Microvolume liquid dispenser suitable for microarrays and methods related thereto
First Claim
1. A microvolume liquid dispenser comprising a body, an outer sleeve extending from the body, and a reciprocating pin located within the outer sleeve, wherein the outer sleeve comprises a distal opening and the pin reciprocates relative to the sleeve between a distal position wherein a distal tip of the pin extends beyond the distal opening and a proximal position, wherein the outer sleeve and the reciprocating pin are configured to cooperatively form a reservoir when the pin is in the distal position and configured to cooperatively dispense, through a passage formed between a side of the distal opening and the pin, a predetermined microvolume amount of liquid from the reservoir when the pin moves in a cycle from the distal position to the proximal position then returns to the distal position.
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Abstract
Microvolume liquid dispensers that provide simple and inexpensive approaches to making cytology microarrays. In some embodiments, the dispensers comprise tips that comprise an outer sleeve, typically shaped like a funnel, that holds a reciprocating needle or pin. The tip of the pin slightly extends beyond the distal opening of the outer sleeve in one position, and is retracted in another position. When the pin is in the distal position the pin contacts the inner surfaces of the sleeve and blocks cytology liquid from flowing through the opening of the sleeve. Thus the pin and sleeve cooperate to form a reservoir behind the blockage. When the pin is pushed up into the sleeve, for example by touching the tip to a glass slide, a passage is formed between the outer surface of the pin and the inner surface of the sleeve. The liquid in the reservoir then flows through the passage and onto the slide. Removing the tip from the substrate moves the pin back to its original position, reforming the reservoir and leaving a predetermined microvolume amount of the liquid on the slide.
35 Citations
48 Claims
- 1. A microvolume liquid dispenser comprising a body, an outer sleeve extending from the body, and a reciprocating pin located within the outer sleeve, wherein the outer sleeve comprises a distal opening and the pin reciprocates relative to the sleeve between a distal position wherein a distal tip of the pin extends beyond the distal opening and a proximal position, wherein the outer sleeve and the reciprocating pin are configured to cooperatively form a reservoir when the pin is in the distal position and configured to cooperatively dispense, through a passage formed between a side of the distal opening and the pin, a predetermined microvolume amount of liquid from the reservoir when the pin moves in a cycle from the distal position to the proximal position then returns to the distal position.
- 8. A microvolume liquid dispenser tip comprising an outer sleeve and a reciprocating pin located within the outer sleeve, the outer sleeve comprising a distal opening and the pin reciprocating relative to the sleeve between at least a distal position wherein a distal tip of the pin extends slightly beyond the distal opening and a proximal position, wherein an inner surface of the sleeve and an outer surface of the pin are configured to cooperatively form a reservoir when the pin is in the distal position and wherein the sleeve and pin are configured to cooperatively dispense, through a passage formed between a side of the distal opening and the pin, a predetermined microvolume amount of liquid from the reservoir when the pin moves in a cycle from the distal position to the proximal position then returns to the distal position.
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15. A cytology microarray maker comprising
a frame, the frame operably connected to a body holding an array of microvolume liquid dispenser tips, at least two stages sized to support cytology microarrays, upright members operably attached to the body to move the body and the array of tips substantially normal to the stages between at least an extended position wherein the tips contact a cytology microarray substrate located on the stage and a retracted position wherein the tips do not contact the cytology microarray substrate, and at least one axial member disposed along the frame and operably connected to the upright members to provide a track along which the upright members, the body and the array of tips is movable along the track between the first and the second stage.
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26. A method of dispensing a microvolume of liquid comprising:
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a) providing a microvolume liquid dispenser tip containing the liquid, the tip comprising an outer sleeve and a reciprocating pin located within the outer sleeve, wherein the outer sleeve comprises a distal opening and the pin reciprocates relative to the sleeve between a distal position wherein a distal tip of the pin extends beyond the distal opening and a proximal position, wherein the outer sleeve and the reciprocating pin are configured to cooperatively dispense, through a passage formed between a side of the distal opening and the pin, a predetermined microvolume amount of liquid when the pin moves in a cycle from the distal position to the proximal position then returns to the distal position;
b) transiently contacting the distal tip and distal opening with a substrate thereby causing the pin to cycle; and
,c) during the cycle, dispensing the liquid to the substrate.
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34. A method of making a cytology microarray comprising:
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a) providing a frame holding a body holding an array of microvolume liquid dispenser tips, at least first and second stages sized to support cytology microarrays, upright members operably attached to the body to move the body and the array of tips substantially normal to the stages between at least an extended position wherein the tips contact a cytology microarray substrate located on the stage and a retracted position wherein the tips do not contact the cytology microarray substrate, and at least one axial member disposed along the frame and operably connected to the upright members to move the upright members, the body and the array of tips between the first and the second stage, wherein the first stage holds a cytology microarray template comprising an array of liquid cytological specimens and the second stage holds a cytology microarray substrate;
b) loading the array of tips with the liquid cytological specimens by transiently moving the array of tips into the liquid cytological specimens and suctioning up the liquid cytological specimens using capillary action;
c) moving the array of tips along the axial member to the second stage; and
d) making the cytology array by transiently contacting the array of tips with the cytology microarray substrate.
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45. A tip means for microvolume liquid dispensing comprising:
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a) an outer sleeve means for holding the liquid, b) a reciprocating pin means located within the outer sleeve for cooperatively dispensing, through a passage formed between a side of the outer sleeve means and the pin means, a predetermined microvolume amount of liquid when the pin moves in a cycle from a distal position to a proximal position then returns to a distal position.
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46. A means for making cytology microarrays comprising:
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a) a frame means for holding a body means, b) the body means for holding an array of tips means for dispensing a microvolume of liquid, c) at least two stage means for supporting cytology microarrays, d) at least two upright member means operably attached to the body for moving the body means substantially normal to the stage means, and e) at least one axial member means disposed along the frame and operably connected to the upright members for moving the upright member means between the two stage means.
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47. A method of dispensing a microvolume of liquid comprising the steps of:
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a) a step of providing a microvolume liquid dispenser tip means containing the liquid, the tip comprising an outer sleeve and a reciprocating pin located within the outer sleeve, wherein the outer sleeve comprises a distal opening and the pin reciprocates relative to the sleeve between a distal position wherein a distal tip of the pin extends beyond the distal opening and a proximal position, wherein the outer sleeve and the reciprocating pin are configured to cooperatively dispense, through a passage formed between a side of the distal opening and the pin, a predetermined microvolume amount of liquid when the pin moves in a cycle from the distal position to the proximal position then returns to the distal position;
b) transiently contacting the distal tip and distal opening with a substrate thereby causing the pin to cycle; and
,c) during the cycle, dispensing the liquid onto the substrate.
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Specification