WO2002014556A2

WO2002014556A2 - Rotary multiplexed microarrayer and method for production of microarrays

Info

Publication number: WO2002014556A2
Application number: PCT/US2001/025356
Authority: WO
Inventors: Brian B. Haab
Original assignee: Van Andel Research Institute
Priority date: 2000-08-14
Filing date: 2001-08-13
Publication date: 2002-02-21
Also published as: WO2002014556B1; AU2001281265A1; WO2002014556A3

Abstract

An apparatus (110) for printing microarrays of at least one substance on at least one slide (158) is provided comprising a base (114) and a platter (112) mounted to the base (114) for rotational movement about a z-axis. At least one arm (26) is mounted to the base (114) above the platter (112) for radial movement with respect to the z-axis of the platter (112). A print head (134) is mounted to each of the at least one arm (126) for reciprocating movement along the z-axis and, the print head (134) having at least one substance-dispensing device (140) thereon. The at least one substance can be printed onto the at least one slide (158) in the form of a microarray by the incremental rotational movement of the platter (112) about the z-axis, the radial movement of the at least one arm (126), and by the z-axis movement of the print head (134). A method of printing microarrays is also provided.

Description

ROTARY MULTIPLEXED MICRO ARRAYER AND METHOD FOR PRODUCTION OF MICROARRAYS

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No.

60/225,129, filed on August 14, 2000.

BACKGROUND OF THE INVENTION Field of the Invention

The invention relates to microarrays. In one of its aspects, the invention relates to an apparatus for depositing closely-aligned microarrays of material onto an array of slides for laboratory use. In another of its aspects, the invention relates to a microarrayer apparatus for efficiently and quickly depositing the microarrays onto slides located on a rotary platter. In another of its aspects, the invention relates to a method for efficently depositing closely-aligned microarrays of material onto an array of slides for laboratory use.

Description of the Related Art

Microarrayers are used in laboratories for depositing microarrays made up of multiple samples (even tens of thousands) of material, such as DNA and other biomolecules) onto a glass slide for analysis. Microarrays are very useful in genetic research and have been used to provide highly parallel concentration information on thousands of nucleic acid fragments in a miniaturized, low- volume format. The ability to quantify multiple DNA or RNA fragments simultaneously has many applications, such as basic biological research, molecular classification of disease subtypes, identification of therapeutic markers and targets, and profiling of response to toxins and pharmaceuticals.

In one mode of use, mRNA from a population of cells is fluorescently labeled, mixed with a differentially labeled reference pool of mRNA, and hybridized to a microarray. Detection of the binding to the array by fluorescence scanning reveals the transcriptional profile of the cells. The mRNA expression of nearly every gene in yeast can be measured using cDNA arrays to examine transcriptional changes during diauxic shifts and to identify cell cycle regulated genes. Expression profiles of cultured human cells can be measured to gain insight into the response of fibroblasts to serum stimulation, the response of various cell lines to drugs, the effect of HTV infection on CD4+ T cells, and the effects of genetic changes. mRNA taken from human tissue has been examined to identify subtypes of diffuse large B-cell lymphoma, to establish a molecular classification of two types of acute leukemia, to identify multiple sclerosis associated genes, and to classify breast cancer samples based on gene expression patterns. DNA microarrays have had other applications in addition to mRNA expression analysis, including the examination of genomic copy number changes and the subcellular location of RNA transcripts. The microarrayers typically employed to create these microarrays often include a moveable platter that is configured to align many glass slides, often in excess of one hundred slides, so that a deposit mechanism can deposit material onto the slides. The deposit mechanism typically comprises a robotic arm with a specially-configured depending member having a "print head" having several print head pins thereon, each print head pin configured to deposit a single microscopic sample of material onto a slide. The robotic arm is then traversed over each of the slides positioned on the platter.

A robotic microarrayer for spotting solutions of biomolecules onto glass slides was developed by Brown and Shalon in 1994 and is disclosed in part in U.S. Patent. No. 5,807,522, issued September 15, 1998, incorporated by reference in its entirety. A prior art linear microarrayer is illustrated in Figs 1-9 in which:

FIG. 1 is a perspective view of the prior art linear microarrayer comprising a platter mounted for linear y-axis movement with respect to a table, a robotic arm mounted for x-axis movement with respect to the table located above the table on a bracket, and a depending print head mounted to the bracket for z-axis movement; FIG. 2 is an enlarged perspective view of the prior art platter of FIG. 1 wherein the platter has a pattern of raised alignment knobs for aligning a matrix of slides along x- and y-axes of the platter;

FIG. 3 is an enlarged, fragmentary perspective view of the prior art platter, specifically with reference to the area marked in of FIG. 2; FIG. 4 is a perspective view of an example of a prior art sample tray typically employed with the prior art platter of FIGS. 1-3; FIG. 5 is a perspective view of an example of a prior art rack of print head pins typically employed with the prior art print head of FIG. 1;

FIG. 6 is a perspective view of the prior art linear microarrayer of FIG. 1 wherein the print head has been traversed along the x-axis to be aligned with a washing station and traversed in oscillating fashion along the z-axis to insert the print head into and withdraw it from the washing station;

FIG. 7 is a perspective view of the prior art linear microarrayer of FIG. 1 wherein the print head has been traversed along the x-axis to be aligned with a drying station and traversed in oscillating fashion along the z-axis to insert the print head into and withdraw it from the drying station;

FIG. 8 is a perspective view of the prior art linear microarrayer of FIG. 1 wherein the print head has been traversed along the x-axis to be aligned with a sample plate and traversed in oscillating fashion along the z-axis to insert the print head into and withdraw it from the sample plate; and FIG. 9 is a perspective view of the prior art linear microarrayer of FIG. 1 wherein the print head has been traversed along the x- and y-axes to be aligned in a serpentine-like path fashion with each of the slides on the platter in succession and traversed in oscillating fashion along the z-axis to contact the print head with and withdraw it from each of the slides in succession to deposit a sub-microarray on each slide.

Referring now to Figs. 1-9, a microarrayer 10 comprises a square platter 12 mount mounted for linear y-axis movement with respect to a table 14 upon a linear slide 16 and powered by a first motor 18. The table 14 further includes an arch structure 20 comprising a pair of legs 22 interconnected at upper portions thereof by a cross member 24. The cross member 24 defines rails on which a robotic arm 26 is mounted for linear x-axis movement via a linear slide 28 and powered by a second motor 30.

The robotic arm 26 preferably comprises a body 32 defining rails on which a print head 34 is mounted for linear z-axis movement via a linear slide 36 and powered by a third motor 38. The first, second and third motors 18, 30 and 38, respectively, are known members for imparting linear movement to the slides 16, 28 and 36, respectively.

The print head 34 is a well-known member typically comprising a matrix of closely-spaced print head pins 40 biased by a spring (not shown) to perform the microarray deposition function.

Other typical components employed with prior art linear microarrayers 10 include a washing station 42, a drying station 44 that is fluidly interconnected to a vacuum source 46, and a sample plate 48.

By way of background and as shown in detail in FIGS. 2-3, the platter 12 comprises a square member 50 having a pattern 52 of raised alignment knobs 54 defining a plurality of slide-receiving areas 57. Several slides 58 are placed within these areas 56. The knobs 54 serve to retain the slides 58 in place during deposition of microarrays thereon. FIGS. 2-3 show that the square member 52 can include a tray 60 typically located at a corner portion thereof adapted to receive the sample plate 48 therein. The location of the sample plate 48 on the platter 12 provides a common reference location for a controller 56 for the linear microarrayer 10.

FIG. 4 shows an example of the sample plate 48 typically employed with the prior art platter 12 of FIGS. 1-3. The sample plate 48 typically comprises a rectangular member 62 having a closely-aligned matrix of wells 64 therein configured to receive a predetermined volume of material for deposition by the microarrayer 10. FIG. 5 shows an example of a prior art rack 68 of print head pins 40 disposed within protective sheaths 66. These print head pins 66 are loaded into the print head 34 typically in a matrix-like fashion for creating microarrays having a geometric pattern corresponding to the print head matrix. hi use, after a predetermined number of print head pins 40 have been installed on the print head 34 and this information fed to the controller 56, the platter 12 is typically positioned in a "home" position where the sample plate 48 located on a corner of the platter 12 is positioned adjacent the side-by-side washing and drying stations 42 and 44, respectively. The print head 34 is typically positioned along the x- and y-axes in vertical alignment above the washing station 42 and is then lowered and raised in oscillating fashion along the z-axis to insert the print head pins into and withdraw them from the washing station 42. This movement, and subsequently described x-, y- and z-axis movements are accomplished by the controller 56 sending signals to the first, second and third motors 18, 30 and 38 to actuate the first, second and third slides 16, 28 and 36, respectively. Then, as shown in FIG. 7, the print head 34 is traversed along the x-axis into alignment with the drying station 44 and is traversed in oscillating fashion along the z- axis to insert the print head 34 into, and withdraw it from, the drying station 44. The controller 56 typically sends a signal to the vacuum source 46 as the print head pins 40 descend into the drying station 44 to withdraw by suction any remaining material and washing fluid from the pins 40. As is commonly known, the positioning of the print head 34 within the washing station 42 and subsequently within the drying station 44 is often repeated for multiple cycles to ensure an effective cleaning of the print head pins 40.

FIG. 8 shows the next typical location of the print head 34 with respect to the table 14 wherein the print head 34 has traversed along the x-axis into alignment with the sample plate 48 and has traversed in oscillating fashion along the z-axis to insert the print head 34 into, and withdraw it from, the wells 64 of the sample plate 48. This descent of the print head pins 40 into the wells 64 (obviously containing a volume of material desired to be deposited on the slides 58 of the linear microarrayer 10) accumulates a small volume of the material to be deposited within each of the print head pins 40.

FIG. 9 shows the prior art linear microarrayer 10 wherein the print head 34 is traversed along the x- and y-axes in a serpentine path 70 over each of the slides 58 on the platter 12. As is well known, the print head 34 also traverses in oscillating fashion along the z-axis to contact the print head pins 40 with, and raise them from, each of the slides 58 in succession to deposit a sub-microarray on each slide along the serpentine path 70.

As described above, the linear microarrayer 10 is a well-known device for making DNA and other microarrays, which are now widely used for biological studies. As shown in the Brown '522 Patent as well as in FIGS. 1-9, known microarrayer technology uses a single print head manipulated linearly along the x-, y- and z-axes to take samples from the sample plate 48 and to deposit the samples onto slides 58.

Since many thousands of DNA samples are typically "spotted" onto each of the slides 58, fabrication of the microarrays can take a substantial amount of time. For example, if an array of 20,000 "spots" is to be created on each of one hundred slides positioned on the square platter 12 with twenty-five print head pins 40 provided on the print head 34, then the arm 26 mounting the print head 34 must thereby make eight hundred passes over each of the one hundred slides. This process can take many hours, even days, to complete auseable set of microarrayed slides, costing a laboratory valuable research time and machine down time. Further, because the square platter 12 and robotic arm 26 typically move linearly, the footprint required by the microarrayer 10 typically occupies a large amount of valuable laboratory space.

SUMMARY OF THE INVENTION The microarrayer of the present invention comprises a platter mounted for rotary movement about a vertical axis and comprises at least one and preferably multiple robotic arms, each with a print head for distribution of microarrays on slides. The rotary motion of the platter rather than linear movement forms a smaller arm travel distance and a more efficient method of creating microarrays upon multiple, often many, slides. In addition, the use of rotary motion permits multiple robotic arms to be employed in the creation of the microarrays. Further, the use of multiple robotic arms and print heads deposits the microarrays on the slides much faster.

The rotary microarrayer spots samples (such as DNA or, protein,) from microtiter sample plates onto microscope slides using multiple robotic arms. The microtiter sample plates can either be placed onto the rotating circular platter or adjacent thereto next to washing and drying stations. Slide rails extend radially outwardly from a bearing bracket suspended above the platter center axis, upon which a print head is driven linearly from center to circumference.

As in the prior art, the print head comprises print head pins for picking up fluid and depositing in a microarray pattern. A z-axis motor drops and lifts the print head as needed to accomplish the washing, drying, sample collection and microarray deposition functions.

Preferably, the microtiter sample plates lie adjacent to the periphery of the platter and are filled with the samples to be spotted. Outside the microtiter plates, relative to the platter, lay a wash station for washing the print head pins, and a dry station for drying them. The print heads simultaneously pick up samples from the microtiter plates, slide toward the center, and drop down to spot the microscope slides that are linearly and radially placed on the platter. The platter then rotates one position to the next row of slides, and the print heads spot again. This process repeats until a full revolution of the platter is made. The print head pins are then washed and dried, and new samples (from the same or replacement sample microtiter plates) are picked up. The spotting is repeated until all samples have been spotted (microarrayed).

Through the simultaneous use of multiple print heads, the speed of microarray production is increased in proportion to the increase in print head number. Further, the multiple print heads are accommodated by a rotary format, as opposed to the linear format used in prior art.

In one aspect, the invention relates to an apparatus for printing microarrays of at least one substance on at least one slide comprising a base, a platter mounted to the base for rotational movement about a z-axis, at least one arm mounted to the base above the platter for radial movement with respect to the z-axis of the platter, and a print head mounted to each of the at least one arm for reciprocating movement along the z-axis. The print head preferably has at least one substance-dispensing device thereon. The at least one substance can thereby be printed onto the at least one slide in the form of a microarray by the incremental rotational movement of the platter about the z-axis, the radial movement of the at least one arm, and by the z-axis movement of the print head. hi various embodiments of the invention, a controller can also be provided that is operably interconnected to the platter, to the at least one arm and to the print head for controlling the movement of the platter, the at least one arm and the print head.

The platter can be circular. The at least one slide can comprise several slides arranged on the platter in a predetermined configuration. The at least one arm can comprise at least two arms mounted to the base above the platter for independently-controllable radial movement with respect to the z-axis of the platter. A bracket can be mounted to the base above the platter and aligned with a center portion of the platter, wherein the bracket can include a plurality of mounting portions each adapted to receive an end of the at least one arm. The at least one arm can comprise a plurality of arms each having a first end mounted to the bracket mounting portion and a second end mounted to the base. Each of the plurality of arms can be selectively mounted to any one of the plurality of mounting portions of the bracket. The plurality of arms can thereby be arranged in various configurations of angular positions with respect to the platter. hi another aspect, the invention relates to a method of printing microarrays of at least one substance on at least one slide comprising the steps of: loading a print head with the at least one substance; positioning the print head over the slide; depositing the at least one substance on the print head onto a first location on the at least one slide; rotationally Indexing the slide about an axis generally normal to the at least one slide; and depositing the at least one substance on the print head onto a second location on the at least one slide.

In various embodiments of the invention, the method can further include the step of radially indexing the print head with respect to the axis; and depositing the at least one substance on the print head onto a third location on the at least one slide.

These steps can be repeated until the at least one slide has a predetermined number of deposits thereon.

BRIEF DESCRIPTION OF THE DRAWINGS OF THE INVENTION hi the drawings:

FIG. 10 is a perspective view of a rotary microarrayer of the present invention comprising a platter mounted to a support structure for rotary movement about the z- axis with respect to a table, at least one robotic arm mounted for x-axis movement with respect to the table located above the table on a bracket, and a depending print head mounted to the bracket for z-axis movement. FIG. 10A is a perspective view of an alternative configuration of the rotary microarrayer arranged similarly to that shown in FIG. 10 but with a microtiter plate located on the table upon a linear slide for y-axis movement relative to the table.

FIG. 11 is a perspective view of the rotary microarrayer of FIG. 10 wherein the print head has traversed along the x-axis into alignment with a washing station and traversed in oscillating fashion along the z-axis to insert the print head into and withdraw it from the washing station.

FIG. 12 is a perspective view of the rotary microarrayer of FIG. 10 wherein the print head has traversed along the x-axis into alignment with a drying station and traversed in oscillating fashion along the z-axis to insert the print head into and withdraw it from the drying station.

FIG. 13 is a perspective view of the rotary microarrayer of FIG. 10 wherein the print head has traversed along the x-axis into alignment with a sample plate and traversed in oscillating fashion along the z-axis to insert the print head into and withdraw it from the sample plate.

FIG. 14 is a perspective view of the rotary microarrayer of FIG. 10 wherein the platter has been rotated about the z-axis and the print head has traversed along the x- axis into alignment, in a rotary/spiral-like fashion, with each slide on the platter in succession and traversed in oscillating fashion along the z-axis to contact the print head with each of the slides in succession to deposit a sub-microarray on each slide.

FIG. 15 is a schematic drawing of the rotary microarrayer of FIG. 10 showing alternate locations for additional robotic arms at angularly spaced locations about a center bearing portion preferably coaxial with the rotary platter. DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring now to the drawings and to Fig. 10, in particular, a rotary microarrayer 110 comprises a generally circular platter 112 mount mounted for rotary movement about the z-axis with respect to a table 114 upon a rotary bearing 116 and powered by a first motor 118. The table 114 further includes an arch structure 120 comprising a pair of legs 122 interconnected at upper portions thereof by at least one cross member 124. When more than one cross member 124 is employed, the cross members 124 terminate at a central bearing portion 180 which suspends the cross members 124 above the table 114 by a bracket 182. Each cross member 124 defines rails on which a robotic arm 126 is mounted for linear x-axis movement via a linear slide 128 and each is powered by a second motor 130. The first motor 118 can comprise any well-known laboratory-type rotary platter motor such as a 200000RT Series rotary platter motor available from Parker Motion Control, a division of Parker-Harmefin Corporation, Harrison City, Pennsylvania. The second motor 130 can comprise any of many well-known linear motors as is well known in the art. Each robotic arm 126 preferably comprises a body 132 defining rails on which a print head 134 is mounted for linear z-axis movement via a linear slide 136 and powered by a third motor 138. The first motor 118 and each of the second and third motors 130 and 138 respectively corresponding to each of the robotic arms 126, are known members for imparting linear movement to the slides 128 and 136, respectively.

The print head 134 is a well-known member typically comprising the matrix of closely-spaced pin-like print head pins 140 biased by a spring (not shown) to perform the microarray deposition function as described with respect to the print head 34 and the print head pins 40 in the Background section of this specification. Other typical components typically employed with prior art linear microarrayers 10 are also included with respect to the rotary microarrayer 110 of this invention — but preferably the rotary microarrayer 110 includes one of these typical components corresponding to each of the robotic arms 126. Thus, in the example of the rotary microarrayer 110 shown in FIG. 10, a washing station 142, a drying station 144 fluidly interconnected to a vacuum source 146 and a sample plate 148 are shown on each side of the table 114 for each of the robotic arms 126. Additional or fewer robotic arms 126 (and thus additional or fewer components 142-148) can be employed without departing from the scope of this invention. Further, the drying stations 144 can be interconnected to a common vacuum source 146. hi order to accomplish the rotary configuration of the rotary microarrayer 110, the rotary motor 118 interconnected to the bearing 116 supports a central shaft 184 which extends along the z-axis through the bearing 180 as well. A central portion 186 of the platter 112 is mounted to the shaft 184 to permit the rotary platter 112 to rotate with the central shaft 184. hi use, after a predetermined number of print head pins 140 have been installed on the print head 134 and this information fed to the controller 156, the platter 112 is positioned in a "home" position where the sample plate 148 located adjacent to the platter 112 is positioned adjacent to side-by-side washing and drying stations 142 and 144, respectively, extending outwardly from and along a radius of platter 112. As shown in FIG. 11, each print head 134 is positioned along the x-axis in vertical alignment above the corresponding washing station 142 and can be lowered and raised in oscillating fashion along the z-axis to insert the print head 134 into and withdraw it from the corresponding washing station 142.

This x- and z-axis movement, and subsequently described x- and z-axis movements are accomplished by the controller 156 sending signals to each of the second and third motors 130 and 138 to actuate the second and third slides 128 and 136, respectively. The platter 112 can be positioned in an (r,θ) coordinate manner by actuating the first motor 118 to rotate the central shaft 184 within the bearings 116 and 180. Each of the print heads 134 employs the circular coordinate (r,θ) positioning as well by coordinating the x-axis movements with the rotary movement of the platter 112.

Then, as shown in FIG. 12, each of the print heads 134 is traversed along the x-axis into alignment with the corresponding drying station 144 and traversed in oscillating fashion along the z-axis to insert the print head 134 into and withdraw it from the corresponding drying station 144. As the print head pins 140 of the particular print head 134 descends into the corresponding drying station 144, the controller 156 typically sends a signal to the vacuum source 146 to apply suction for removal of any remaining material and washing station fluid from the pins 140.

As was described in the Background section, the positioning of the print head 134 within the washing station 142 and subsequently within the drying station 144 can repeated for multiple cycles to ensure an effective cleaning of the print head pins 140. FIG. 13 shows the next location of me print heads 134 with respect to the table 114 after the print heads 134 have traversed along the x-axis into alignment with the sample plate 148 and traversed in oscillating fashion along the z-axis to insert each of the print heads 134 into (and subsequently to be withdrawn from) the wells of the corresponding sample plate 148. This descent of the print head pins 140 into the wells that contain a volume of material desired to be deposited on slides 158 (positioned on the rotary microarrayer 110) accumulates a small volume of the material to be deposited within each of the print head pins 140.

FIG. 14 shows the rotary microarrayer 110 at the stage wherein each print head 134 has traversed along the x-axis in an orderly radial path 170 and is positioned over slides 158 that are arrayed linearly on the rotary platter 112. Each print head 134 has also traversed in oscillating fashion along the z-axis to contact the print head pins 140 of each of the print heads 134 with (and subsequently to be raised from) each of the slides 158 positioned along the particular robotic arm's radial path 170. During this contact, the print head pins 140 deposit a sub-microarray on each slide 158. Once the radial path 170 has been completed, the controller 156 issues a signal to the first motor 118 to step-wise rotate the shaft 184, and thereby the platter 112, to a next successive angular position. Then each of the print heads 134 traverses again in the opposite direction along the x-axis to deposit microarrays on slides 158 that are arrayed along the next angular path 170.

Several advantages become apparent by examination of the rotary microarrayer 110 configuration of FIGS. 10-14. First, the rotary platter 112, having a circular configuration, occupies a far smaller footprint in a laboratory than a similarly-configured prior art linear microarrayer 10 because the rotary platter 112 does not need to slide linearly to position the single print head as in the prior art.- Second, the rotary configuration permits multiple robotic arms 126 to be employed, as illustrated in FIG. 15.

Although the drawings show multiple print heads 134 acting in unison, i.e., having the same general radial and angular position with respect to the platter 112, each of the print heads 134 can be independently controlled by the controller 156. For example, if one of the print heads 134 had a different number of print head pins 140 than another print head 134 (thus requiring a different number of passes to place the same number of spots on the slides), the controller 156 need merely adjust the x-axis positioning of the skewed print head(s) 134 and control the platter 112 to refrain from a repositioning step until each of the print heads 134 has completed its prescribed spotting along its corresponding angular path 170.

FIG. 15 is a schematic drawing of the rotary microarrayer 110 showing alternate locations for cross members 124 which are interconnected at one end to the table 114 by legs 122 and at an inner and upper end to the bearing bracket 182. As can be seen in Fig. 15, this invention clearly contemplates more than two robotic arms 126 — the number of robotic arms 126 limited only by the available space on the platter 112. With larger platters 112, it is believed that up to and exceeding eight robotic arms 126 can be provided for simultaneous spotting for slides 158 located on the platter 112.

Through the use of multiple print heads 134 on multiple robotic arms 126, the speed of making microarrays is increased in proportion to the increase in the number of print heads 134 that are accommodated by the rotary fonnat of the rotary microarrayer 110.

The proportional increase in the speed of microarray deposition is believed even to exceed a direct fractional relationship. For example, at first glance, it appears that adding a second robotic arm 126 with a second print head 134 should permit spotting of the same number of slides with the same number of spots in exactly one-half of the time. However, it is expected that the increase in speed will be even greater. First, the paths traveled by the print heads 134 are shorter with the rotary microarrayer 110 — i.e., one or more straight radial paths 170, compared to the lengthy serpentine path required by the prior art microarrayer. Second, the sample plate 148 which serves as the "home" position to which the print heads 134 must return repeatedly for loading with additional sample fluid after the sample fluid contained within the pins 134 has been exhausted is located much closer to the slides. For example, compare the maximum distance of a radius r of the platter 112 versus a distance of 2rV2 with a similar size square platter 12 having sides equal to 2r. These and other factors contribute to this basis for the unexpected benefits of the performance of the rotary table compared to the prior art. It should be noted that FIG. 10A shows an alternative configuration of the rotary microarrayer arranged similar to that shown in FIG. 10 but with the microtiter plate 148 located on the table 114 upon a linear slide 149 for y-axis movement relative to the table. This configuration permits additional slides 158 to be positioned on the platter 112 while the slide 149 allows for sufficient y-axis movement of the plate 148 to reposition the plate 148 relative to the corresponding print head 134 for accumulating additional samples by the pins 140 thereof.

While particular embodiments of the invention have been shown, it will be understood, of course, that the invention is not limited thereto since modifications may be made by those skilled in the art, particularly in light of the foregoing teachings. Reasonable variation and modification are possible within the scope of the foregoing disclosure of the invention without departing from the spirit of the invention.

Claims

CLAIMSThe embodiments for which an exclusive property or privilege is claimed are defined as follows:

1. An apparatus for printing microarrays of at least one substance on at least one slide comprising: a base; a platter mounted to the base for rotational movement about a z-axis; at least one arm mounted to the base above the platter for radial movement with respect to the z-axis of the platter; and a print head mounted to each of the at least one arm for reciprocating movement along the z-axis, the print head having at least one substance-dispensing device thereon; whereby the at least one substance can be printed onto the at least one slide in the form of a microarray by the incremental rotational movement of the platter about the z-axis, the radial movement of the at least one arm, and by the z-axis movement of the print head.

2. The apparatus of claim 1 and further comprising a controller operably interconnected to the platter, to the at least one arm and to the print head for controlling the movement of the platter, the at least one arm and the print head.

3. The apparatus of claim 2 wherein the platter is circular.

4. The apparatus of claim 3 wherein the at least one slide comprises several slides arranged on the platter in a predetermined configuration.

5. The apparatus of claim 4 wherein the at least one arm comprises at least two arms mounted to the base above the platter for independently-controllable radial movement with respect to the z-axis of the platter.

6. The apparatus of claim 4 and further comprising a bracket mounted to the base above the platter and aligned with a center portion of the platter, wherein the bracket includes a plurality of mounting portions each adapted to receive an end of the at least one arm.

7. The apparatus of claim 6 wherein the at least one arm comprises a plurality of arms each having a first end mounted to the bracket mounting portion and a second end mounted to the base.

8. The apparatus of claim 7 wherein each of the plurality of arms can be selectively mounted to any one of the plurality of mounting portions of the bracket whereby the plurality of arms can be arranged in various configurations of angular positions with respect to the platter.

9. The apparatus of claim 1 wherein the platter is circular.

10. The apparatus of claim 1 wherein the at least one slide comprises several slides arranged on the platter in a predetermined configuration.

11. The apparatus of claim 1 wherein the at least one arm comprises at least two arms mounted to the base above the platter for independently-controllable radial movement with respect to the z-axis of the platter.

12. The apparatus of claim 1 and further comprising a bracket mounted to the base above the platter and aligned with a center portion of the platter, wherein the bracket includes a plurality of mounting portions each adapted to receive an end of the at least one arm.

13. The apparatus of claim 12 wherein the at least one arm comprises a plurality of arms each having a first end mounted to the bracket mounting portion and a second end mounted to the base.

14. The apparatus of claim 13 wherein each of the plurality of arms can be selectively mounted to any one of the plurality of mounting portions of the bracket whereby the plurality of arms can be arranged in various configurations of angular positions with respect to the platter.

15. A method of printing microarrays of at least one substance on at least one slide comprising the steps of: loading a print head with the at least one substance; positioning the print head over the slide; depositing the at least one substance on the print head onto a first location on the at least one slide; rotationally Indexing the slide about an axis generally normal to the at least one slide; and depositing the at least one substance on the print head onto a second location on the at least one slide.

16. The method of claim 15 and further comprising the step of radially indexing the print head with respect to the axis; and depositing the at least one substance on the print head onto a third location on the at least one slide.

17. The method of claim 16 wherein the step of radially indexing the print head is repeated until the at least one slide has a predetermined number of deposits thereon before the step of rotationally indexing the at least one slide.

18. The method of claim 17 wherein the at least one slide comprises several slides.

19. The method of claim 18 wherein these steps are repeated until the at least one slide has a predetermined number of deposits thereon.

20. The method of claim 15 wherein the at least one slide comprises several slides.

21. The method of claim 15 wherein these steps are repeated until the at least one slide has a predetermined number of deposits thereon.