Abstract:
Novel apparatuses and methods for depositing or placing substances on substrates or plates are described. The invention relates to automated and semiautomated apparatuses and methods for controlled volume and precise placement of substances on substrates. Combinations of applicator tips, applicator tip assemblies, applicator reservoirs, applicator holders and movable racks precisely and accurately place samples and testing chemicals on substrates. Applicator tips particularly useful for dunk transfer and deposit processes and for carrying substances are disclosed. Apparatuses for precisely moving applicator holders, applicator reservoirs and tips are disclosed. The methods and apparatuses also have features for pre-loading substances on applicators and applicator reservoirs and precisely delivering the preloaded substances to substrates.

Description:
RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Application No. 60/016,933, filed May 6, 1996, which is hereby incorporated by reference. 
    
    
     TECHNICAL FIELD 
     This invention is in the medical and chemical related field. The invention relates to the placing of samples on a substrate. 
     BACKGROUND 
     Scientists and medical technicians are constantly searching for better ways to place, transfer and/or apply samples on various substrates for testing or diagnostic-type purposes. The placement, volume, and dimensions of such samples on a substrate are important to the results of the procedures carried out on the samples. In some instances, improper application of the samples on a substrate will significantly alter or destroy the test results. One such procedure, which is subject to poor results based upon the application of samples, is the procedure of zone electrophoresis. For further background on electrophoresis see, for example, U.S. Pat. No. 5,137,614, issued to Golias on Aug. 11, 1992, entitled “IMMUNOFIXATION ELECTROPHORESIS CONTROL SYSTEM” and incorporated herein by reference. 
     For further background on the application of biological samples for an electrophoresis process, see U.S. Pat. No. 5,405,516, issued to Bellon on Apr. 11, 1995, entitled APPARATUS FOR THE APPLICATION OF BIOLOGICAL SAMPLES TO AN ELECTROPHORETIC SLAB SUPPORT, herein incorporated by reference. 
     Present methods for the automatic application of samples, especially fine samples, to a substrate or flat surface are inadequate. 
     It is an object of the invention improve upon the methods and devices for depositing samples or fluids on a substrate. 
     It is an object of the invention to control the amount of fluid applied to a substrate. 
     It is an object of the invention to control the footprint or shape of the fluid applied to a substrate. 
     It is an object of the present invention to strive to produce a nearly two dimensional deposit of fluid onto a substrate. 
     It is an object of the present invention to provide a semi-automatic and automatic method and device for placing fluid on a substrate. 
     It is an object of the present invention to reduce the risks of damaging the applicator or the substrate during a deposit or delivery. 
     SUMMARY OF THE INVENTION 
     The novel methods and apparatuses for depositing or placing substances on substrates disclosed include applicator tips, applicator reservoirs, applicator tip assemblies, automated and semiautomated apparatuses and processes for using applicators. The methods and other apparatuses are used to automatically or semiautomatically place controlled amounts of substances on substrates. Combinations of applicator tips, applicator tip assemblies, applicator reservoirs, applicator holders and movable racks precisely and accurately place samples and testing chemicals on substrates. Racks and other equipment are used to bring the applicators or transferred substances into contact with the substrates. Preferably racks with vertical movement are used to precisely deposit samples and fluids. 
     Specifically, methods and hardware for applicator tips which carry and deposit sample fluid using lyophilic surfaces are disclosed. Generally, the tips are formed in two parts, one part carries sample fluid and the second part does not. Barriers and other techniques are used to prevent the second part of the tips from carrying fluid. The tips are mounted on applicator holders which are placed on racks and used in automatic and semiautomatic processes. 
     Applicator reservoirs can be used to pre-load substances or fluids for later transfer to substrates. The reservoirs deposit or place controlled volumes of substances or fluids on substrates or plates. The preferred method mixes fluids with polymers to form a gel which is cast in a reservoir. The gel is then placed in contact with a substrate to deposit the fluid. Preferably, these reservoirs are connected to applicator holders which are used in combination with racks and other delivery apparatus. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a front view of the fluid applicator. 
     FIG. 2 is a front view of a multiple applicator tip assembly. 
     FIG. 3 is an enlarged view of an applicator tip. 
     FIGS. 4-11 are enlarged views of different applicator tip configurations. 
     FIG. 12 is a perspective view of an applicator holder with a guard. 
     FIG. 13 is a top view of a single channel supply tray. 
     FIG. 14 is a perspective view of an alternative supply tray. 
     FIG. 15 is a perspective view of a substrate or gel plate. 
     FIG. 16 is a side view of the base and the applicator guide within the application station. 
     FIG. 17 is a perspective view of the applicator guide. 
     FIG. 18 is a perspective view of the applicator rack. 
     FIG. 19 is a perspective view of a chemical delivery system applicator. 
     FIG. 20 is a top view of an automated immuno-fixation electrophoresis system. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     I. Introduction 
     The present invention is a method and apparatus for supporting immuno-fixation electrophoresis or any other type of testing which requires precise and accurate sampling. Generally, the system comprises an application station with a fluid applicator, a chemical delivery system or station with a chemical delivery applicator and a substrate. 
     Generally, the fluid applicator retains a fluid sample for deposit onto a substrate. The application station is a semiautomatic or automatic device for insuring precise deposit of the fluid sample on a substrate. The chemical delivery system applies chemicals or substances to a substrate, and the substrate is the medium for facilitating successful test results. 
     II. Major Subsystems 
     A. Fluid Applicator 
     FIG. 1 shows a front view of a fluid applicator  106 . The fluid applicator  106  comprises an applicator holder  118  and a multiple applicator tip assembly  122  with applicator tips  130 . The applicator tips  130  extend beyond the bottom of the applicator holder  118 . 
     The applicator holder  118  is made of a sturdy material, preferably plastic. Typically, the plastic is styrene. The body of the applicator holder  118  includes a right guide  170 , left guide  174 , and three pins  126 . The two guides  170 ,  174  are used to align the applicator holder  118  within an application station for automatic or semi-automatic application. In the preferred embodiment, one of the guides is wider than other guide to insure the applicator holder  118  is properly inserted into an application station. In alternative embodiments, any difference in the two guides&#39; shape or size can accomplish the same result. If the applicator tip  130  configuration is symmetrical around the central axis  116 , the guides  170 ,  174  may be identical. 
     The three pins or snaps  126  on the applicator holder  118  are used to attach the multi-applicator tip assembly  122  to the applicator holder  118 . The three pins  126  protrude from the applicator holder  118 . The pins  126  may be circular, square, elliptical, or any other shape. The number and position of the pins  126  may vary. In a preferred embodiment, the pin heads are larger than their base. Thus, the multiple applicator tip assembly  122  is attached by aligning holes in the assembly  122  with each pin, and snapping the assembly  122  onto the applicator holder  118 . 
     In alternative embodiments, there are a variety of ways to firmly attach the applicator holder  118  and the multiple applicator tip assembly  122 . For example, they could be attached using double sided tape, heat or ultrasonic sealing, or any common type of adhesive, such as glue. In these embodiments, the holder preferably has a slot or groove to insure the applicator tips  130  are properly positioned. 
     FIG. 2 shows the multiple applicator tip assembly  122 . In the preferred embodiment, the multiple applicator tip assembly  122  is approximately 4½ inches long, 1 inch high, and the width of a piece of paper. The width of the assembly is important because, ideally, immuno-fixation electrophoresis desires a two dimensional line of biological fluid placed on the substrate. The two dimensional line should have a length direction perpendicular to the direction of electrophoretic movement, a depth dimension into the substrate at right angle to the direction of electrophoretic movement, and the smallest possible width dimension. These dimensions directly affect the accuracy of the test results. 
     FIG. 3 shows a single applicator tip  130 . The applicator tip  130  comprises a first portion  140 , second portion  144 , and a blade  147 . The second portion  144  is designed to retain fluid. The first portion  140  is designed to create a barrier  150  which limits the amount of fluid deposited by the applicator tip  130 . The barrier  150  may also be created by the physical or chemical characteristics of the second portion  144 . In alternative embodiments, the barrier  150  limits the amount of fluid retained. 
     In the preferred embodiment, the applicator tip  130  retains fluid from the barrier  150  to the blade  147 . This distance is usually within the range of 0.05 through 0.50 mm. In the preferred embodiment this distance is approximately 0.18 mm. The distance is small because, the smaller the amount of fluid retained by the applicator tip  130 , the easier it is for the fluid applicator  106  to precisely deposit the fluid on the substrate. The barrier  150  can take a variety of forms, such as physical, chemical, electrical, or any combination of these techniques. 
     Some of the common physical barriers  150  are apertures, holes, perforations  148 , or changes in the texture of the surface. These holes  148  may be circular, elliptical, or any other shape. In the preferred embodiment six holes or perforations  148  are placed approximately at 0.018 inches above the blade  180  on the applicator tip  130 . The holes  148  are preferably approximately 0.006 inches in height and oval in shape. The holes  148  are horizontally aligned near the bottom of the applicator tip  130 . The holes  148  create a physical barrier  150  to the fluid which prevents the applicator tip  130  from retaining fluid above the holes  148 . This applicator configuration prevents too much fluid from being retained at the ends of the applicator tip  130  and allows the applicator tip  130  to bend in the vertical and horizontal planes. 
     FIGS. 4-10 show a variety of different applicator tip  130  configurations. FIG. 4 shows an applicator tip  130  with a physical barrier  150  (i.e. the horizontal opening) just above the blade  147 . FIG. 5 shows an applicator tip  130  with serrated teeth. FIG. 6 shows an applicator tip  130  with a physical barrier  150  created by a horizontal row of closely spaced circular openings. FIG. 7 shows an applicator tip  130  with “key hole shape” openings evenly spaced along the bottom of the tip  130 . The “key hole shape” openings are tallest in the middle and become progressively smaller toward the ends. FIG. 8 shows an applicator tip  130  with three horizontal openings just above the bottom. FIG. 9 shows an applicator tip  130  with a row of circular openings just above the bottom of the tip  130 . The circular openings are largest at the middle and become progressively smaller toward the ends. FIG. 10 shows an applicator tip  130  with a “mouse hole” shaped opening. Any of these applicator tips  130  may be disposable. 
     A physical barrier  150  may also be created by making the first portion  140  of the applicator tip  130  rough or texturized. Rough or texturized surfaces have lyophobic characteristics. Thus, if the first portion  140  of the applicator tip  130  has a rough surface, the rough surface prevents the applicator tip  130  from retaining the fluid sample above the barrier  150 . 
     Some common chemical or electrical barriers  150  are created by using an applicator tip  130  with specific lyophobic or lyophilic characteristics or chemically treating the surface. For example, if the first portion  140  of an application tip  130  is made of a lyophobic substance and the second portion  144  is made of a lyophilic substance, only the second portion  144  of the applicator tip  130  will retain fluid. To achieve these results, the first portion  140  should have lyophobic characteristics sufficient to generally prevent it from retaining the fluid sample, and the second portion  144  should have lyophilic characteristics sufficient to generally retain the fluid sample. These results can also be obtained by coating the surface of the applicator tip  130  with chemicals which causes the first portion  140  to posses the necessary lyophobic characteristics and the second portion  144  to possess the necessary lyophilic characteristics. 
     FIG. 11 shows an applicator tip  130  suitable for a chemical or electrical barrier. Some of the techniques for altering the lyophobic or lyophilic characteristics of a portion of the applicator tip  130  are: electrically (corona discharge), chemically (hydrophilic polymer-natural or synthetic) and/or, as stated above, mechanically (abrading or perforating the surface). 
     The preferred technique for creating a chemical barrier  150  is to make the applicator tip  130  out of polyester or nylon, which passes the necessary lyophobic characteristics for the first portion  140 , and create the second portion  144  of the applicator tip  130  by metalizing the polyester surface. 
     The end of the applicator tip  130  is called the blade  147 , as shown in FIG.  3 . The blade  147  is generally a smooth flat edge. In the preferred embodiment, the blade  147  possesses the same lyophilic characteristics as the second portion  144  of the applicator tip  130  so that the fluid sample adheres uniformly to the blade  147  and second portion  144 . 
     In one embodiment, the blade  147  is that portion of the applicator tip  130  which contacts the substrate or plate  110 , and thus, initiates the deposit of the retained fluid onto the substrate. In this embodiment, the retained fluid is released onto the substrate because the contact between the blade  147  and the substrate breaks the surface tension of the retained fluid. In this embodiment, the blade  147  should contact the substrate in a manner to prevent puncturing or damaging the substrate. 
     In an alternative embodiment, the blade  147  may never contact the substrate. For example, the retained fluid may be released when the retained fluid attached to blade  147  contacts the substrate. 
     In addition to the multiple types of applicator tip  130  configurations, there are many different ways to use the applicator tips  130 , individually or in combination. For example, some applicator holders  118  may use a single applicator tip  130 , while others may use a plurality of applicator tips  130 . The single applicator tips  130  may also be combined to resemble a multiple applicator tip assembly  122 . In the preferred embodiment, many applicator tips  130  are permanently connected to form a multiple applicator tip assembly  122 . 
     Moreover, multiple fluid applicators  106  can also be combined to form a cartridge (not shown). Cartridges may be used to connect applicator holders  118  for loading into the applicator rack  540 . Preferably the cartridges are made of plastic and hold three or more applicator holders. Use of the cartridges makes the loading and unloading of the applicators in the rack a quick and simple task. 
     FIG. 12 shows an applicator holder  118  with a guard  162  to protect the applicator tips  130  from damage during manufacture, transport, packaging, etc. The applicator guard  162  is removed or snapped off from the applicator holder  118  at a break point  166  at either end of the applicator holder  118 . The multiple applicator tip assembly  122  is not shown in FIG.  12 . 
     The fluid applicator  106  acquires the fluid sample from a supply tray. As shown in FIG. 13, a supply tray  102  may have a single channel  114  for holding fluid. The channel  114  may be any length. For example, if the channel  114  is built to service a fluid applicator  106  with a single applicator tip  130  the channel will be short. If the supply tray  102  or channel  114  is built to service a multiple applicator tip assembly  122 , the channel  114  will be long enough to accommodate the insertion of all the applicator tips  130  simultaneously. A supply tray  102  is generally made out of plastic or metal. When used for immuno-fixation electrophoresis, the sample stored in the supply tray  102  is usually a biological fluid, such as blood. 
     FIG. 14 shows a preferred supply tray  104 . In this embodiment, the supply tray  104  has three rows  151  of evenly spaced receptacles  155 . The size and spacing of the receptacles  155  depends on the size and spacing of the multiple applicator tip assembly  122 . Preferably, the receptacles  155  are large enough to accommodate one or more applicator tips  130  and deep enough to insert the entire second portion  144  of the applicator tip  130 . The supply tray  104  with rows  151  of individual receptacles  155  is preferred because each row and receptacle  155  may be filled with a different sample fluid. Thus, supply tray  104  is capable of testing more fluids simultaneously than supply tray  102 . For example, the preferred supply tray  104  may contain three rows  151  and each row  151  may include eighteen receptacles  155 . Eighteen receptacles  155  in each row  151  allows each row to contain fluid samples from three different patients. Each patient is allotted six receptacles  155  to allow each patient&#39;s blood to be tested with six different chemicals (for example serum and antisera). 
     FIG. 15 shows a substrate or gel plate  110 . In the preferred embodiment, the gel plate  110  is made out of agarose gel. The substrate  110  should be large enough to receive the fluid samples and be subjected to electrophoresis. For examples of gel plates see U.S. Pat. No. 4,892,639, issued Jan. 9, 1990, entitled “ELECTROPHORESIS PLATE AND METHOD OF MAKING THE SAME”; U.S. Pat. No. 4,975,173, issued Dec. 4, 1990, entitled “ELECTROPHORESIS PLATE AND MAKING OF THE SAME”; and U.S. Pat. No. 5,045,164, issued Sep. 3, 1991; entitled “ELECTROPHORESIS PLATE FOR DIVERTING GENERATED FLUID”, all of which are herein incorporated by reference. 
     In operation, the fluid applicator  106  is moved to a position above the supply tray  102 ,  104  with the application tips aligned above the channel  114 . The applicator tips  130  are then inserted, dunked, or dipped into the receptacles by movement of the applicator holder  118 . During the “dunking” process, the applicator tips  130  retain a quantity of the fluid sample from the channel  114  or receptacle  155 . (The fluid sample is not shown in FIG. 12 or  13 ). Following the “dunking” procedure, the applicator  106  is removed from the channel  114  or receptacle  155  by the applicator holder  118 , moved towards the substrate  110  and lowered in the vertical direction onto the substrate  110  to release the retained fluid. 
     B. Application Station 
     As stated above, an application station is a semiautomatic or automatic device for insuring precise deposit of the fluid sample on the substrate  110 . The application station comprises three main components: a base, applicator guide, and applicator rack. 
     FIG. 16 shows a side view of the base  502  and applicator guide  510  portions of the application station. The base  502  is flat solid structure which can be made of metal, hard plastic, wood, or any sturdy material. The base  502  is usually rectangular with four columns or pillars  506 , but could take almost any shape or contain any number of pillars  506 . In the preferred embodiment, the base is approximately five to seven inches wide, a half inch to two inches high, and five to seven inches long. The pillars  506  protruding from the base  502  connect the base  502  to the applicator guide  510  by fitting within the applicator guide&#39;s feet  514 . The applicator guide&#39;s feet  514  are usually female ends designed to accept the pillars  506 . The base  502  and applicator  510  are shown as two separable components, but these components could be constructed in a variety of different configurations. In other words, the base  502  and applicator guide  510  may be a single unit. 
     FIG. 16 also shows a substrate or gel plate  515  in between the base  502  and applicator guide  510 . The substrate  515  is a flat plate approximately the same size as the base  502  with four holes corresponding to the four pillars  506  protruding from the base  502 . The pillars  506  pass through the substrate  515  to hold the substrate  515  in place during application. In an alternative embodiment, the substrate  515  may be smaller than the base  502  and fit inside an indentation in the base  502 . 
     FIG. 17 shows a top view of the applicator guide  510 . The applicator guide  510  is designed to control the application of biological fluids and other chemicals onto the substrate  515 . The applicator guide  510  controls these applications with the two tracks  524 ,  528  positioned in parallel. The tracks  524 ,  528  are used to control the speed and location in which the fluids, chemicals or substances are deposited onto the substrate  515 . The tracks  524 ,  528  control the location in which a fluid is deposited because they are designed to hold the applicator rack in a first position and a second position. In the first position, the tracks  524 ,  528  hold a fluid applicator  106 , usually mounted in an applicator rack, above the substrate. In the second position, the tracks  524 ,  528  hold the fluid dispenser in a position closer to the substrate. The position closer to the substrate is designed to hold the fluid applicator  106  in a position which will cause the surface tension of the retained fluid to break. Thus, the fluid is released and deposited on the substrate. 
     In the preferred embodiment, the tracks  524 ,  528  control the movement of the fluid applicator  106  with three slides  530 ,  531 ,  532 . The right track  524  has two slides  530 ,  531 , one located near each end, and the left track  528  only has one slide  532  in the middle of the track  528 . In alternative embodiments, the two tracks  524 ,  528  can have the same number of slides in the same location or a variety of other configuration. As stated above, the feet  514  are used to connect the applicator guide  510  to the base  502 . 
     FIG. 18 shows an applicator rack  540  for use with the applicator guide  510 . The rack applicator  540  has a right front post  544 , a right rear post  548 , and a left post  552 . The applicator rack  540  may be attached to the applicator guide  510 . The right front post  544  is designed to align with the applicator guide&#39;s right front slide  530 . The right rear post  548  is designed to align with the applicator guide&#39;s right rear slide  531 , and the left post  552  is designed to align with the applicator guide&#39;s left slide  532 . In the preferred embodiment, each post is aligned with its corresponding slide, and slowly lowered in the vertical direction. The sliding or lowering of the applicator rack  540  from top of the slide to the bottom causes the applicator  106  and applicator tip  130  to move from a position above the substrate  515  to a position in contact with the substrate  515 . When the applicator tip  130  contacts the substrate  515 , it breaks the surface tension between the fluid and the applicator tip  130 . When the surface tension is broken, the fluid carried on the applicator tip  130  is deposited on the substrate  515 . The applicator tip  130  does not necessarily have to contact the substrate  515  to break the surface tension. The applicator guide  510  and applicator rack  540  are designed to minimize the contact and prevent any damage to the substrate  515 . 
     The slides  530 ,  531 ,  532  are also used to improve the control over the speed in which the applicator rack  540  is lowered onto the substrate  515 . The slides  530 ,  531 ,  532  improve the control because they create friction. The friction slows the dissent of the applicator rack  540 . In an alternative embodiment, slides  530 ,  531 ,  532  are not required. The applicator rack  540  may simply be lowered in the vertical direction. In another alternative embodiment, the applicator rack  540  may contact the substrate by moving in a circular path. 
     The applicator rack  540  also has a first set of slots  556  and a second set of slots  560  for holding applicators. Each set of slots contacts a plurality of individual pairs of slots. The slots  556 ,  560  are designed to hold guides  170 ,  174 , like the ones shown in FIG.  1 . These slots  556 ,  560  may differ in size or shape to insure the applicator  106  is properly inserted. In the embodiment shown, the first set of slots  556  is able to hold six applicators  106  simultaneously because it has six individual slots. However, the preferred operation of the system is to leave an empty slot between each applicator  106 , limiting the number of applicators  106  inserted simultaneously to three. 
     The second set of slots  560  includes twelve individual slots. These slots are used to hold chemical dispensers, sera dispensers or other applicators containing chemicals (some of which may improve the visibility of the results achieved from immuno-fixation electrophoresis). 
     In the embodiment shown in FIG. 18, the first set of slots  556  is positioned perpendicular to the second set of slots  560 . This configuration is designed to facilitate use of the application station for different types of electrophoresis, including immuno-fixation electrophoresis. Specifically, the first set of slots  556  are designed to deposit the biological fluid in a “two dimension” line in the X direction. The two dimensional line is achieved by inserting an applicator  106  into the first set of slots  556 , aligning the applicator rack  540  with the slides  530 ,  531 ,  532  in the applicator guide  510 ; lowering the applicator rack  540  along these slides; and depositing the fluid retained on the applicator tip  130  onto the substrate  515 . The deposit is approximately a two dimensional line because of the shape of the tip. 
     Once the fluid is deposited on the substrate  515 , electrophoresis is performed. Electrophoresis causes the molecules deposited in the two dimensional line to migrate in a direction perpendicular (i.e., Y direction) to the two dimensional line created by the deposited fluid. 
     After the electrophoresis is completed, a second applicator  106  is loaded in the second set of slots  560 . Then the second applicator  106  is lowered to dispense chemicals in the Y direction, perpendicular to the originally deposited fluid. Since as a result of the electrophoresis, the molecules migrated in the Y direction, the chemicals are dispensed perpendicularly to the original deposit in the X direction. 
     Also, in the embodiment shown in FIG. 18, the first set of slots  556  and the second set of slots  560  are both aligned in the XY plane. Thus, the applicator rack  540  should not be loaded with applicators  106  in the first set of slots  556  and applicators  106  in the second set of slots  560  at the same time. One of the advantages of this configuration is that it decreases the size of the application station. However, in alternative embodiments, applicators and dispensers can be loaded in the first set of slots and the second set of slots simultaneously. 
     In an alternative embodiment, two sets of slots can be used simultaneously. The first set of slots  556  and a second set of slots  560  are positioned far enough apart along the line of movement of the rack (along the tracks), that the two sets of slots  556 ,  560  do not interfere with each other during use. In this manner, two sets of applicators can be loaded, one in each set of slots, and remain loaded during an entire procedure. The slides are configured in such a manner that the rack would travel along the slides, deposit fluids from the first set of applicators and then be moved so that the fluids on the second set of applicators could be lowered vertically and placed on the substrate (without interference from the first set of applicators). Preferably, the rack for this embodiment is larger in the direction of movement and the slides to support such a larger rack are longer than the rack  540  used in the preferred embodiment. 
     Some of the steps for using the application station or fluid applicator  106  may include: placing the substrate or gel plate  515  into the application station; connecting the application guide  510  to the base  502 ; inserting a first applicator  106  into the applicator rack  540 , usually in the first set of slots  556 ; aligning the pillars  506  of the applicator rack  540  including the first applicator with the applicator guide  510 ; lowering the applicator rack  540 , including the first applicator  106 , onto the substrate  515 ; raising the applicator rack  540 , including the first applicator  106  away from the substrate  515 ; removing the first applicator  106  from the applicator rack  540 ; removing the substrate  515 ; performing electrophoresis on the fluid deposited on the substrate  515 ; reinserting the substrate  515  into the application station; installing a second applicator or dispenser  106  into the applicator rack  540 , usually in the second set of slots  560 ; realigning the applicator rack  540  with the applicator guide  510 ; applying the second applicator  106  using the applicator rack  540  onto the results of the electrophoresis; raising the second applicator  106  using the applicator rack  540 ; removing the substrate  515  treated with the chemical or substance from the second applicator  106 ; and viewing the results. Electrophoresis may also be performed on the substrate while the substrate is on the base beneath the racks. 
     C. Chemical Delivery System 
     In many chemical delivery systems for delivering chemicals or substances to test samples, there are problems associated with the volume of chemicals delivered and the control of the delivery. Specifically, there are problems delivering a known quantity of the chemicals to a precise location on a substrate or sample located on a substrate. Many times, the test sample lanes on the substrate are small, in the range of 1 mm to 5 mm wide. Also, because of factors such as fluid viscosity and adhesion coefficients, the volume of the chemical being delivered may prematurely or spontaneously unload and drip prior to delivery. Delivery applicators in the prior art have these and related problems. 
     FIG. 19 shows a delivery system applicator  600 . The delivery system applicator  600  includes a delivery system applicator holder  604  with a left guide  608 , a right guide  612 , and a reservoir  616 . 
     The delivery system holder  604  may be constructed similar to the sample fluid applicator holder  118 . The delivery system applicator holder  604  can be constructed of a plastic, such as styrene, or other materials known in the art. The right and left guides  608 ,  612  may be made identical and symmetrical or, may be shaped differently so that the holder  604  can only be aligned or placed in the applicator rack  540  in one direction or position. The left and right guides  608 ,  6122  may be constructed similar to the guides in the sample fluid applicator  106  described above. 
     The reservoir  616  is preferably an elongated well or tunnel-shaped reservoir. The reservoir  616  has an opening preferably located at the bottom and away from the delivery applicator holder  604 . The reservoir  616  may be made from a variety of materials including those from which the applicator holders  604 ,  118 , are constructed. The reservoir  616  is connected to the holder  604 . A variety of methods may be used for connecting the reservoir to the holder, including a snap fit plastic connection, adhesives (such as glue or tape), screws or fasteners, heat weld, ultrasonic sealing, etc. Many of the methods described above for connecting the multiple applicator tip assembly  122  to the applicator holder  118  can also be used to connect the reservoir  616  to the delivery system holder  604 . 
     Preferably, the reservoir  616  is shaped or formed to hold a gel or “gel-like” substance. Various configurations are possible for the reservoir, including with lips or ledges around the edge of the reservoir and other structures within the reservoir  616  to assist in keeping the gel held within the reservoir  616 . 
     A variety of fluid retaining substances (such as gel forming substances) may be used in the reservoir  616  of the delivery system  600 . Some examples are polymers, gels, agarose, polysaccharide, carrageenan, and other fluid retaining substances that have the consistency necessary to be effectively used in the reservoir  616 . 
     A variety of chemicals or fluids may be delivered using the disclosed delivery system  600 . For example, serum protein and antiserums may be delivered using the delivery system  600 . The serum proteins and antiserums are held by the fluid retaining substances in the reservoir  616 . 
     In operation, it is preferred that a mixture of the chemical or fluid to be delivered and the fluid retaining substance is made and poured, cast or placed in the reservoir  616  where it congeals and is held or adhered to the reservoir  616 . Although various methods for the reservoir  616  to hold the fluid retaining substance and chemical or fluid are possible, it is preferred that the chemical and fluid retaining substance are cast (together) into the reservoir  616  where the cast itself holds the fluid retaining substance and chemical in place. Other methods may be used for holding the fluid retaining substance and chemical in the reservoir  616 : including shaping the reservoir  616  so as to hold the fluid retaining substance (and chemical) such as with lips or ledges running along the perimeter of the reservoir  616 , adhesives, or other methods. Generally, the delivery system  600  is loaded with fluid retaining substance and fluid or chemical when it is in an inverted or upside down position. Loading the fluid retaining substance and fluid in this manner allows it to gel in place within the reservoir before the forces of gravity begin to pull on it and pull it away from the reservoir  616 . This pre-loading of the chemical or fluid eliminates the need for a dunking step. 
     In use, the applicator  600  is preferably held in an upright position by semiautomatic or automatic chemical delivering device. Such a device, several of which are herein disclosed, would use the guides  608 ,  612  to hold the delivery system applicator  600  in place during the delivery process. The device brings the delivery system applicator  600  towards the substrate  110 ,  515  and creates a contact between the substrate and the delivered chemical and/or fluid retaining substance in the reservoir  616 . When the “gel-like” substance in the reservoir makes contact with the substrate, a controlled volume of chemical or fluid is delivered to the substrate. Using this delivery method the delivered chemical or fluid can also be placed in a precise location on the substrate. 
     With regard to using the following apparatuses and methods in an automated immuno-fixation electrophoresis process using six chemical sample treatments, the following information applies. For general information on the automated immuno-fixation electrophoresis process, see U.S. Pat. No. 5,137,614 entitled “IMMUNOFIXATION ELECTROPHORESIS CONTROL SYSTEM”, issued on Aug. 11, 1992, hereby incorporated by reference. 
     In the preferred embodiment, the six chemical treatment tests are performed as follows. 
     The first test is an analysis of total serum protein (SP) and the remaining five tests are each used in the detection of a different protein. This is conventional in an IFE process. 
     The six tests are usually a total serum protein test [designated SP] followed by tests for the presence or absence of the monoclonal immunoglobulins IgG, IgA, IgM, Kappa and Lambda [designated G, A, M, K and L, respectively]. 
     For the serum protein test, it is preferred that the fluid retaining substance be carrageenan. More specifically, the preferred serum protein fixative is 10% acetic acid, 5% sulfosalicylic acid and 1% tannic acid. In the preferred method, this serum protein fixative (10% acetic acid, 5% sulfosalicylic acid, 1% tannic acid) is mixed with 2% carrageenan and then, the entire solution is diluted by one half. Therefore, in the final solution for the reservoir  616 , approximately 1% carrageenan is preferred. 
     The remaining five tests (tests number 2-6), use antisera. Each antisera [tests 2-6, G, A, M, K, and L] is mixed with a 2% low melting point agarose so that the final concentration of the solution is 7.5 milligrams per milliliter [mg/ml]. 
     While carrageenan, a polysaccharide is preferred for the serum protein test (as the fluid retaining substance or polymer), it is preferred that the antisera tests use agarose as the fluid retaining substance or polymer with each respective antisera. 
     III. An Automatic System 
     The methods and techniques of the present invention can also be performed automatically. FIG. 20 shows an example of an automatic immuno-fixation electrophoresis system  200  which automates the methods and techniques. The system has seven stations. The seven stations are: sample applicator station  301 ; electrophoresis station  302 ; antisera or chemical delivery station  303 ; first drying fan station  305 ; wash station  304 ; second drying fan station  306 ; and stain/destain station  307 . 
     The system is initiated when a carrier is inserted in the entrance  300 . The carrier is a metal or plastic sheet or tray which is designed to move between the stations. The mechanics which move the carrier can be configured a variety of ways, including a conveyor or other motorized delivery system  309 . The timing of the movements is controlled with a preprogrammed microprocessor. For example, when a carrier is inserted in the entrance and the system is initiated, the preprogrammed microprocessor instructs the motorized delivery system  309  to move the carrier into the applicator station  301 . 
     The applicator station  301  receives the carrier, selects a fluid sample with a fluid applicator from a sample tray; deposits the sample on the substrate; and forwards the carrier to the electrophoresis station  302 . Specifically, at the instruction of a preprogrammed microprocessor, a motorized device lowers the fluid applicator to retain the sample, moves the fluid applicator to a position above the substrate, lowers the fluid applicator to deposit the retained fluid on the substrate, and returns the fluid applicator to its home position. 
     Then the carrier is moved to the electrophoresis station  302 . At the electrophoresis station  302 , the fluid sample is separated into its component molecules with electrophoretic techniques. 
     Next, the carrier is moved to the antisera station  303 . At the antisera station  303 , a substance or chemical delivery applicator is used to automatically apply a substance or chemical to the separated molecules. Generally, these substances are designed to enhance the visibility of certain molecular structures. Similar to the sample applicator station  301 , the chemical delivery applicator is connected to a motorized apparatus which automatically moves the applicator through the necessary steps to apply the substance. Preferably, the chemicals are “pre-loaded” onto the chemical delivery applicator and therefore, no dunking step is necessary. 
     After the substance or chemicals are applied, the carrier may be moved to the first wash station  304  and the first drying fan station  305 . After the first drying station  305 , the carrier may be moved to the stain/destain station  307 , followed by the second drying station  306 , and exit  308 . 
     The foregoing description of the present invention has been presented for purposes of illustration and description. The description is not intended to limit the invention to the forms described. Variations and modifications commensurate with the above teachings, and within the skill and knowledge of the relevant art, are part of the scope of the present invention.