Abstract:
An automated fluid formulating system for use in small scale laboratory operations. The system utilizes a computer to provide precise control over the measurement of ingredients and the entire formulating process. The novel feature of this invention is that it can provide precise control over the formulating of high viscosity, high solid fluids, such as emulsions and gels. Further, a pre-programmed cleaning cycle can be input into the computer to automatically clean the mixing elements so that the mixing elements do not contaminate subsequent formulations with materials from the prior formulation.

Description:
CROSS REFERENCE TO RELATED PATENT APPLICATIONS 
   This is a non-provisional application of prior pending U.S. provisional application Ser. No. 60/373,285 filed Apr. 17, 2002. 

   The present invention relates to a system for the preparation of fluid formulations. Specifically, it relates to small scale equipment, such as might be utilized in a laboratory, for the preparation of small quantities of fluid formulations. The invention integrates a computer with the mechanical formulation equipment to provide an accurate and reproducible method for the preparation of these fluid formulations. 
   BACKGROUND OF THE INVENTION 
   Small or laboratory scale automated fluid formulating devices are known in combinatorial chemistry operations, the pharmaceutical industry, and in high throughput screening systems used in agricultural and other such similar research areas. The common thread through all of these areas of technology is that the fluids they deal with have very low solids and very low viscosities. These fluids, as typified by water, have viscosities that are independent of the shear rate and generally have viscosities of 1 centipoise. These are referred to as Newtonian fluids because their viscosities are shear independent. 
   When attempting to formulate high viscosity, high solids fluids, such as slurries and colloids, certain inherent design and processing elements preclude the use of equipment which is commonly used for processing Newtonian fluids. When the fluid is Newtonian, the dispensing and mixing system can consistently and accurately measure whatever amounts might be called for. Problems result from the fact that non-Newtonian fluids, such as slurries and gels, are very shear sensitive. When high viscosity, high solids fluids are subjected to the shear forces caused by forcing these types of fluids through tubing under pressure, the viscosities of such fluids will change. This alteration in viscosity is unpredictable and will impact the measurement of the fluids moving through the tubing. Shear variations can distort volumetric measurements of these fluids. Since devices that measure out quantities of fluid ingredients based on volume are very sensitive to changes in viscosity, the accuracy of each measured aliquot cannot be assured, whether it&#39;s for a single dose in a specific formulation or for repeated doses in multiple formulations. The final formulation sample might therefore not correspond exactly to the desired formulation. 
   It is also important for the proper functioning of volume sensing systems that they remain free of fouling or clogging of their internal components. The cleaning of mixing devices designed for use with low viscosity, low solids fluids may be accomplished with ease. Cleaning is simply achieved by flushing internal components with water or a suitable solvent. Another problem that must be addressed when processing high viscosity, high solids fluids in the system described above relates to the issue of cleaning. High viscosity, high solids fluids will form films on the internal surfaces of the components of fluid dispensing and mixing systems designed to process low viscosity fluids. These films are very difficult to remove by simple flushing. Disassembly of the clogged components is often the only way to remove these deposits. Even this process, however, is only of value for a relatively short time because deposition will occur over and over. If not kept clean, these material deposits on internal tubing or at the dispensing nozzles will severely restrict or completely stop the flow of fluids. Since these types of systems are volume sensitive, the film buildup will displace free flowing fluid. The inaccurate measurement of ingredients will then result, producing a formulation product which will not correspond to the desired formulation. The operator may not, if ever, become aware of this problem until numerous quantities have already been dispensed. 
   An attempt to resolve some of the aforementioned problems is manifested in a machine used for processing high viscosity colorants for paints. It is commonly referred to as a tinting machine and may be found in the paint department of a hardware store. This type of machine uses high pressure pumps to move high viscosity fluids. While changes in the viscosities of the various tints may be acceptable in a paint tinting operation, such viscosity variances, which then might cause inaccurate volumetric measurements, cannot be tolerated in a precision fluid formulation generating system. 
   Further, the number of ingredients which can be used as formulation precursors in devices such as tinting machines is limited by the maximum number of dispensing vessels that can be installed onto the device. If a change in one of the ingredients is required, the entire dedicated pump, fluid reservoir and tubing system would have to be removed and cleaned, which is very time and labor intensive. The ability to work with a large variety of fluid precursor ingredients is therefore severely restricted. 
   What is therefore needed is an automated fluid formulating system which can accommodate the processing of a great number and diversity of fluid precursor ingredients required to prepare high viscosity, high solids fluid formulations. The fluid formulating system must be able to accurately measure quantities of shear sensitive, high viscosity fluids, must be easy to clean when changing from one formulation to another without having to disassemble any part or section of the device. 
   SUMMARY OF THE INVENTION 
   In one aspect, the present invention features an automated system for the production of small scale quantities of high viscosity, high solids fluids. The system consists of the mechanical equipment needed to transport liquid precursor ingredients from their respective storage vessels to a mixing vessel. The system is controlled by a computer which regulates the delivery of precise amounts of precursor ingredients into the mixing vessel. Formulating data is input into the computer, which then sends output signals to the mechanical transport equipment to deliver the desired amounts of formulation ingredients to the mixing vessel. Sensors can be incorporated into the mixing vessel to monitor numerous physical properties of the fluid formulation as it is being mixed in real time so that, if needed, changes can be instantaneously made to the formulation recipe and/or processing cycle in order to optimize the desired physical characteristics of the desired fluid formulation. 
   The system of the present invention solves the problem of working with shear sensitive fluids by utilizing a combination of tubing, pumps and sensors designed to measure out precursor formulation ingredients based on the mass of the fluid being dispensed rather than its volume. Further, the sensor can measure other physical characteristics of the fluid formulation and make adjustments to the recipe or process as required. 
   The disruptive and time consuming process of cleaning the mixing equipment is solved by the present invention by pre-programming into the recipe process a cycle whereby the mixing components are first removed from the mixing vessel after each unique formulation recipe is produced and then conveyed to a cleaning vessel. Once the pre-programmed cleaning cycle has been completed, the computer will direct the mixing components back to the mixing vessel to help process the next formulation. During this automated cycle, no operator involvement is required. Further, by having dedicated tubing lines for each formulation precursor and having the fluid components sealed within their respective tubing lines, neither the tubing or the pump requires downtime for cleaning. 
   A second aspect of the present invention is a method for the preparation of small scale quantities of high viscosity, high solids fluids. Because the method is highly automated, it eliminates the need for unnecessary operator supervision, significantly improves the consistency of multiple batches of the same formulation and, by simplifying and expediting the cleaning process, markedly reduces the amount of time required to change from one formulation to the next. 

   
     DETAILED DESCRIPTION OF THE DRAWINGS 
       FIG. 1  is a general schematic of the entire fluid formulating system of the present invention. 
       FIG. 2  is a top plan view of the pump means showing multiple flexible conduits and their corresponding flow restrictors taken along line  2 — 2  of  FIG. 1 . 
       FIG. 3  is a close up cross-sectional view of one of the flow restrictors actuated to restrict the flow of fluid through its corresponding flexible conduit. 
       FIG. 4  is a side view of part of the fluid formulation system of the invention which shows the mixing vessel and the cleaning chamber. The mixing means is inserted into the cleaning chamber. 
   

   DESCRIPTION OF THE INVENTION 
     FIG. 1  shows a system for making fluid formulations according to the present invention. The formulations that may be prepared by this system are high viscosity, high solids fluids. Examples of such fluids are emulsions, gels and colloids, which may have viscosities up to and including 10,000 poise. 
   The system is preferably used in a laboratory scale operation where, perhaps for evaluation and comparison purposes, many different fluid formulations must be prepared, each one differing from another by only minor changes in various physical properties, such as viscosity, mass, volume and pH. Alternatively, multiple samples of the same formulation could be prepared in this way with very exacting precision. 
   Each formulation would take considerable time to prepare when done by conventional means. Each separate precursor ingredient would have to be carefully measured, the mixing would have to be carefully monitored, perhaps requiring sample removal at various times in the commingling and mixing phases to insure that the desired final fluid properties are achieved. 
   The present invention combines the independent feeding of the various formulation precursor ingredients with an automated computer control system. An added feature of the automated computer control system is the real-time monitoring of the physical properties of the fluid formulation while mixing is occurring. Computer regulation, and if needed, feedback monitoring, of each precursor ingredient insures that the final fluid formulation is as close as practicable to the desired formulation. Precise repeatability is also an added benefit when multiple samples of the same formulation must be prepared. 
   Referring again to  FIG. 1 , the paint system consists of a plurality of flexible conduits  12 ,  14 ,  16  and  18 , each having an inlet end  20 ,  22 ,  24  and  26 , respectively, and an outlet end  28 ,  30 ,  32  and  34 , respectively. While only four flexible conduit lines and their related equipment are shown, this is done solely for exemplifying the invention. It should be understood that more or less may be utilized in practice as required. These flexible conduits are operatively disposed within at least one of a plurality of pump means  36 . Pump means are well known in the art. Various types of pumps may be employed in the practice of the present invention. Some suitable examples are progressive cavity pumps, such as those available from Moyno or Seepex, Peristaltic pumps, commercially available from MasterFlex and Watson-Marlow, syringe pumps, which are available from Sage and Harvard, diaphragm pumps, which may be acquired from KNF, gear pumps, available from Micropump and piston pumps, which are commercially available from Fluid Metering Inc. For the sake of merely exemplifying and not to limit the scope of the present invention only a single peristaltic pump is shown. For a more detailed description of representative peristaltic pumps, reference may be made to U.S. Pat. Nos. 4,025,241 and 4,365,943. 
   Each inlet end of each flexible conduit is disposed within one of a plurality of storage vessels  38 ,  40 ,  42 , and  44 . Each of these storage vessels contains a different liquid precursor ingredient, or combination of ingredients, which when mixed together will make up the desired fluid formulation. 
   The outlet ends  28 ,  30 ,  32  and  34  of the plurality of flexible conduits are positioned so as to deliver into a mixing vessel  46 , each of the precursor ingredients respectively contained therewithin. The pump  36  is positioned between the storage vessels  38 ,  40 ,  42  and  44 , and the mixing vessel  46  in order to facilitate the transfer of a precise amount of each of the precursor ingredients from its respective storage vessel into the mixing vessel  46 . 
   The single peristaltic pump  36 , as shown in  FIGS. 1 and 2 , consists of evenly spaced rollers  37   a,    37   b,    37   c,    37   d,    37   e  and  37   f  configured in a cylindrical shape equidistantly spaced around a central drive axle  136 . Motor  137  drives axle  136  in a circular motion so that rollers  37   a  through  37   f  rotate around the axis of axle  136 . Flexible conduits  12 ,  14 ,  16  and  18  are positioned over the rollers of the pump  36 . 
   Each flexible conduit  12 ,  14 ,  16  and  18  is securely affixed to its own bracket assembly  13 ,  15 ,  17  and  19 , respectively. Each bracket is disposed within a housing  21  and is capable of moving in a generally vertical direction under the independent control of a solenoid, a hydraulic system, pressurized gas or similar such means (hereinafter, “activation means”),  131 ,  151 ,  171  and  191 , respectively. Activation means  131 ,  151 ,  171 , and  191  are independently controlled by a computer  62  through lines  132 ,  152 ,  172  and  192 , respectively. When each activation means  131 ,  151 ,  171 , or  191  is activated, its respective bracket is urged in the direction of the pump  36 . At the points of contact with the rollers  37   a,    37   b,    37   c,    37   d,    37   e  and  37   f,  the flexible conduits  12 ,  14 ,  16  and  18  are compressed, thereby restricting the flow of fluid while at the same time creating pockets of fluid between adjacent points of contact with each roller. When pump  36  is engaged, the rollers roll along the flexible conduits and move these pockets of fluid sequentially in a generally linear direction toward the mixing vessel  46 . The pump  36  may also be run in reverse in order to return any one or all of the precursor fluids to their respective storage vessel if the formulation process has been completed or if one or more of the fluid precursors is to be exchanged for another fluid precursor. 
   Within the mixing vessel  46  is located means  56  for mixing the precursor ingredients to create the desired fluid formulation. The mixing means  56  which may be utilized in the practice of the present invention is one that is suitable for operation with small scale, laboratory equipment. Examples of such mixing means include overhead mixers, such as those available from Cole-Palmer Servodyne and IKA Laboratories, magnetic stirrers, such as might be acquired from Corning, rotor-stator homogenizers, available from PowerGen, sonic homogenizers, commercially available from Thomas Scientific, and vortex mixers, available from Cole-Palmer. Solely for exemplary purposes and not to limit the scope of the invention, an overhead mixer is represented in  FIG. 1 . As shown, mixer  56  consists of a motor  80  connected through shaft  82  to one or more stirring blades, generally shown as  84 . Mixer  56  is affixed to support bracket  88 . Linear actuator and control means  86  regulates the vertical and lateral motion of the mixer  56 . Linear actuator and control means  86  may consist of a stepper motor, a solenoid or a hydraulic valve. Linear actuator and control means  86  is capable of completely retracting mixer  56  from any contact with the mixing vessel  46 . 
   Computer  62  is programmed to control the various process steps of the fluid formulating system of the present invention. The recipe, as it is commonly referred to, of the desired or hypothetical fluid formulation(s) is input into the database of computer  62  by various means such as manually by an operator, or from other database systems to which computer  62  is connected, such as a LIMS system (Laboratory Information Management System) or an expert system which is commonly used in coatings operations. 
   Another benefit of using a computer to control the fluid formulation system is that it may be programmed to monitor the entire formulating process and make adjustments to the rate of addition of the various precursor ingredients or to adjust the amount(s) of one or more of these ingredients. During mixing, it may be beneficial to monitor various physical properties of the fluid formulation as it is evolving. This is referred to as a feedback loop. Too much of one ingredient or not enough of another may totally alter the outcome of the desired formulation. Therefore, optionally, a multifunctional sensor means  58  may be installed within the mixing vessel  46  to quantitatively measure one or more of a plurality of physical properties of the fluid formulation. These physical properties are typically the overall mass, volume, viscosity and pH of the fluid formulation. The multifunctional sensor  58  is capable of converting each of the various measured physical properties into a corresponding measured physical property value. Since the sensor  58  may be programmed to operate continuously during the entire mixing cycle, it has the capability of providing a real-time analysis of the fluid as it is being formulated. 
   Attached to the sensor  58  is an electronic sending means  60  which transmits the measured physical property values to computer  62  via wire  61 . As the computer  62  receives continuous feedback information from the sensor  58 , it can generate a real-time analysis of a dynamic process. By dynamic it is meant that the various physical properties of the end product change over time as the various precursor ingredients are being added to the mixing vessel  46 . The computer  62  receives measured physical property values transmitted by the sending means  60  and compares each measured physical property value to its corresponding desired physical property value. The desired physical property values have already been input into the computer database, as described hereinabove. If monitoring of the progress of the fluid formulation is desired by the operator, then the feedback loop between sensor  58  and computer  62  may be activated. 
   One of the most critical physical property values which can be measured by sensor  58  is the dynamic viscosity of the fluid formulation. Dynamic viscosity is a function of the torque resistance exhibited by the fluid as it is being formulated and will range from 1 centipoise to 10,000 poise. Poise is defined as a gram per centimeter second. Dynamic viscosity may also be measured in Pascal seconds, each unit defined as being a Newton second per square meter. For comparative relevance, 1000 Pascal seconds equals 10,000 poise. 
   Whether or not the computer is operating solely on recipe information previously input into its database or is programmed to receive and process information continuously being fed back from the sensor  58  during formulating, the flow of the various precursor fluids through their respective flexible conduits must be carefully controlled. Referring to  FIG. 2 , separate flow restrictors  48 ,  50 ,  52 , and  54  are operatively located on each of the plurality of flexible conduits to regulate the amount of each of the precursor ingredients being delivered to the mixing vessel  46 . Although various designs of flow restrictors may be employed with the present invention, a preferred design, as shown in  FIG. 3 , comprises a valve plunger  49  which is operated by, for example, a hydraulic system, pressurized gas or solenoid means (hereinafter, “valve”)  51 . Each flow restrictor  48 ,  50 ,  52  and  54  is connected to computer  62  by electrically conductive wires  64 ,  66 ,  68  and  70 , respectively. For example, in response to a signal from computer  62 , sent via wire  64  to flow restrictor  48 , the valve  51  is activated thus enabling the valve plunger  49  to forcibly contact and compress flexible conduit  12 . 
   Depending on the directions provided by the computer  62 , the valve plunger  49  may either only partially or completely obstruct the flow of fluid through flexible conduit  12 . If flow in flexible conduit  12  is to be completely closed off, the computer will send a signal to activate flow restrictor  48 , thus completely closing off the flow of fluid therethrough. Simultaneously, the computer  62  will send a signal through wire  132  to direct activation means  131  to retract bracket assembly  13  away from pump  36 , thereby disengaging conduit  12  from contact with the pump rollers  37   a  through  37   f.  At this point, the movement of the specific fluid precursor contained within conduit  12  to the mixing vessel  46  will cease. 
   Alternatively, the computer  62 , either in response to pre-programmed directions or to signals received from the sensor in the mixing vessel, may direct any one of the plurality of flow restrictors  48 ,  50 ,  52  or  54  to only partially restrict the flow of fluid through its respective flexible conduit, thus allowing only a reduced amount of the respective precursor ingredient to flow to the mixing vessel. As determined by the programming data fed into the computer, the addition of the ingredients into the mixing vessel may be performed either sequentially or serially. 
   By activating the feedback loop, the measured physical property values sent back to computer  62  are compared with their corresponding desired physical property values. Based on the difference, if any, between the measured and desired values, the computer  62  may be programmed to determine whether and, if so, how much more of any specific individual precursor ingredient might be needed to produce the desired fluid formulation having the proper balance of physical properties. For example, as the formulation is being mixed, the sensor  58  may detect that the dynamic viscosity is lower than was predicted for that point in the processing cycle. In such instance, more of the precursor ingredient which contains, for example, a thickener might be added to achieve the desired viscosity level. 
   As directed by the pre-programmed formulation protocol, the computer  62  will shut down the entire system once certain predetermined parameters are met, such as total mass, desired viscosity and/or target pH. Alternatively, if the sensor  58  is activated to feed real-time process information back to the computer  62 , then once each of the physical properties which are being monitored equals its corresponding desired pre-programmed physical property value, then the delivery system is shut down. However, it may still be necessary, either according to a pre-programmed protocol or as determined by feedback information, to have the mixer remain on for an additional period of time, in order to satisfy the specific processing requirements for each formulation. 
   An additional essential feature of the inventive fluid formulation system is the ability to automate the process of cleaning the components of the mixer  56 . As shown in  FIG. 1 , adjacent to the mixing vessel is a cleaning chamber  90 . Cleaning chamber  90  contains an internal vessel  92  which holds a cleaning fluid. Any suitable cleaning chamber is within the contemplation of the present invention, such as ultrasonic chambers, agitating devices, internal spray washers or abrasion scrubbers. The cleaning fluid may be anything suitable for cleaning the residue of the fluid which has been formulated from the various surfaces of mixer  56 . Such cleaning fluids may consist of water, hydrocarbon solvents, aqueous surfactants, supercritical fluids or any combination thereof. 
   When a change is made from one type of fluid formulation to another, it is imperative to clean the mixer  56  so that successive fluid formulations are not contaminated by residue from the previous formulation. The computer  62  may be programmed to remove the mixer  56  from the mixing vessel  46  by activating the control means  86  to vertically retract mixer  56  from mixing vessel  46 . Mixer  56  is then moved along support bracket  88  by any conventional mechanical, electoro-magnetic or hydraulic means to a position just over the top of cleaning chamber  90 . When in this position, the control means  86  inserts mixer blades  84  and shaft  82  completely into the internal vessel  92 , as shown in  FIG. 4 . Cleaning chamber  90  is then activated to perform a preprogrammed cleaning cycle. Once this cycle is complete, the mixer is retracted out of the cleaning chamber  90  and is then moved along support bracket  88  to a position directly over mixing vessel  46  to await instructions from computer  62  to enter the mixing vessel and begin its mixing function on a new formulation.