Abstract:
In one arrangement, a cartridge includes a cartridge body defining a holding compartment, first and second fractioning compartments, and a number of flow channels formed within the cartridge body. A predetermined quantity of fluid can be held in the holding compartment when the cartridge body is held in a first orientation, and can be poured from the holding compartment to the first fractioning compartment by rotating the cartridge body about a predefined rotation axis to a second orientation, spilling the fluid from the holding compartment to the first fractioning compartment through one of the flow channels. The first fractioning compartment is such that when the cartridge body is in the second orientation, not all of the fluid can be contained in the first fractioning compartment, and fluid that overflows the first fractioning compartment flows through a second flow channel to the second fractioning compartment.

Description:
[0001]    This application claims the benefit of U.S. Provisional Patent Application No. 62/132,984, filed Mar. 13, 2015, and titled “Assay Cartridge”, the entire disclosure of which is hereby incorporated by reference herein for all purposes. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    A wide variety of systems and methods exist for performing biochemical analysis, for example for medical testing. A common technique is to load analytes and reagents into a microfluidic “chip” that has fluid flow channels and other structures formed in it using photolithography techniques. Such a chip may include pumps, reservoirs, valves, mixing structures, and other features useful in the performance of a certain tests. 
         [0003]    Typically, such a chip is controlled by an external controller, through application and release of fluid pressure at key points in the chip. For example, a valve may be formed by crossing a fluid flow channel in a soft medium with a dead-end cross channel. By pressurizing the cross channel, the fluid flow channel can be pinched off, and by releasing the pressure in the cross channel, the fluid flow channel is allowed to re-open. A peristaltic pump may be formed by placing three or more such valves close together crossing a fluid flow channel in a soft medium. By sequentially pressurizing and depressurizing the valves channels to pinch off and re-open adjacent locations in the fluid flow channel, fluid can be caused to flow in the fluid flow channel. 
         [0004]    Because of the need for complex external pressure control, such microfluidic chips are not convenient for use in routine medical testing, especially in remote locations. 
       BRIEF SUMMARY OF THE INVENTION 
       [0005]    According to one aspect, a cartridge for fluid manipulation comprises a cartridge body defining a holding compartment and first and second fractioning compartments formed within the cartridge body. The cartridge body also defines a number of flow channels formed within the cartridge body. The compartments and flow channels are arranged such that a predetermined quantity of fluid can be held in the holding compartment when the cartridge body is held in a first orientation, and can be poured from the holding compartment to the first fractioning compartment by rotating the cartridge body about a predefined rotation axis to a second orientation, to spill the fluid from the holding compartment to the first fractioning compartment through a first one of the flow channels. The first fractioning compartment is of a shape, size, and position such that when the cartridge body is in the second orientation, not all of the fluid can be contained in the first fractioning compartment. The first fractioning compartment is connected to the second fractioning compartment by a second one of the flow channels, such that any of the fluid that overflows the first fractioning compartment when the cartridge body is in the second orientation flows through the second flow channel to the second fractioning compartment. 
         [0006]    In some embodiments, the first and second fractioning compartments are shaped, sized, and positioned such that the predetermined quantity of fluid can be held in substantially equal quantities in the first and second fractioning compartments when the cartridge body is held in the second orientation. In some embodiments, the cartridge body defines a third fractioning compartment; the first and second fractioning compartments are shaped, sized, and positioned such that the predetermined quantity of fluid cannot be contained within the first and second fractioning compartments when the cartridge body is in the second orientation; and the second fractioning compartment is connected by a third one of the flow channels to the third fractioning compartment, such that any of the fluid that overflows the second fractioning compartment when the cartridge body in the second orientation flows through the third flow channel to the third fractioning compartment. In some embodiments, the first, second, and third fractioning compartments are shaped, sized, and positioned such that the predetermined quantity of fluid can be held in substantially equal quantities in the first, second, and third fractioning compartments when the cartridge body is held in the second orientation. In some embodiments, the cartridge further comprises two analysis areas, one analysis area respectively for each fractioning compartment, wherein the analysis areas are connected directly or indirectly to the respective fractioning compartments by respective ones of the flow channels, and the analysis areas are positioned such that fluid held in the fractioning compartments when the cartridge body is in the second orientation can be delivered to the respective analysis areas by one or more subsequent rotations of the cartridge body about the rotation axis, to spill fluid from the fractioning compartments and into the respective connections to the analysis areas. In some embodiments, the cartridge body further defines two mixing compartments, one mixing compartment respectively for each fractioning compartment, and wherein the fluid spilled from the fractioning compartments passes through the respective mixing compartments before reaching the respective analysis areas. In some embodiments, each of the mixing compartments stores a quantity of a reagent positioned to mix with the fluid spilled from the respective fractioning compartment before the fluid flows to the respective analysis area. In some embodiments, the fluid is a first fluid; the cartridge body further defines a second set of compartments and flow channels for manipulating a second fluid in sequence through the second set of compartments in reaction to the rotations of the cartridge about the rotation axis; the cartridge body further defines a second set of outlet channels respectively connecting the last of the second set of compartments with the analysis areas; and the second set of compartments and flow channels and the outlet channels are shaped, sized, and positioned such that the second fluid reaches the analysis areas later than the first fluid when the cartridge is rotated in such a way as to deliver the first fluid to the analysis areas. In some embodiments, the lengths of the outlet channels are selected to ensure that the second fluid will reach the analysis areas later than the first fluid. 
         [0007]    According to another aspect, a cartridge for fluid manipulation comprises a cartridge body. The cartridge body defines a first set of compartments and flow channels for manipulating a first fluid. The compartments and channels in the first set are sized, shaped, and positioned such that a sequence of rotations of the cartridge body about a predefined rotation axis will cause a quantity of the first fluid to sequentially pass through all of the compartments in the first set via the first set of flow channels to reach an outlet of the first set of compartments and flow channels. The cartridge body defines a second set of compartments and flow channels for manipulating a second fluid. The compartments and channels in the second set are sized, shaped, and positioned such that the same sequence of rotations of the cartridge body about the predefined rotation axis will cause a quantity of the second fluid to sequentially pass through all of the compartments in the second set via the second set of flow channels to reach an outlet of the second set of compartments and flow channels. In some embodiments, the outlets of the first and second sets of compartments and flow channels are joined at a junction, and the first and second sets of compartments and flow channels are shaped, sized, and positioned such that the second fluid reaches the junction at a different time than the first fluid in response to the sequence of rotations. In some embodiments, the cartridge further comprises: a reservoir holding a sample fluid and a washing buffer fluid in separate compartments of the reservoir, the reservoir including two openings sealed by puncturable sealing covers; two hollow piercing elements positioned on the cartridge body such that the two piercing elements pierce the puncturable sealing covers of the reservoir when the reservoir is joined to the cartridge body, enabling the sample fluid and the washing buffer fluid to pass through the two hollow piercing elements and to pass respectively to the first set of compartments and flow channels and the second set of compartments and flow channels, the sample fluid being the first fluid and the washing buffer fluid being the second fluid; and an analysis area at the junction; wherein at least some of the compartments in the first set of compartments store quantities of reagents for mixing with the sample fluid as the sample fluid traverses the first set of compartments and flow channels, the reagents usable to conduct an assay of the sample fluid; and wherein the analysis area enables reading of a result of the assay. In some embodiments, the analysis area comprises an absorbent medium through which the sample fluid and the washing buffer fluid can sequentially transport by capillary action. 
         [0008]    According to another aspect, a testing system comprises a cartridge for fluid manipulation as in claim  1 , a motorized mechanism for producing a rotary motion of cartridge about a rotational axis, and a controller having a processor and memory. The controller is coupled to the motorized mechanism and programmed to cause the motorized mechanism to produce a predetermined series of rotations of cartridge in accordance with a predetermined assay. 
         [0009]    According to another aspect, a method of conducting an assay comprises providing a cartridge having a cartridge body defining a holding compartment and first and second fractioning compartments formed within the cartridge body. The cartridge body also defines a number of flow channels formed within the cartridge body. The method further comprises placing a quantity of fluid in the holding compartment and holding the cartridge body in a first orientation, and rotating the cartridge about a predefined rotation axis to a second orientation to pour at least some of the fluid from the holding compartment through a first one of the flow channels to the first fractioning compartment. The first fractioning compartment is of a shape, size, and position such that when the cartridge body is in the second orientation, not all of the fluid can be contained in the first fractioning compartment. The first fractioning compartment is connected to the second fractioning compartment by a second one of the flow channels, such that any of the fluid that overflows the first fractioning compartment when the cartridge body is in the second orientation flows through the second flow channel to the second fractioning compartment. In some embodiments, the method further comprises rotating the cartridge about the rotation axis to one or more subsequent orientations, causing the fluid to spill from the two fractioning compartments to reach respective analysis areas in the cartridge. In some embodiments, the method further comprises pausing between successive rotations of the cartridge to allow an analyte in the fluid to react with a reagent previously stored in one of the compartments. In some embodiments, the rotation axis is a first rotation axis, the method further comprising rotating the cartridge about a second rotation axis different from the first. The method may further comprise depositing an analyte in the quantity of fluid. In some embodiments, depositing the analyte in the quantity of fluid comprises injecting the analyte through a puncturable seal. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0010]      FIG. 1  illustrates an oblique exploded view of a cartridge for fluid manipulation, in accordance with embodiments of the invention. 
           [0011]      FIG. 2  illustrates a pre-loaded reservoir, in accordance with embodiments of the invention. 
           [0012]      FIG. 3  illustrates a sample injection into the reservoir of  FIG. 2 , in accordance with embodiments of the invention. 
           [0013]      FIG. 4  illustrates the reservoir of  FIG. 2  joined to a cartridge body, in accordance with embodiments of the invention. 
           [0014]      FIG. 5  illustrates a sample fluid and a washing buffer fluid in compartments of an assay cartridge, in accordance with embodiments of the invention. 
           [0015]      FIGS. 6A and 6B  illustrate a rotational motion of the cartridge of  FIG. 1  and a resulting fluid motion, in accordance with embodiments of the invention. 
           [0016]      FIG. 7  illustrates another rotational motion of the cartridge of  FIG. 1  and resulting fluid motion, in accordance with embodiments of the invention. 
           [0017]      FIG. 8  illustrates another rotational motion of the cartridge of  FIG. 1  and resulting fluid motion, in accordance with embodiments of the invention. 
           [0018]      FIG. 9  illustrates another rotational motion of the cartridge of  FIG. 1  and resulting fluid motion, in accordance with embodiments of the invention. 
           [0019]      FIG. 10  illustrates a completed fluid flow, in accordance with embodiments of the invention. 
           [0020]      FIG. 11  illustrates an additional degree of freedom of rotation of the cartridge of  FIG. 1 , in accordance with embodiments of the invention. 
           [0021]      FIG. 12  illustrates a cartridge for fluid manipulation, in accordance with other embodiments of the invention. 
           [0022]      FIG. 13  illustrates a rotational motion of the cartridge of  FIG. 12  and a resulting fluid motion, in accordance with embodiments of the invention. 
           [0023]      FIG. 14  illustrates a schematic view of a system for performing an assay using a cartridge such as the cartridge of  FIG. 1  or the cartridge of  FIG. 12 , in accordance with embodiments of the invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0024]      FIG. 1  illustrates an oblique exploded view of a cartridge  100  for fluid manipulation, in accordance with embodiments of the invention. Cartridge  100  includes a cartridge body  101 , in which are formed a number of compartments  102  and fluid flow channels  103  connecting the compartments  102  and other structures. Compartments  102  and fluid flow channels  103  are shaped, sized, and positioned to accomplish certain fluid manipulations when cartridge  100  is rotated about axis  104 , as is explained in more detail below. Cartridge body  101  may be machined, molded, printed, or otherwise fabricated from any suitable material, for example a biocompatible polymer. 
         [0025]    Cartridge  100  further includes a reservoir  105  having multiple isolated compartments  106 . Compartments  106  may be used to hold fluids to be manipulated in cartridge  100 . For example, one compartment may be loaded with a sample fluid for carrying an analyte, and another of compartments  106  may be loaded with a washing buffer fluid. Puncturable seals  107   a,    107   b  may be placed over openings in reservoir  105 , to retain the pre-loaded fluids. For example, cover  109  and puncturable seal  107   a  may be placed on reservoir  105 , and the fluids loaded through the remaining openings in reservoir  105  (shown at the bottom of reservoir  105  in  FIG. 1 ). Puncturable seals  107   b  may then be put in place to seal reservoir  105  in preparation for a particular test. Cover  108  is also placed over cartridge body  101 , to seal the various structures of cartridge body  101 . 
         [0026]    A specimen containing an analyte may be introduced to the sample fluid using a sample injector  110 . For example, sample injector may include a sharp hollow needle or similar structure  111  for puncturing puncturable seal  107   a  and carrying the analyte to reservoir  105 . In some embodiments, the specimen may be a human blood sample and cartridge  100  is configured to perform an assay for glycated hemoglobin (HbA1c), useful in diagnosing and monitoring diabetes and capable of detecting the presence of variant forms of hemoglobin that are relevant to HbA1c measurements. It will be recognized that the invention may be embodied in many other ways as well. Example cartridge  100  also includes analysis areas  112 , as will be explained in more detail below. Cover  108  may include viewing windows  114  for viewing analysis areas  112  from outside cartridge  100 . In other embodiments, cover  108  may be made of a transparent material such as glass or a transparent polymer, to allow viewing of analysis areas  112 . 
         [0027]    Example cartridge body  101  also includes two hollow piercing elements  113  positioned to pierce puncturable seals  107   b  when reservoir  105  is mated to cartridge body  101 , and to carry the respective fluids from reservoir compartments  106  to cartridge body compartments  102 . 
         [0028]      FIGS. 2-10  illustrate the use and operation of cartridge  100 , to perform one example kind of assay. In these figures, covers  108  and  109  have been removed to show the internal workings of cartridge  100 . 
         [0029]    In  FIG. 2 , respective compartments  106  of reservoir  105  have been pre-loaded with a sample fluid  201  and a washing buffer fluid  202 . Puncturable seals  107   a  and  107   b  are in place to seal reservoir  105 . The types and quantities of fluids  201  and  202  may be selected in accordance with the particular test being conducted. 
         [0030]    In  FIG. 3 , sample injector  110  has pierced puncturable seal  107   a,  and provides an analyte  301  to mix with sample fluid  201 . 
         [0031]    As is shown in  FIG. 4 , once the analyte has mixed with sample fluid  201 , reservoir  105  is joined with cartridge body  101 , such that hollow piercing elements  113  puncture puncturable seals  107   b  and allow the sample fluid  201  and washing buffer fluid  202  to flow into respective compartments  401  and  402  of cartridge body  101 . As is also visible in  FIG. 4 , at least some compartments in cartridge body  101  may be pre-loaded with reagents  403 . Reagents  403  may be, for example, pellets of lyophilized reagent that will be reconstituted upon contact with sample fluid  201 . In other embodiments, appropriate reagents may be placed in the various compartments of cartridge body  101  in a liquid form and then dried, so that the reagents are reconstituted upon contact with liquid flowing into the various compartments. The various reagents may include, for example, pepsin to process the sample, a neutralizer to adjust pH, microparticles coated with antibody for detecting glycated hemoglobin (HbA1c) and total hemoglobin (tHb), microparticles for detecting hemoglobin variants S, C, E, and D (SCED), or other kinds of reagents, depending on the intended use of the cartridge. In the case where cartridge  100  is used in an HbA1c assay, the reagent in compartment  401  may be pepsin. 
         [0032]    While reservoir  105  is shown as being joined to cartridge body  101  by a simple linear motion, it will be recognize that many other joining motions and techniques may be used. For example, reservoir  105  may undergo a rotational or sliding motion to connect with cartridge body  101  and to reach hollow piercing elements  113 . 
         [0033]      FIG. 5  shows the state of cartridge  100  after sample fluid  201  and washing buffer fluid  202  have drained into cartridge compartments  401  and  402 . During the steps of  FIGS. 2-5 , cartridge  100  has been held in a first, vertical orientation. Cartridge  100  may be held in this first orientation for a period of time, if desired, to allow sample fluid  201  to react with reagent  403  in compartment  401 , depending on the particular test being run. 
         [0034]    In some embodiments, one or more compartments may include structures that can aid in mixing of fluids and reagents. For example, as shown in  FIG. 5 , each of reagent pellets  403  may be housed in a sharp-edged pocket  404 . Once sample fluid  201  has reached compartment  401  and is mixing with the reagent pellet, cartridge  100  may be rotated back and forth around axis  104  to agitate sample fluid  201 . The sharp edges of the pocket may promote mixing of sample fluid  201  with reagent pellet  403 . 
         [0035]    In  FIG. 6A , cartridge  100  is being rotated about axis  104 . The rotation may be accomplished, for example, by a rotary mechanism (not shown) configured to perform a prescribed sequence of rotations in accordance with a specific tests. Preferably, the mechanism is programmable for use with different cartridges for performing different tests, and can perform any required sequence of rotations of cartridge  100 . 
         [0036]    In  FIG. 6A , sample fluid  201  is spilling into cartridge compartment  601 , and washing buffer fluid  202  is spilling into cartridge compartment  602 . In  FIG. 6B , cartridge  100  has reached an orientation in which the fluids  201  and  202  are held in their respective compartments  601  and  602 . Cartridge  100  may be held in this orientation to allow sample fluid  201  to react with reagent  403  in compartment  601 , if desired. In the case where cartridge  100  is used in an HbA1c assay, the reagent in compartment  601  may be a neutralizer. 
         [0037]    In  FIG. 7 , cartridge  100  has again been rotated about axis  104 , but in the opposite direction from before, spilling fluids  201  and  202  from compartments  601  and  602 . Washing buffer fluid  202  has spilled into compartment  702 . (The intermediate flow is not shown.) In addition, sample fluid  201  has spilled from compartment  601  into a first fractioning compartment  701   a.  However, first fractioning compartment  701   a  is smaller in volume than the volume of sample fluid  201 , and part of sample fluid  201  has overflowed first fractioning compartment  701   a  and flowed to second fractioning compartment  701   b.  Thus, sample fluid  201  has been “fractioned” into two smaller volumes. 
         [0038]    In  FIG. 8 , cartridge  100  has been further rotated to spill sample fluid  201  from fractioning compartments  701   a  and  701   b  into additional compartments  801   a  and  801   b.  There, sample fluid  201  may react with stored reagents  403  if desired. Washing buffer fluid  202  has similarly spilled from compartment  702  into compartment  802 . In the case where cartridge  100  is used in an HbA1c assay, the reagent in compartments  801   a  and  801   b  may include A1c and tHb microparticles in one of compartments  801   a  and  801   b,  and SCED microparticles in the other compartment. 
         [0039]    In  FIG. 9 , cartridge  100  has again been rotated about axis  104 , so that the two portions of sample fluid  201  spill from compartments  801   a  and  801   b,  and into channels  901   a  and  901   b,  which conduct sample fluid  201  to analysis areas  112 . Each analysis area  112  may include, for example, an absorbent medium impregnated with proteins to which the antibodies from sample fluid  201  may attach. The absorbent medium may comprise nitrocellulose or another kind of absorbent medium. Sample fluid  201  may transport across the absorbent medium by capillary wicking action. Different areas of the absorbent medium may be impregnated with different proteins to which different antibodies may attach. 
         [0040]    In the meantime, washing buffer fluid  202  has spilled from compartment  802  and into channels  902 , to be carried by capillary action toward analysis areas  112  as well. However, because channels  902  are longer than channels  901   a  and  901   b,  washing buffer fluid  202  arrives at analysis areas  112  later than does sample fluid  201 . By the time washing buffer fluid  202  arrives at analysis areas  112 , sample fluid  201  may have already substantially soaked into the absorbent medium of analysis areas  112 , and washing buffer fluid  202  may carry sample fluid  201  further across analysis areas  112 . Washing buffer fluid  202  may serve to carry away antibodies not bound to any of the proteins present in analysis areas  112 , removing stray antibodies that could otherwise interfere with interpretation of the test result. Washing buffer fluid  202  and other fluid components it carries may be exhausted into a collection area (not shown) within cartridge  100 . 
         [0041]      FIG. 10  illustrates the completion of the flows of sample fluid  201  and washing buffer fluid  202 . To read the result of the test, analysis areas  112  may be illuminated in order to stimulate fluorescence of the fluorphores tagged to the antibodies adhering to the various areas of analysis areas  112 . The wavelengths and intensity of light emanating from analysis areas  112  may be measured and interpreted to provide a test result. 
         [0042]    It will be recognized that many, many variations from this example are possible within the scope of the appended claims. The number, size, and arrangement of compartments present in a particular cartridge may be varied according to the intended use of the cartridge. Only one set of compartments and channels may be provided, or more than two sets of compartments and channels may be provided, for manipulating more than two fluids. Different kinds of analysis areas may be provided, according to the intended use of the cartridge. And while only two fractioning compartments are shown in the above example, it will be recognized that three or more fractioning compartments may be provided, so that a fluid sample can be divided in to any workable number of smaller quantities for performing different tests or for other purposes. 
         [0043]    In some embodiments, and additional axis of rotation of cartridge  100  may be provided. For example, the rotation mechanism that provides rotations of cartridge  100  about axis  104  may also include a second rotational degree of freedom as shown in  FIG. 11 , in which cartridge  100  can also rotate about axis  1101 , orthogonal to axis  104 . Motions in this additional degree of freedom may be used for additional agitation of fluids and reactants, to control the flow of fluids within cartridge  100 , or for other purposes. For example, cartridge  100  may tilted “back” (in the direction shown in  FIG. 11 ) to retain some fluid in compartments  801   a,    801   b,  and  802  rather than letting all of the fluid flow to shallow channels  901   a,    901   b,  and  902 . In another example, a controlled tilting motion in the “forward” direction (opposite the tilt shown in  FIG. 11 ) may be used to slowly meter fluid into channels  901   a,    901   b,  and  902  from compartments  801   a,    801   b,  and  802 . 
         [0044]    An assay cartridge such as cartridge  100  may be particularly useful in a point-of-care or field hospital environment, because the motions required for completing an assay are simple and easily accomplished. For example, especially when cover  108  is transparent, the rotational motions and test sequence described in conjunction with  FIGS. 2-10  may be accomplished without any additional mechanism or machinery at all. A user may simply move cartridge  100  by hand, observing the fluid flow from one compartment to the next, and holding cartridge  100  in each orientation for a prescribed amount of time. If analysis areas  112  provide a visual result, the test result may be read directly from analysis areas  112  through cover  108 , possibly with the aid of a light source to stimulate fluorescence. Cartridge  100  may be made of low-cost materials, for example molded polymers or the like, and thus may be disposable. 
         [0045]      FIG. 12  illustrates an assay cartridge  1200  in accordance with another embodiment. Cartridge  1200  differs from cartridge  100  in its technique of sample loading, and in that it includes only one set of compartments and channels for manipulating a single fluid, rather than two sets for manipulating two fluids as in cartridge  100 . Example cartridge  1200  is otherwise similar to cartridge  100 , and is therefore shown only in a face-on view. 
         [0046]    In cartridge  1200 , a sample fluid  1201  may be pre-loaded in a compartment  1202  of cartridge  1200  itself, rather than in a separate reservoir. Compartment  1202  may be lined with puncturable seals  1203 . An analyte  1204  may be introduced directly into compartment  1205 , for example using a sample injector or needle  1206 . 
         [0047]    As shown in  FIG. 13 , cartridge  1200  may then be rotated about axis  1301  to allow sample fluid  1201  to spill into compartment  1205 , for example though a slot in sample injector  1206 , or through the opening in lower puncturable seal  1203  after sample injector  1206  has been partially or completely withdrawn. Once compartment  1205  has received sample fluid  1201 , sample fluid  1201  may react with a reagent such as reagent  1302 , and cartridge  1200  may be subjected to a series of rotations similar to the steps of  FIGS. 6A-10 , to bring sample fluid  1201  (with analyte  1204 ) to analysis areas  1303 . 
         [0048]      FIG. 14  illustrates a schematic view of a system  1400  for performing an assay using a cartridge such as cartridge  100 , in accordance with embodiments of the invention. In example system  1400 , cartridge  100  is slid into a holder  1401 . Cartridge  100  may be retained in holder  1401  by friction, or by a latching mechanism (not shown) of any suitable design. Holder  1401  is in turn rotationally coupled to a yoke  1402 . A motor  1403  may be provided for automatically turning holder (and cartridge  100 ) within yoke  1402  about axis  1404 . Yoke  1402  is rotationally coupled to a base  1405 . A second motor  1406  may be provided for automatically turning yoke (and holder  1401  and cartridge  100 ) about axis  1407 . Axes  1404  and  1407  may be orthogonal to each other, although this is not a requirement. A controller  1408  is coupled to motors  1403  and  1406 , and is programmed to cause cartridge  100  to be subjected to a sequence of rotational motions about either or both of axes  1404  and  1407 , to accomplish a particular test or assay using cartridge  100 . Controller  1408  may include selectable programs for performing a number of different tests and assays, using a number of different cartridge types. Any or all parts of the mechanism of  FIG. 14  may be embedded in a testing instrument. 
         [0049]    In the claims appended hereto, the term “a” or “an” is intended to mean “one or more.” The term “comprise” and variations thereof such as “comprises” and “ comprising,” when preceding the recitation of a step or an element, are intended to mean that the addition of further steps or elements is optional and not excluded. 
         [0050]    It is to be understood that any workable combination of the elements and features disclosed herein is also considered to be disclosed. 
         [0051]    The invention has now been described in detail for the purposes of clarity and understanding. However, those skilled in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims.