Fluid delivery system and apparatus to perform the same

The present invention is an apparatus and fluid delivery system for automated assays. The apparatus, for example, may be used for western blotting that uses flow lines for multiple reagents. In one embodiment, the present invention comprises a tray base with one or more fixed or disposable trays for testing samples, multiple flow lines, and multiple valves and the system is used for automatic controlled delivery of different fluids from supply vessels to different trays and discharges them to designated reservoirs or sewage system with minimum of operator actions. The system may include air line to assist supply and discharge the fluids and also coupled with measuring vessels with adjustable volume and valves adapted to interface with a valve operating unit with drive means. The system is controlled by a programmable electronic device that controls the preset values and sequences of valves operation to deliver or discharge the selected fluids in any one or more of plural fluid input ports individually or all together simultaneously, by a set of programmable pinch valves assemblies that pinching or releasing multiple of elastomeric flow conduits, used as a pinch member. The valve operating unit may, in one embodiment, be a single drive unit to control all valve assemblies or, as alternative embodiment, attached to the housing individual mechanism.

BACKGROUND OF THE INVENTION

The present invention relates to automated assay apparatus used to rapidly detect, for example, proteins, in the diagnosis of infection or diseases. Currently available automated assay apparatus are overly complicated and use a number of pumps and dispensers to deliver different liquid reagents to the reaction chambers.

U.S. Pat. No. 4,859,419 discloses an apparatus for immunoassay of multiple samples of biological fluids. The apparatus contains valved ports and a pump that delivers through a single conduit the same biological fluids to a plural of test vessels. The test vessels are closely connected to each other and share a single port to receive and discharge all biological fluids. Conventional assay apparatus of this type do not allow different liquid reagents to be applied to different test samples using different protocols for different test samples. Further, delivery of multiple liquid reagents through the same conduit lead to potential contamination between different liquid reagents that is not acceptable for most types of tests.

U.S. Pat. No. 5,567,595 discloses an automated blot assay apparatus. This apparatus comprises a rocking tray to assure a mixture of the reaction components and for draining simultaneously of all reaction chambers of a tray to remove solution. Thus requires using only one predetermined schedule for all reaction means. Each solution has its own pump and movable dispenser that makes the programming means and construction complex and requires special features to avoid cross-contamination of solutions. Also, for some assay procedure for better mixture of reagents and cover the test samples is preferable to use horizontal agitation of trays which is not possible by applying the method of draining reaction chambers by inclining the tray.

Valves are widely used for control the fluids flow through individually controlled passageways. For example solenoid controlled valves. To use them with different reagents and a numbers of reaction chambers requires dozens of individual valves results in complexity of control and programming means, to produce the apparatus and use them.

Pinch valves and flexible conduits also used in a wide range of apparatus. Some of the known prior art are designed either normally closed or normally open, the control function, accordingly, is to release or to close the passageway. In some applications, most critical for the valves function is the requirement that the passageway through the conduits should be completely open or close.

Other obstacles to use either type of valves is, that in some cases, due the physical properties of elastomeric conduits, different properties of fluids, and contamination, cause the passageway to close, partially or completely, restricting the flow. Also, with pinch valves, when necessary random activation of two or three sets of multiple pinch valves, there should be used multiple activators. This made the control system more complex and requires more space to place them in apparatus. The known prior art includes elastomeric flow conduits and different shapes of plungers or pistons. These require precise machining operations and quite expensive to produce. Some of the known multiple of pinch valves assemble having the multiple flexible flow conduits wherein the activating the pinch action of one of them impede the pinch state of their neighboring conduits and require special features to avoid this. In some of known multiple conduits pinch valves conduits are placed around or near the actuator, the length of the conduits directed to different sites is different and in some cases due the conduits length and liquid properties the valuable liquid will be waste.

SUMMARY OF THE INVENTION

One object of the present invention is the provision the possibility to perform the assay procedure for different testing samples with different time schedules simultaneously.

Another object of the present invention is the provision the possibility to apply to tray either horizontal or rocking agitations.

Another object of the present invention is the provision of better delivery and smaller amount of reagents necessary to perform the reaction.

Another object of the present invention is the provision of multiple pinch valves assemble that allows programmable activation of any number of pinch valves at a necessary sequence of open or close the passageway through the conduits.

Another object of the present invention is the provision of an improved multiple pinch valves assemble which is able to prevent the clogging of passageways through the conduits by completely releasing them during the not working time.

A further object of the present invention is the provision of an improved multiple pinch valves assemble having a simple, standard, and easy to acquire pinch members, to reduce the cost and time to produce parts and assembly the apparatus.

A further object of the present invention is the provision of an improved multiple pinch valves assemble having a simple actuator to open the passageway through the conduits by moving simultaneously multiple or individually one pinch member away from the conduits to facilitate the opening of the passageways.

Another objective of the present invention is the provision of improved multiple pinch valves assemble which controls opening or close of one flow conduits that not affects the opening or close the others.

Still another objective of the present invention is the provision of an improved multiple of pinch valves assembly having a motor and a multi track cam which handle fluids flow through the multiple conduits connected to the fluid sources is a compact device that combines the functions of one, two, or three multiple pinch valves assemblies.

In one embodiment, the present invention seeks to fulfill the need by providing apparatus with relatively fewer components and flexible operation. The invention comprises a tray with one or more fixed or disposable reaction chambers, means to activate tray's either horizontal or rocking agitation motion, multiple valves and automatic control system providing delivery the different fluids from supply vessels to different reaction chambers and discharging them to designated reservoirs according to individual predetermined schedule. The apparatus may include air lines to assist supply and discharge the fluids coupled with measuring vessels with adjustable volume. Valves are adapted to interface with a valve operating unit with drive means activating plural fluid input ports individually or all together simultaneously. The valve operating unit may, in one embodiment, be a single drive unit to control all valve assemblies or, as alternative embodiment, attached to the housing individual mechanism.

DESCRIPTION OF THE INVENTION

The present invention is directed to an automatic apparatus that comprises a multiple of liquid reagent vessels, washer vessels, variable volume measuring vessels, logic control unit, air supply lines, tray with one or multiple reaction chambers agitating either horizontally or rocking, multiple of elastomeric conduits connecting the supply and target vessels, controlled by multiple of pinch valves independently closing or releasing elastomeric flow conduits passageways.

FIG. 1discloses a schematic diagram of the complete system incorporating components comprising the one embodiment of apparatus according to the present invention whereby number1designated the logic control system, PLC,2—a valve drive unit, and3—air pressure supply unit. The following numbers are used to designate other parts of preferred embodiment:2.11to2.14—reagents supply valves,2.21to2.26—washer supply valves,2.31to2.34—tray reaction chambers discharge valves,2.41,2.42,2.44,2.45—air pressure supply valves,2.43,2.46,247—air pressure release valves,5.10to5.40—liquid discharge vessels,7.10and7.20—tray reaction chambers,8.10—washer supply vessel,8.20,8.30,8.40and8.50—reagent supply vessels,9.10and9.20—variable volume measure vessels with9.01and9.02—movable plungers to adjust the required volume of washer liquid, and8.01is sealing lids for all vessels.

FIG. 2illustrates one possible sequence for operating the apparatus. PLC1checks the initial state of the apparatus' components and if all components are ready, starts the process. In this case it is by activating the motor6.40(FIG. 6), starting the tray agitation, horizontal back-and-forth or rocking, and according to the schedule activate the valve drive to open the corresponding valves2.31or2.33to discharge the content of the reaction chambers7.10or7.20. Simultaneously activated air valves2.41and2.46to supply air pressure to8.10and connect chambers7.10or7.20with atmosphere. Further, the table shows the complete schedule, cycle by cycle. There are may be programmed different scenarios.

FIG. 3discloses the preferred embodiment of the major components of the apparatus. A tray7with three reaction chambers, one of them designated7.10, is mounted on the tray platform of the agitating table,6, that can alternatively be set up for a rocking or a shaking movement. A block of supply vessels8is divided on a separate isolated vessels containing washer liquid and a multiple of different reagents. The exemplary embodiment has three, designated8.10,8.20,8.30—for washer, and six,8.40to8.90,—for reagents. All control function are performed by PLC1, and control circuit1.20. The display unit1.10allows change of an existing program or the addition of new one. By2there designated the block of valves and valve drive mechanism,2.10is one of multiple valve assemblies. Air pump3mounted on base4supplies the air pressure to all vessels according to predetermined sequence. Under the tray7is placed a number of discharge vessels5. The number of discharge vessels depends on number of reaction chambers, number of different reagents, and the number of reagents desirable to collect.

FIG. 4illustrates a valve assembly unit that includes six three valves blocks2.10and a valve drive mechanism2.00that designed to activate all valves2.10.FIG. 4adiscloses in greater details the preferred design of the drive mechanism. According to the program, motor2.01rotates the shaft2.06in a position where the pad2.07ais exactly opposite one of the valve actuation bar, for example,FIG. 5, position07. The shaft2.06is fixed with cam2.05and mounted in bearing2.03with the possibility of axial motion. Next, motor2.09rotates the cam2.08and pushes the cam2.05with the shaft2.03forward, and pad2.07afarther pushes the actuation bar07(FIG. 5).

FIG. 5illustrates the exemplary design of the valves. The valve body04has a number, corresponding to the number of valves, studs, designated041, passageways048and rigid vertical abutments043, and one of three guide-way holes049shown on left flange044. Flexible flow conduits, designated A, B, and C threaded through passageways048located on upper flange042and seen only for flow conduit B. Round elongated members01,02, and07are threaded with possibility to move along their axes through three guide-way holes shown in left support flange044. Torsion springs designated03are loosely seated on studs041, with one leg designated032fixed against lugs045of the housing; while the other leg031directed perpendicular to the conduit's axis, pinches the conduit by pressing it to the abutment043, as seen with reference toFIG. 5forming the pressed part of the conduits A1preventing the fluid flow. Further these legs extend through the holes in the elongated members01,02, and07, seen only with elongated member07, designated as071. As seen with reference toFIG. 5when the elongated members07is moved forward, the torsion spring03released the conduit B, opening the elastic conduit going thru passageway and fluid flow.

As seen with reference toFIGS. 5a,5b, and5cthat different surface of the cam06,061,062,063, or064facing three elongated members01,02, and07. Thus, rotation of the cam in either direction causes different independent displacement of each elongated member, which in turn release or press the movable legs031of the torsion springs allow rotation of the spring03around the stud041and compress or release the conduit, allowing the liquid flow or close independently for each set of conduits. The time to rest of the cam in each position determines the volume of fluid flow through the conduit. The position to rotate, the sequence, and time may be easy programmed.

FIG. 6is illustrates the agitating table6. There are four major parts:610—is tray support platform,620—is a base,630—is a rocking bracket, and640—agitating motor. Base620contains a flat bottom621from which extended two protrusions625and626that support the bearings650, a protrusion622that supports agitating motor640, and protrusion623that serves to fix the rocking bracket to the base when the back-and-forth motion of the trays is set up. Tray platform610contains a flat part611from which extended four protrusions612that are serving as supports for two guide bars680that fixed to platform, and protrusion613serving to fix the platform to the rocking bracket when the rocking motion of the platform is set up. The agitating motor640holds an eccentric cam, not shown, that engaged with C shape protrusion614. The rib615is used to hold in place one or multiple of trays. The rocking bracket630holds four bearings670which allow the guiding bars680and the tray's platform slide back-and-forth. Protrusion634serves to fix the rocking bracket630either to base620or to trays platform610changing the type of agitation. For this purpose the special screw690may be engaged with threaded hole in the rocking bracket body or installed in the hole624in protrusion623and screwed up with rocking bracket.

As described heretofore, the present invention is directed to an automated assay apparatus comprising one or multiple assay blocks each of them contains liquid reagents and washer vessels and a tray to support reactant, each of them sealed after filling to be ready for performing assay procedure. The apparatus further comprises means to automatically deliver said reagents and washer liquids into tray of the said block and discharge the reagent and washer liquids from tray into designated vessels in pre-programmed order, for each block independent from others. The apparatus further comprises means providing pre-installed, as desired, horizontal shaking or rocking movements of trays. The apparatus further comprises control means to activate the means to automatically deliver and discharge said liquids to and from each tray undependably, according to preprogrammed sequence. The apparatus further comprises means to control the volume of washing liquid supplied to supply vessels and trays. The vessels and trays comprise a kind of kegs, different sizes and shapes, with sealed lids, connected to each other and to air supply by elastomeric flow conduits and valves. The vessels and trays, in order to facilitate the liquid flow, are supplied with positive air pressure, with simultaneously opening the target vessels' air line to atmosphere. The means to shake trays horizontally or rock them around horizontal axis comprise two guides, a horizontal cross guide-way and a longitudinal axis with bearings, a set of parts to lock either motion, and a DC gear motor with a cam drive. The trays' motions are set up the rocking motion of the trays by locking together rocking bracket and the tray platform, and to set up the horizontal agitating motion of the trays the rocking bracket is locked to the base, unlocking the tray's platform. The means to control the volume of washing liquid comprise sealed chambers, having moving pistons used to pre-install the chambers volume. The chambers are connected to the air line and atmosphere through automatically controlled valves. The valves comprise elastomeric flow conduits initially completely closed by torsion springs that pressing the walls of fluid conduits together onto rigid abutments and serving as pinch members. The means to automatically deliver said reagents and washer liquids into tray of the said block and discharge the reagent and washer liquids from the said trays is a multiple of programmable pinch valves assemblies for control delivery of multiple different fluids from sources to sites by pinching or releasing of elastomeric flow conduits comprising: a housing with plural studs and passageways, multiple elastomeric flow conduits that are threaded through housing passageways, actuator means located in and movable within the housing for acting against the forces of torsion springs to open selected fluid conduits. The valve assembly housing contains plural studs and passageways, and guides as a number of holes in two opposite walls of the housing. The torsion springs are loosely seated on said studs with one leg fixed to the housing, wile the other leg, directed perpendicular to the tube's axis, selectively and individually pinching the conduits preventing the fluid flow. Further this leg extends through the hole in the bar. The torsion springs are loosely seated on the studs to allow easy pivoting the spring around the stud and easy removing it when necessary to change. The backing means are a number of abutments of the housing comprising the vertical walls adjacent to the passageways for elastomeric fluid conduits providing sufficient resistance to accomplish complete closing of the fluid flow through the conduits. The abutments comprise substantially parallel surfaces for support fluid conduits. The studs and spring retaining lugs of the housing placed raw over raw according the number of sets of simultaneously activated multiple of elastomeric flow conduits. The actuator means comprise bars having holes normal to the bar's axis, threaded through and movable along the said housing guide ways. The actuator means comprising bars with holes normal to the bar axis, threaded through and movable along the said housing guide-ways, engaged with the said torsion spring threaded through the said holes. The means to automatically deliver said reagents and washer liquids into tray of the said block and discharge the reagent and washer liquids from the said trays is a multiple of programmable pinch valves assembly for control delivery of multiple different fluids from sources to sites by pinching or releasing of elastomeric flow conduits further comprising a actuator drive that comprise: a shaft located along housing body, a motor that rotates the shaft, a motor with a cam to supply longitudinal motion to the shaft and electrical switches to control the shaft's motions. The shaft bears a number of pads located near actuator's end, said pads translate the shaft's motion, by contacting, to the selecting actuator, to forth the engaged torsion spring to release selected elastomeric flow conduits. The means to automatically deliver said reagents and washer liquids into tray of the said block and discharge the reagent and washer liquids from the said trays is a multiple of programmable pinch valves assembly for control delivery of multiple different fluids from sources to sites by pinching or releasing of elastomeric flow conduits further comprising a actuator drive that comprise: attached to the housing motor and rotatable cam, mounted on the motor's shaft, one or more actuator means, parallel to each other and perpendicular to the cam's axis of rotation, engaged with a number of torsion springs used as a pinch member. The cam has extending radial protrusions which form a cam profile—a displacement profile which placed along the axis of the cam and form a multi track cam, the number of tracks corresponds to the number of flow conduit sets. The cam rotated in either direction imparts the translating motion to the actuator bars which, due to the special contour of said displacement profile, may slide either simultaneously all together or individually in a programmable sequences. When the bar moves it pushes the engaged springs away from the conduits releasing the fluid flow. The valve is programmable by tracks profiles, sequence of cam rotation directions, and the duration of the rotation. The cam actuator contains a number of displacement profiles for activating the movement of cam followers according to desired sequence, activating only one. The cam actuator contains an addition profile track that engaged with electric switch to control the initial position of the cam. The cam followers may contact the cam's displacement profile directly or through intermediate member such as lever, protection.

As described heretofore, the present invention is also directed to a method for automatically deliver reagents and washer liquids into tray and discharge the reagent and washer liquids from the said trays comprising a multiple of programmable pinch valves assembly for control delivery of multiple different fluids from sources to sites by pinching or releasing of elastomeric flow conduits comprising means to automatically deliver said reagents and washer liquids into tray of the said block and discharge the reagent and washer liquids from the said trays is a multiple of programmable pinch valves assembly for control delivery of multiple different fluids from sources to sites by pinching or releasing of elastomeric flow conduits comprising: a housing with plural studs and passageways, multiple elastomeric flow conduits that are threaded through housing passageways, actuator means located in and movable within the housing for acting against the forces of torsion springs to open selected fluid conduits. The means to automatically deliver said reagents and washer liquids into tray of the said block and discharge the reagent and washer liquids from the said trays is a multiple of programmable pinch valves assembly for control delivery of multiple different fluids from sources to sites by pinching or releasing of elastomeric flow conduits comprising: torsion springs serving as a pinch members, contacting the walls of elastomeric flow conduits and pressing them together onto rigid abutments. The means to automatically deliver said reagents and washer liquids into tray of the said block and discharge the reagent and washer liquids from the said trays is a multiple of programmable pinch valves assembly for control delivery of multiple different fluids from sources to sites by pinching or releasing of elastomeric flow conduits comprising: a housing with plural studs and passageways, multiple elastomeric flow conduits that are threaded through housing passageways, actuator means located in and movable within the housing for acting against the forces of torsion springs to open selected fluid conduits. The valves assembly housing contains plural studs and passageways, and guides as a number of holes in two opposite walls of the housing. The torsion springs are loosely seated on said studs with one leg fixed to the housing, wile the other leg, directed perpendicular to the tube's axis, selectively and individually pinching the conduits preventing the fluid flow. Further this leg extends through the hole in the bar. The torsion springs are loosely seated on the studs to allow easy pivoting the spring around the stud and easy removing it when necessary to change. The backing means are a number of abutments of the housing comprising the vertical walls adjacent to the passageways for elastomeric fluid conduits providing sufficient resistance to accomplish complete closing of the fluid flow through the conduits. The abutments comprise substantially parallel surfaces for support fluid conduits. The studs and spring retaining lugs of the housing placed raw over raw according the number of sets of simultaneously activated multiple of elastomeric flow conduits. The actuator means comprising bars having holes normal to the bar's axis, threaded through and movable along the said housing guide-ways. The actuator means comprise bars with holes normal to the bar axis, threaded through and movable along the said housing guide-ways, engaged with the said torsion spring threaded through the said holes.

The foregoing description is intended for purposes of illustration. The invention may be embodied in other forms or carried out in other ways without departing from the spirit or scope of the invention.