber 
         [0038]    Proximal adj: opposite of distal (e.g. a term which depicts placement nearer than a reference point) 
         [0039]    Rear adj: opposite from front (i.e. generally associated with a part of a syringe barrel which is proximal to a syringe user) 
         [0040]    Reflux n: a type of undesired retrograde (upstream) flow of liquid (e.g. blood) into a catheter or the like from a vessel in which the catheter or the like resides 
         [0041]    Separator n: a liquid filter which impedes passage of air as liquid flows through the separator 
         [0042]    Stiction n: a special case of friction; stiction being the force required to initiate motion to a resting body, esp. when stiction is greater than moving friction 
         [0043]    Stem n: an elongated part which fits within a syringe barrel and is affixed to a plunger for the purpose of displacing fluid within the barrel 
         [0044]    Stop n: a obstruction which is differentiated from friction or stiction which halts displacement of a stopper or plunger 
         [0045]    Stopper n: a plunger associated with a stopper assembly, in the instant invention, the stopper contains a self-actuating bi-stable valve 
         [0046]    Syringe n: a device used for injecting or withdrawing fluids 
         [0047]    Upstream adj: a direction which is against the direction of flow from a syringe (opposite of downstream) 
       SUMMARY 
       [0048]    In brief summary, the currently preferred embodiment of this novel invention alleviates all known problems related to providing an effective multi-chamber, sequential dose dispensing syringe. Inherently, the invention involves a stopper assembly which is disposed to operate within a conventional, substantially constant diameter syringe barrel to separate a distal chamber from a proximal chamber. Before dispensing, the distal chamber generally contains a first volume of liquid. The proximal chamber contains a disparate second volume of fluid. A closed valve in the stopper assembly keeps the contents of each chamber separate from the other. 
         [0049]    In this currently preferred embodiment, the stopper assembly comprises two elements, a valved stopper and a stopper stabilizer and gas separator (referenced hereafter as a “separator”). The valved stopper contains a valve mechanism which is only actuated to open after the stopper is displaced to collide with an associated distal end of the syringe (or another stop within the syringe) in which the stopper assembly is disposed. This embodiment, though novel on its own, is related to the invention disclosed in Howlett, the U.S. patent application from which this application claims priority. 
         [0050]    In all embodiments of Howlett and this instant invention, action upon a plunger associated with the syringe communicates through the second volume of fluid to displace a stopper assembly to the syringe end, open the valve thereby dispensing liquid from the distal chamber. Upon complete evacuation of the liquid from the distal chamber and by collision of the stopper assembly with the distal internal end surface of the syringe (or another stop), a positive differential pressure across the stopper assembly resulting from force against the syringe stem causes the valve to be opened. Thus, continuous action upon the stem of the syringe permits sequential and selective dispensing of liquid contents from the proximal chamber following dispensing of fluid from the distal chamber. 
         [0051]    In a preferred embodiment of this invention, the valve assembly comprises a bi-stable valve structure, the valve itself being characterized as a slit valve. It should be noted that a stopper assembly according to this instant invention operates in an unmodified standard or conventional syringe barrel, requiring no unconventional barrel features. Examples of some previously cited special features which may be placed in modified syringe barrels are found in Barelle and Hagashikawa. Note that bi-stable action of the valve provides for syringe operation only after valve opening which mimics in all ways operation of a conventional syringe. Also, with the valve remaining in an open state after pressure is removed from the proximal chamber, any residual pressure associated with stored energy within the proximal chamber acts against reflexive flow to thereby oppose reflux in an attached catheter or other dispensing tube. 
         [0052]    Selective opening of the valve is based upon a common geometry of most, currently commercially available conventional syringe barrels. All such syringe barrels have a substantially constant diameter hollow barrel abruptly closed at a distally disposed inner surface. Distally, the inner surface commonly comprises a centrally disposed orifice through which fluid is dispensed from the barrel. Generally, a plunger, with an associated stopper affixed thereto, is provided for forced displacement of fluid through the barrel and orifice. 
         [0053]    To prevent premature mixing of the disparate solutions in syringe chambers, the stopper assembly valve should open only upon being displaced to its most distal site in contact with the distal end of the syringe barrel (a stop). For this reason, the stopper assembly comprises a structure which is affected by collision between a surface at that distal site (the stop) and, then, reacts to open the valve when additional pressure is forced upon the valve. In addition, to assure that the valve remains absolutely closed until fluid is dispensed from the distal chamber, the separator is preferably disposed and structured to act as a clinch, applying a closing, supporting force upon the valve until the valve is displaced from the clinch by a downstream-directed positive differential force across the valve. 
         [0054]    To assure effective clinching support by the separator prior to opening the valve, the separator should be securely connected to the valved stopper and be displaced as the valved stopper is displaced. As is well understood in fluid mechanics, displacement of a substantially incompressible fluid in a proximal chamber of a syringe barrel interposed between a combination of a proximally disposed syringe stem and associated plunger and a distally disposed valve assembly, results in like displacement of the valve assembly as the stem and associated plunger are displaced. The valved stopper and separator of the instant invention, therefore, comprise an interlocking interface which causes the separator to be securely affixed to the valved stopper and to be jointly displaced as the stem stopper is displaced. 
         [0055]    An important feature of a multi-chamber syringe is a provision for only dispensing flow from any proximally disposed chamber (relative an initial distal chamber) to guard against reflux (retrograde flow) into a catheter or tube upon completion of a given dispensing cycle or operation. For this reason, a valve assembly should operate to impede retraction of fluid at the end of such dispensing or at completion of a dispensing operation. When no interlock is available from an external associated part, such as from the separator, a valve disposed within the valved stopper should be self actuating and, once open should either close without drawing fluid back into the syringe or remain open to assure that no reflux occurs. Therefore, it is preferred that a valve disposed in the stopper assembly be bi-stable. (i.e. the valve is stable in the closed state until forced open and be disposed to remain in a stable open state, once opened.) 
         [0056]    In a preferred construction, such a valve is non-planar (e.g. the valve structure may be dome shaped). In the case of a dome-shaped valve, care should be taken to assure that displacement of the valve upon switching does not collide with the front inner surface of the associated syringe to thereby make switching and opening of the valve difficult. 
         [0057]    Non-planar or dome valves are well known, especially for self closing food containers. As an example, U.S. Pat. No. 5,213,236 issued May 25, 1993 to Paul E. Brown, et al. (Brown), discloses a slit valve having a rotating hinge. However, Brown discloses a slit valve which is opened by pressure applied to an associated container and which is self closing when pressure is taken from the container. By repetition, it is emphasized that, for two very important reasons, a valve according to the instant invention should not so close after being opened. First, such closure would most likely cause fluid to be withdrawn from an output flow path and, second, force of closing would act against force being used to drive liquid from the proximal chamber, making purging of the proximal chamber more difficult than if the valve were bi-stable and remains in an open state. 
         [0058]    Of course, the slit valve should only open when the valve assembly collides with the distal inner surface of the associated syringe or stop. In all other cases, until so opened, the valve should remain securely closed. As a syringe operation may require bi-directional displacement of a syringe stem and resulting bi-directional displacement of the valve assembly, it is important to construct the valved stopper and separator to properly provide closure support, if needed, by the slit valve in all such modes of displacement. For this reason, the separator, which is securely affixed to the valved stopper and thereat disposed about the valve slit as a clinch, preferably comprises a set of ribs which cooperate to provide clinching support for the valve about the slit. Thus restrained, the slit valve does not open inappropriately, especially when the syringe stem is proximally displaced. 
         [0059]    As noted in the parent patent application(s), when pre-filled doses are stored in the proximal chamber for ultimate use, it is not uncommon for gas (most commonly air) to collect in a non-insignificant bubble size there inside. It is not good medical practice to dispense that gas into a patient line (e.g. an IV line). To preclude such an occurrence, the valve assembly comprises a liquid filter which is interposed across fluid flow through the valve to act as a gas separator. The gas separator is formed in a centrally disposed portion of a a separator body which may be made as a hollow frustoconical shape, being open at the bottom. A series of small, closely spaced holes are dispersed about the conical sides of the separator body. The top (proximal face) of the frustoconical or thimble shaped body is closed except for at least one hole which provides a sufficiently large exit to permit purging of gas from the separator and delivery of at least part of the liquid from the proximal chamber therethrough. The bottom of the separator is open and disposed distally toward the valved stopper to contact the inner surface of the stopper about the slit. An outwardly projecting rim about the bottom of the separator provides an interlocking surface for a complimentary groove molded into the valved stopper about the slit. 
         [0060]    Also, stability of a freely displaced valve assembly within the barrel of a syringe should be considered. The body of the separator is provided with sufficient radially extending appendages to inhibit valved stopper canting. 
         [0061]    The valve assembly may be made from only two parts. The valved stopper may be molded from flexible synthetic resinous material, consistent with material used in plunger stoppers. The separator may be injection molded from semi-rigid synthetic resinous material which is non-interactive with solutions stored in the proximal chamber. Such a material may be polypropylene and may be the same material used in an associated syringe barrel. 
         [0062]    A critical factor in a valve assembly used in multi-chamber syringes is assembly cost. Such assembly should be uncomplicated and easily automated. For this reason, structure and function of the valved stopper and separator are sufficiently independent that the separator can be affixed to the valved stopper in any angular orientation relative to the plane of a slit in the valved stopper. 
         [0063]    In an application for a multi-chamber syringe, a very toxic liquid (e.g. chemotherapy agents) may be stored in the distal chamber near the distal syringe orifice. To protect against inadvertent contact with such toxic liquid, it is preferred to provide some kind of a buffer. A novel addition to a multi-chamber syringe in the form of a tube set provides such a buffer. The tubing set comprises an elongated tube having a syringe connector (such as a luer fitting) on a proximal end and a gas separator assembly on the distal end. The tube is mostly filled with a buffer liquid, the liquid being separated from contents of the distal chamber of the syringe by a trapped air bubble. The gas separator assembly comprises a separator component to trap and filter out the air bubble and a fitting (such as a luer fitting) for connecting to downstream patient lines. 
         [0064]    In summary, the valve assembly:
       provides a selective partitioning between proximal and distal chambers of a multi-chamber syringe.   may be used in conventional (off the shelf) commercial syringes having constant diameter hollow barrels.   filters gas (e.g. air) from liquid delivered from the proximal chamber.   permits the distal chamber of the syringe to be used in the same manner as a conventional syringe prior to dispensing fluid from the proximal chamber.   in a preferred embodiment, provides a closed, bi-stable valve which is opened only after collision between the valve assembly and inner surface of the distal end of the syringe and which remains in an open state once opened.   has a valved stopper/separator interface which acts as a clinch to maintain a slit of the valved stopper closed until opened at the distal end of the syringe.   requires a tactilely sensible force to open the valve of the valved stopper after collision of the valve assembly with the distal end of a syringe.   does not displace fluid proximally at an end of a proximal chamber dispensing cycle, thereby permitting the device to operate reflux free.   separates gas from liquid and only dispenses liquid from the proximal chamber.   comprises parts which stabilize the valve assembly throughout displacement.   permits the valve to open only upon contact with a distal end of a syringe or other stop within the barrel of the syringe       
 
         [0076]    Accordingly, it is one object to provide a valve assembly which partitions a conventional commercial syringe to make a multi-chamber syringe. 
         [0077]    It is another object to provide a valve assembly for a syringe which keeps two disparate fluids apart until one of the fluids has been dispensed from the syringe. 
         [0078]    It is another object to provide a valve assembly which has a low dead space for liquid dispensed from a distal chamber. 
         [0079]    It is another object to provide a valve assembly having an operable slit valve. 
         [0080]    It is another object to provide a valve actuator within a valved stopper which senses collision between a valve assembly and an inner surface at the end of a syringe (or other stop within the syringe barrel) and an increased pressure across the valved stopper to force a valving slit open. 
         [0081]    It is another object to provide a bi-stable valve as part of the valved stopper. 
         [0082]    It is another object to provide a valve assembly which opens to dispense liquid from a proximal chamber only after liquid from a distal chamber has been dispensed. 
         [0083]    It is another object to provide a valve assembly which acts as a liquid filter in the proximal chamber to deter gas from being dispensed from the proximal chamber. 
         [0084]    It is another object to provide a separator which is a stabilizer for an associated valved stopper in a syringe barrel. 
         [0085]    It is an object to provide an interface between a valved stopper and a separator such that displacement of the valved stopper likewise displaces the separator. 
         [0086]    It is an object to provide a multi-chamber syringe having a front chamber which may be used in the same manner as a conventional syringe prior to dispensing fluid from the proximal chamber. 
         [0087]    It is a further object to provide a multi-chamber syringe combination which comprises the multi-chamber syringe disclosed supra plus an attached tubing set whereby three disparate liquids may be kept disparate and dispensed sequentially. 
         [0088]    These and other objects and features of the present invention will be apparent from the detailed description taken with reference to accompanying drawings. 
     
    
     
       DRAWINGS 
         [0089]      FIG. 1  is a perspective of an exemplary commercial syringe with a plunger and stopper assembly disposed within the barrel of the syringe (prior art). 
           [0090]      FIG. 1A  is a section of the syringe seen in  FIG. 1  taken along lines  1 A- 1 A (prior art). 
           [0091]      FIG. 2  is a section of a syringe, similar to the section seen in  FIG. 1A , but with a valve assembly, as disclosed in Howlett, distally disposed relative to a plunger and stopper similar to the plunger and stopper of the syringe of  FIG. 1 . 
           [0092]      FIG. 2A  is a magnified portion, taken along lines  2 A- 2 A, of the syringe seen in  FIG. 2 . 
           [0093]      FIG. 3  is a perspective of the valve assembly seen in the syringe barrel in  FIG. 2 . 
           [0094]      FIG. 4  is an exploded view of the valve assembly seen in  FIG. 3  showing a valved stopper apart from a valve actuator. 
           [0095]      FIG. 5  is a perspective of the valved stopper, seen in  FIG. 4 , rotated such that the distal side of a slit valve is seen. 
           [0096]      FIG. 6  is a perspective of a valved stopper, which is similar to the valved stopper seen in  FIG. 5 , but rotated such that the proximal side of the valve is seen. 
           [0097]      FIG. 7  is a perspective of a valved stopper of the currently preferred embodiment disposed to present a distal face of the valved stopper. 
           [0098]      FIG. 8  is a perspective to the valved stopper seen in  FIG. 7 , the valve being rotated to present a proximal view. 
           [0099]      FIG. 9  is a side elevation of the valved stopper seen in  FIGS. 7 and 8 . 
           [0100]      FIG. 10  is a cross-section of the valved stopper seen in  FIG. 9 . 
           [0101]      FIG. 10A  is a graphical representation of critical operating pressures related to distal displacement and opening of a valve in a valve assembly. 
           [0102]      FIG. 10B  is a graphical representation of critical operating pressures related to proximal displacement and opening of a valve in a valve assembly. 
           [0103]      FIG. 11  is a perspective of a gas separator assembly disposed such that the rear of distal end is seen. 
           [0104]      FIG. 12  is a rear elevation of the gas separator assembly seen in  FIG. 11 . 
           [0105]      FIG. 13  is a perspective of the gas separator assembly seen in  FIG. 11 , but rotated such that the front or proximal end is seen. 
           [0106]      FIG. 14  is a front elevation of the gas separator assembly seen in  FIG. 13 . 
           [0107]      FIG. 15  is a section of the gas separator assembly seen in  FIG. 13 , the section being taken across two medially disposed ribs of the separator. 
           [0108]      FIG. 16  is a side view of a portion of a syringe in which a valve assembly, constructed from the gas separator assembly seen in  FIG. 15  and the valved stopper (in cross section) seen in  FIG. 9 , is disposed. 
           [0109]      FIG. 17  is a side view of the valve assembly seen in  FIG. 16  with a valve portion of the valved stopper seen in a first bi-stable or closed state. 
           [0110]      FIG. 18  is a side view of the portion of the syringe and valve assembly seen in  FIG. 16 , but with a valve portion of the valved stopper seen in a second bi-stable or open state. 
           [0111]      FIG. 19  is a side schematic view of a multi-chamber syringe fabricated according to the instant invention disclosed wherein is seen a valve assembly separating a filled proximal chamber from an empty distal chamber. 
           [0112]      FIG. 19A  is a side schematic view of the multi-chamber syringe seen in  FIG. 19  with the valve assembly disposed in contact with an distal inner surface of a conventional syringe. 
           [0113]      FIG. 19B  is a side schematic view of the multi-chamber syringe seen in  FIGS. 19 and 20  with liquid disposed in the distal chamber of the syringe. 
           [0114]      FIG. 20  is a side schematic view of the multi-chamber syringe seen in  FIG. 19B  with the valve assembly disposed against the distal inner surface of the syringe. 
           [0115]      FIG. 20A  is a side schematic view of the multi-chamber syringe seen in  FIG. 20  with a valve of the valved assembly disposed in an open state. 
           [0116]      FIG. 20B  is a side schematic view of the multi-chamber syringe seen in  FIG. 20  with a valve of the valved assembly disposed in an open state and liquid dispensed from the proximal chamber. 
           [0117]      FIG. 21  is a lateral schematic view of the syringe seen in  FIG. 20B . 
           [0118]      FIG. 22  is a lateral schematic view of the syringe seen in  FIG. 21  with a tube attached and a drop of liquid being emitted from a distal end of the tube. 
           [0119]      FIG. 23  is a side schematic of a multi-chamber syringe with an attached tubing set which contains an additional liquid chamber, liquid in the chamber being maintained disparate from liquid in the distal chamber by a gas bubble. 
           [0120]      FIG. 24  is a side schematic of a multi-chamber syringe wherein an elongated barrel of the syringe comprises two sections, a proximal section being of larger diameter than the distal section, and a valve assembly disposed in the distal section to divide a proximal chamber from a distal chamber. 
           [0121]      FIG. 24A  is a side schematic of the multi-chamber syringe seen in  FIG. 24  with liquid being disposed in each chamber. 
           [0122]      FIG. 24B  is a side schematic of the multi-chamber syringe seen in  FIG. 24  with liquid having been dispensed from the distal chamber. 
           [0123]      FIG. 24C  is side schematic of the multi-chamber syringe seen in  FIG. 24  with a valve of the valve assembly disposed in an open state and with liquid dispensed from the proximal chamber. 
           [0124]      FIG. 25  is a schematic showing a plurality of syringes oriented in a plurality of multi-chamber syringes demonstrating multi-chamber syringes made in accordance with the instant invention may be used in any position relative to gravitational pull. 
       
    
    
     DESCRIPTION 
       [0125]    In this description, primes of numbers are used to represent parts which are similar, but not identical to other parts having the same numbers. Reference is now made to embodiments illustrated in  FIGS. 1-25  wherein like numerals are used to designate like parts throughout. It should be noted that  FIGS. 1-6  are selected from FIGS. disclosed in Howlett and are provided herein for ease of reference. 
         [0126]    Prior art syringes (as exemplified by syringe  10 ) in  FIGS. 1 and 1A , are available from a large number of commercial companies worldwide. Such syringes typically comprise an elongated hollow syringe barrel  20  which is open at a proximal end  22  to receive a syringe plunger  30  and stopper  40  and closed at a distal end  42  about a fluid transmission orifice  44 . Generally, barrel  20  is of substantially constant diameter (within tolerances allowed by manufacturing methods, such as by injection molding for barrels made from synthetic resinous materials). Stopper  40  is compressible and sufficiently elastic when compressed to provide an efficient wiping action along the length of an internal cylindrical surface  46  of barrel  20 . 
         [0127]    As seen in  FIG. 2 , a valve assembly  50  (according to Howlett) is inserted into barrel  20  to divide space within barrel  20  into a proximal chamber  60  and a distal chamber  70 . As seen in  FIGS. 2 and 2A , each chamber,  60  and  70 , may be filled with a volume of fluid,  72  and  74 , respectively. It may be noted that, when chamber  60  is substantially filled with a volume of fluid (which should be mostly an incompressible liquid), displacement of stopper  40  results in substantially the same displacement of valve assembly  50 . It may also be noted that fluid  72  disposed in chamber  60  is trapped and may contain a small bubble of gas, numbered  76 , (which is likely air) associated with other liquid  78  also contained therein. Such gas  76  may be inadvertently trapped therein during filling or may be the result of outgassing or other gas producing phenomena following insertion of stopper  40  into barrel  20 . In any event, such gas should be seriously considered and dealt with when such a device is used to dispense liquid to a patient to assure gas (air) is not injected into a patient line. 
         [0128]    As disclosed in Howlett, a valve assembly  50 , apart from a barrel  20 , is seen in  FIG. 3 . Although more parts may be used in a valve assembly made according to the instant invention, valve assembly  50  comprises just two parts, a valved stopper  80  and a valve actuator  90 . Note that valved stopper  80  has a hollow cylindrical well  92  into which valve actuator  90  is displaced for use. 
         [0129]    Additional details of valved stopper  80  and valve actuator  90  are seen in  FIG. 4 . Valved stopper  80  has an outer cylindrical wall  94  which has a pattern of annular grooves, generally numbered  96 , to facilitate sealingly wiping of inner surface  46  of barrel  20  as valve assembly  50  is displaced therealong (see  FIG. 2A ). Within well  92 , valved stopper  80  comprises a plurality of grooves disposition and purpose of which are disclosed in detail in Howlett from which this application claims priority. 
         [0130]    As seen in  FIG. 4 , valve actuator  90  comprises a proximal stabilizing disk  100 , a medially disposed stabilizing plate  110 , a pair of actuator arms,  120  and  120 ′, a medially disposed support body  130 , into which is formed a gas separator vessel  140  and an annular connecting lip  150 . Note vessel  140  is penetrated by a plurality of holes  270 ′. Valve actuator  90  is displaced into well  92  as indicated by dashed lines  152  and  152 ′. 
         [0131]    Distal end  154  of valve assembly  50  is seen in  FIG. 5 . Note, presence of a slit  160  which is medially disposed through a distal wall  162  of valved stopper  80 . Slit  160  is formed as a closed valve which remains fluid tight until selectively opened by the action of arms  120  and  120 ′ as disclosed in detail in Howlett. As arms  120  and  120 ′ must be aligned with slit  160 , special manufacturing methods, as also disclosed in Howlett, are required. Also note, a distal surface disposed annular ring  330  which raises that surface to collide with the inner surface of the distal end  42  of syringe  10 . 
         [0132]    Greater detail of construction of well  92  is seen in  FIG. 6 . Valved stopper  80  has a plurality of grooves and associated slots, each of which serve a specific purpose. However, there are no grooves for rim  172  of disk  100  and outer edges  182  and  182 ′ of plate  110 . (See  FIG. 4 .) Such grooves would impede distal displacement of valve actuator  90  within valve stopper  80 . Such distal displacement is necessary for valve action, as is disclosed in detail in Howlett. A groove  190  (see  FIG. 6 ) coincides with protrusions  192  and  192 ′ of arms  120  and  120 ′ (see  FIG. 4 ), respectively. A slot  200 , disposed on the inner side  202 , of distal wall  162 , coincides with extremities  204  and  204 ′ of arms  120  and  120 ′ (again see  FIG. 4 ). Finally, an annular slotted groove  210  is also disposed on the inner side  202  of distal wall  162  to coincide with annular connecting lip  150 , also seen in  FIG. 4 . 
         [0133]    Of significant concern in valve assembly  50  is the requirement for a required alignment between slit  160  and arms  120  and  120 ′. Such an alignment requires special manufacturing methods as disclosed in Howlett and complex part handling during assembly of valve actuator  90  into valved stopper  80 . As one skilled in molding and part assembly arts understands, there are a number of advantages of the presently preferred embodiment. For example, as is disclosed in detail hereafter, the part associated with gas separation of the currently preferred embodiment is more easily molded, the slit is more easily made, separate from other manufacturing procedures, in the valved stopper and the two parts are more easily assembled because there is no specific angular orientation of the gas separator relative to the slit. 
         [0134]    Reference is now made to  FIGS. 7-25  wherein various details of the current preferred embodiment are seen. Initial reference is made to  FIG. 16 , where a valve assembly  550  is seen disposed within a portion  552  of a barrel  20  of a syringe  10 . As seen in  FIG. 16  syringe  10  ends in a surface or stop  554  having a predetermined concave or frustoconical shape  556  and a medially disposed orifice  44  through which fluid flows (see also  FIGS. 1 and 2 ). Note that valve assembly  550  comprises a valved stopper  580  and a liquid filter or gas separator, generally referenced as separator  590 . As seen in  FIG. 7 , valved stopper  580 , comprises a distal surface  592  and an outer cylindrical wall  594 . Wall  594  has a pattern of annular grooves, generally numbered  596 , to facilitate sealingly wiping of inner surface  46  of barrel  20  as valve assembly  550  is displaced through barrel  20  (See  FIG. 16 .). Distal surface  592  comprises an outer facing ring  598  and a recessed medial portion  600 . Outer facing ring  598  is preferably contoured to conform to an inner distal surface or stop  554  of distal end  42  of syringe  10 . 
         [0135]    Recessed medial portion  600  (see  FIG. 7 ) is bounded by a cylindrical wall  602 , an annular hinge  604 , peripherally affixed to wall  602 , and a medially disposed, non-planar valve  610  affixed to an inner portion of hinge  604 . On a distal surface  612 , a portion of a planar slit  620  is seen to be medially disposed in valve  610 . 
         [0136]    A Self-Actuating Valved Stopper 
         [0137]    Valved stopper  580  is rotated in  FIG. 8  to reveal a hollow cylindrical inner core  622 , a distal interior surface  624  of valve  610 , a portion of annular hinge  604  which circumscribes valve  610  and an annular groove  630 , the purpose for which is disclosed in detail hereafter. Exterior shape and form of valved stopper  580  are seen in  FIG. 9 . Note frustoconical shape of surface  598 , which is shaped to conform with contour of inner surface  554  of distal end  42  of syringe  10  to minimize dead space. 
         [0138]    A cross section of valved stopper  580  is seen in  FIG. 10  to be disposed within a section  632  of a barrel  20 . As such, valved stopper  580  divides space in barrel  20  into a proximal chamber  60  and a distal chamber  70 . A pressure resident in chamber  60  is represented by P p . A pressure resident in chamber  70  is represented by P d . If P p  is not equal to P d , the non-zero pressure gradient is represented by ΔP (i.e. ΔP=P p −P d ). Note, that, if ΔP is positive, the resulting motive force upon proximally facing surfaces  636  of valved stopper urges valved stopper  580  toward end surface  554 . If ΔP is negative, the resulting force upon distally facing surfaces  638  urges valved stopper  580  away from surface  554 . Thus force upon plunger  30  of syringe  10  in a distal direction relative to barrel  20  tends to generate a positive ΔP and a force in a proximal direction relative to barrel tends to generate a negative ΔP. 
         [0139]    Due to the fact that stopper  580  is displaceable within barrel  20 , P p  and the associated ΔP is effectively limited when ΔP produces a force across surfaces  636  which overcomes friction (and stiction) to displace stopper  580 . Note that, if a valve in Stopper  580  is also opened by a predetermined ΔP, a force which overcomes friction to displace stopper  580  must be less than the force which results in opening a valve disposed in valve stopper  580 . 
         [0140]    As seen in  FIG. 10 , stopper  580  comprises a medially disposed, dome-shaped valve  640 . Valve  640  is affixed to the remaining body  642  of stopper  580  via an annular hinge  650 . It should be noted that, while valve  640  is hemispherical in shape, any valve shape which remains closed at a ΔP which displaces stopper  580  distally and which opens at a greater ΔP may be used within the scope of the invention. Such valves are usually non-planar. Further, as is disclosed in detail hereafter, there are important reasons for such a valve to remain open (be bi-stable) once being opened. 
         [0141]    As may be noted in  FIG. 10 , valve  640  has a proximal surface  660  having a radius of curvature  662 , a distal surface  670  having a radius of curvature  672  and a medially disposed slit  680 . Hinge  650  has a thickened portion  682  where hinge  650  is affixed to remaining body  642  of stopper  580  and a thinned portion  684  where hinge  650  is affixed to valve  640 . Thicknesses of hinge  650  and valve  640  determine ΔP necessary to open valve  640 . 
         [0142]    As an example, in a valve made to operate in a stopper for a 20 milliliter syringe, having an internal barrel diameter of approximately 0.8 inches, a valve assembly may be manufactured wherein the diameter of the stopper is increased to a diameter four percent grater than the internal barrel diameter. The proximal surface radius  662  may be approximately 0.25 inches. Thickness of the wall between surfaces  662  and  672  would be nominally 0.040 inches, although a variance of 0.012 may be allowed. Thickness of thickened portion  682  of annular hinge  650  was approximately 0.100 inches. Thickness of thinned portion  684  may be nominally 0.060 inches. Slit  680  is nominally approximately 0.160 inches. 
         [0143]    Reference is now made to  FIG. 10A  which provides a graph o of a positive ΔP versus displacement of stopper  580  in a barrel  20 . Zero ( 0 ) marks an initial stationary point of stopper  580  relative to a point of collision (C) between stopper  580  and surface or stop  554  (see  FIG. 18 ). Dashed line  690  represents a pressure differential necessary to overcome friction (and stiction) to displace stopper  580 . A second dashed line  692  represents a ΔP which forces valve  640  open. Solid line  694  is an example of ΔP as stopper  580  traverses through barrel  20 . Note that ΔP  694  is substantially constant until collision between stopper  580  and surface  554  when ΔP  694  rises sharply to opening pressure differential  692 , then falls rapidly as released flow decreases chamber  60  pressure. Note that any collision with a stop within barrel  20  would result in such a rise in ΔP. 
         [0144]    An opened valve  640  is seen in  FIG. 18 . Note that, once valve  640  is forced to an open state, surfaces  660  and  670  are turned inside out (inverted). Surface  670 , having the smaller radius of curvature of the two surfaces, tends to open slit  680  when dome-shaped valve  640  is inverted. The combination of inherent locking nature of the inverted surfaces and force imposed by annular hinge  650  tends to hold valve  640  in the open state providing a bi-stable valve which is maintained in an open state, once opened. Such a state has a definite advantage in IV therapy and is disclosed in detail hereafter. 
         [0145]    An example of such a valved stopper has been made and tested by West Pharmaceutical Services, 101 Gordon Drive, PO Box 645, Lionville, Pa. 19341. As earlier disclosed, these valved stoppers were made with a diameter which is approximately four percent larger than an inner diameter of a 20 ml syringe barrel in which they were disposed. With such a design, pressure to slide a siliconized stopper was in the range of 2.4 to 5.6 pounds (generally about three to four pounds). Pressures to open the valved stoppers ranged from 12.50 to 22.2 pounds. While such pressure ranges may vary due to size and material factors, these pressures may be considered representative of pressure differentials evidenced in valve actuation. Material used in stoppers associated with these tests was West Formulation 4023/50 Gray. 
         [0146]    A problem associated with a non-planar valve, when employing a syringe  10  to withdraw fluids into a front chamber  70  (as is done with a conventional syringe), is a tendency of the valve (e.g. dome-shaped valve  640 ) to “balloon” when ΔP is negative. Such ballooning tends to open slit  680  to open permitting cross-contamination of contents of chambers  60  and  70 . As seen in  FIG. 10B , a negative ΔP as indicated by dashed line  696  may be commonly disposed across valve  640  (as an example to fill chamber  70 ). Ballooning, opening an unclinched slit  680 , may commonly occur at a smaller negative ΔP, indicated by dashed line  698 . To solve this problem a restraint should be disposed about surface  660  in the form of a clinch to maintain slit  680  closed. For this and other purposes, a separator component (generally referenced separator  700 ) having a clinch, as seen in detail in  FIGS. 11-15 , is firmly affixed to stopper  580  about valve  640 . 
         [0147]    A Separator, Stabilizer and Clinch 
         [0148]    Separator  700  is similar to actuator  90  (see  FIG. 4 ). However separator  700  is not required to comprise arms  120  and  120 ′ because stopper valve  640  is self-actuating and is inherently bi-stable. A set of orthogonally disposed wings, generally numbered  710  (see  FIGS. 13 and 14 ), are proximally disposed on a frustoconically shaped body  712  of separator  700  to provide stabilizing support when separator  700  is affixed to stopper  580  and disposed in a barrel  20 . These wings  710  replace disk  100  and plate  110  of actuator  90  (see  FIG. 4 ). Structure of holes, generally numbered  270 ′ (see  FIG. 15 ), is relatively unchanged from actuators disclosed in Howlett, except for a plurality of holes  270 ″ disposed through a proximal face of separator  700  (see  FIGS. 13 and 14 ). Holes  270 ′ and  270 ″ provide a low resistance pathway for liquid and a much higher resistance pathway for gas (air), thereby forming an effective liquid filter, filtering gas from dispensed liquid as do holes  270 ′ of actuator  90 . 
         [0149]    On a distal side  714  of body  712  (see  FIG. 11 ) separator  700  has an open throat  716 . Disposed about throat  716  is a structure which forms an annular lip  720  (see  FIG. 11 ). Referring once more to  FIG. 10 , stopper  580  is seen to have annular groove  730  disposed about dome valve  640 . Lip  720  (see  FIG. 11 ) and groove  730  comprise complementary shapes such that lip  720  fits into groove  730  to securely and sealingly affix separator  700  to stopper  640  to form a valve assembly  740  (see  FIGS. 16-18 ). 
         [0150]    As may be best seen in  FIG. 11  body  712  comprises a plurality of medially directed ribs, generally numbered  750 . Each distal surface  752  of each rib  750  comprises a curvature which is similar in size and radius of curvature of exterior surface  660  (see  FIG. 10 ). However, in combination, surfaces  752  each have a sufficiently smaller radius of curvature  754  (see  FIG. 15 ) than radius of curvature  660  to act as a clinch against proximal surface  624  of domed valve  610 . Thus, in combination ribs  750  form a clinch  780  (see  FIG. 15 ) which acts to maintain slit  680  (see  FIG. 10 ) in a closed state when separator  700  is affixed to valved stopper  640  and a ΔP across dome valve  640  is negative. 
         [0151]    A Valve Assembly 
         [0152]    Valve assembly  740  may be seen in various dispositions in  FIGS. 16-18  with separator  700  securely affixed to valved stopper  640 . In  FIG. 17 , separator  700  is shown as transparent, permitting dome valve  640  to be clearly seen. In  FIG. 16 , valve assembly  740  is disposed proximally apart from surface  554  such that slit  680  (see  FIG. 17 ) remains closed keeping fluids residing in chambers  60  and  70  disparate. In  FIG. 18 , valve assembly  740  is disposed against a stop provided by surface  554  with sufficient force being exerted upon an associated plunger to create a sufficiently large positive ΔP to invert dome valve  640  and open slit  680 . Note that indentation of dome valve  640  a distance defined by the width of wall  602  (see  FIGS. 8 and 18 ), permits valve  640  to bulge outward upon opening without conflicting with surface  554 . 
         [0153]    Various modes of use of valve assembly  740  in a syringe  10  are seen in  FIGS. 19 ,  19 A-B,  20  and  20 A-B. As seen in  FIG. 19 , valve assembly  740  is disposed to divide syringe  10  into two disparate chambers  60  and  70 . A fluid comprising mostly liquid is disposed in chamber  60  while chamber  70  is empty. In  FIG. 19A , a plunger  30  is displaced distally to likewise displace valve assembly  740  to empty chamber  70 . Note that valve  640  (see in  FIG. 17 ) remains closed as tactile and visual senses permit valve assembly  740  to be displaced to completely empty chamber  70  without activating (opening) valve  640 . In  FIG. 19B , plunger  30  is displaced proximally to withdraw liquid  790  into chamber  70 , just as might be done with a conventional syringe without a valve assembly  740 . 
         [0154]    As seen in  FIG. 20 , plunger  30  has been displaced to cause valve assembly  740  to dispense liquid  790  from chamber  70  (see  FIG. 19 , as chamber  70  is totally evacuated in FIGS.  20  and  20 A-B). However, note that a small residual of liquid  790  still resides in orifice  44 . Flushing of such liquid  790  from orifice  44  and other spaces within a patient delivery system is one significant reason for using a multi-chamber syringe. Further an additional force disposed upon plunger  30  effectuates opening of valve  640  as seen in  FIG. 20A . 
         [0155]    Continued application of distally directed force upon plunder  30  dispenses a large measure of the liquid content  792  of chamber  60 . Note that any gas  76  (see  FIGS. 2A and 20B ) which was originally disposed in chamber  60 , remains in chamber  60  and is not dispensed but remains with an undelivered portion of liquid  792 . As seen in  FIG. 25 , a syringe  10  with a valve assembly  740  may be dispensed per the arrows, generally numbered  794  seen in  FIGS. 19 ,  19 A-B,  20  and  20 A-B in any orientation relative to gravitational attraction without dispensing undesirable portions of gas  76  from chamber  60 . 
         [0156]    Reflux-Free Operation 
         [0157]    A magnified and rotated view of syringe  10  and contents seen in  FIG. 20B  is seen in  FIG. 21 . It is important to note that plunger  30  has a catch  796  which inhibits plunger  30  from contacting valve assembly  740 , thereby leaving a fluid buffer  798  disposed between plunger  30  and valve assembly  740 . Due to contents of elastic material (e.g. gas or a rubber stopper of plunger  30 ) and due to valve  640  remaining in a bi-stable state whenever plunger  30  stops, a small positive flow continues to be dispensed from syringe  10 . There is no negative flow allowed due to memory of the elastic material. For this reason, rather than reflux flow into a connected line  800 , seen in  FIG. 22 , a small amount of liquid (seen as droplet  802 ) continues to be dispensed each time plunger  30  stops after valve  640  is open. 
         [0158]    A Three Chamber Multi-Chamber Syringe 
         [0159]    On occasion it may be desirable to dispense a toxic medicine  810  from chamber  70  of a multi-chamber syringe made from a syringe  10  and valve assembly  740 . In such a case, any contact through orifice  44  could be dangerous to a clinician or care giver. In such a situation, it would be preferable to provide an additional distal buffering capacity to provide an increased safety factor. 
         [0160]    A combination  820  for such a purpose is seen in  FIG. 23 . Combination  820  includes a syringe  10  and a valve assembly  740  which divides barrel  20  into chambers  60  and  70 . Syringe  10  is connected to a tubing set  830  comprising an elongated tubing shown in two parts  832  and  834  connected by a dashed line  836  for clarity of presentation. A buffer solution  840  which is hazard free is disposed within tubing set  830  such that any initial fluid dispensed from combination  820  will not be dangerous. To keep contents of chamber  60  disparate from solution  840 , a gas (air) bubble  850  is disposed in a proximal portion of tubing set  830 . It is well known in fluid processing art that such an air bubble will keep liquid, on opposite sides of the air bubble, disparate, thereby maintaining integrity of contents of chamber  70 . Of course, gas (air) should not be dispensed from combination  820 . For this reason an additional liquid filter  700 ′ having similar filtering holes as those disclosed for separator  700  is provided in a chamber  852  disposed at a distal outlet portion  854  of tubing  834 . Note also, that a preferable tubing connector  856 , such as a luer fitting, is comprised within chamber  852  distal to filter  700 ′. In this manner, a multi-chamber syringe is increased in scope to a three chamber combination, with the third chamber being provided by tubing set  830 . 
         [0161]    A Precisely Fillable Multi-Chamber Syringe 
         [0162]    In some applications of multi-chamber syringes, it is desirable to accurately fill a distal chamber, such as chamber  70 , with a small volume liquid dose. Syringe barrels, such as barrel  20  may be too large to permit facilely derived, precision, small dose measurements. For this reason, a syringe, such as syringe  10 ′, seen in FIGS.  24  and  24 A-C, may be employed with a modified valve assembly  740 ′. Syringe  10 ′ has a contiguous barrel which is divided into two sections, a proximal section  20 ′ and a distal section  20 ″. Proximal section  20 ′ is easily seen to be larger in diameter than distal section  20 ″. Valve assembly  740 ′ comprises two parts, a valved stopper  640 ′ and a separator  700 ″. Note that a plunger  30  with an associated stopper is disposed and displaced within proximal section  20 ′. Valve assembly  740 ′ is disposed distal section  20 ″. Valve assembly divides syringe  10 ′ into two chambers, proximal chamber  60 ′ and distal chamber  70 ′. Of course, it is important that valve assembly  740 ′ be perpetually retained in section  20 ″. 
         [0163]    It should be noted that, due to the relatively reduced diameter of section  20 ″ relative to the diameter of section  20 ′, for each unit of distance plunger  30  is displaced, valve assembly  740 ′ is displaced a greater distance. To assure that valve assembly  740 ′ is not extricated from section  20 ″ by displacing plunger  30  too great a distance proximally, separator  700 ″ is sufficiently elongated to contact a most distal portion of plunger  30  before valved stopper  640 ′ is pulled from section  20 ″. Because valve assembly  740 ′ moves farther than plunger  30  in either direction, such contact effectively forms a lock which assures valve assembly  740 ′ remains in section  20 ″ (see  FIG. 20A ). Separator  700 ″ comprises liquid filtering holes and features which affix separator  700 ″ to valved stopper  640 ′ in a manner similar to holes and features of separator  700  is affixed to valved stopper  640 . 
         [0164]    Note that a set of finely placed indicia  860  are imprinted upon a side of section  20 ″ to facilitate precise measurement of liquid withdrawn into section  20 ″. Dispensing of liquid from syringe  10 ′ using valve assembly  740 ′ is the same as dispensing liquid from syringe  10  using valve assembly  740 . As may be noted in  FIG. 24B , plunger  30  is displaced to force valve assembly  740 ′ to be stopped at the distal end of syringe  10 ′. When thereat, additional force opens a slit valve of valved stopper  640 ′ and liquid is dispensed therethrough. 
         [0165]    This invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of this invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.