Method and apparatus for delivery of submicroliter volumes onto a substrate

a technology of submicroliter volume and substrate, applied in the field of sample dispensing systems, can solve the problems of pin tools being difficult to use pin tools can be problematic for high throughput systems, and pin tools cannot be used in contact dispensing situations,

Inactive Publication Date: 2006-02-02
SEQUENOM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0019] By virtue of the pin tool design herein, it is possible to transfer the sample to a pre-determined locus on a substrate that already has pre-deposited material, such as matrix, cells, such as bacterial or mammalian cells, protein crystals and other materials sensitive to contact. Since the instant tools provided herein rely on inertial forces for delivery, delivery of liquids is primarily dependent upon the momentum of the liquid in the slotted tool, not on the relative surface tensions of the pin and the substrate for the liquid. As one result, the pin tools provided herein permit accurate and controlled delivery of defined volumes by selection of the velocity of the tool at impact or as it reaches it the substrate and is stopped prior to contact.

Problems solved by technology

Pin tools also can be problematic for high throughput systems because the pins may have to be changed if different sample volumes are desired, or if the nature of the liquid sample is changed to avoid sample contamination.
In addition, pin tools cannot be used in situations where contact dispensing where there is a risk of damage to a fragile preloaded sample, such as for mass spectrometric analyses in which samples are deposited on loci that have preloaded material, such as matrix material for matrix-assisted laser desorption (MALDI).
When a sample target is preloaded or prespotted with the porous matrix material required for mass spectrometry, direct contact by the solid pin with the matrix material can crush the material.
Such piezoelectric delivery systems are susceptible to dispensing satellite droplets on a target location because of surface tension effects.
Piezoelectric systems also may be prone to variations in voltage and frequency among different tips, which results in variation between the volume of liquid sample dispensed from different individual tips.

Method used

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  • Method and apparatus for delivery of submicroliter volumes onto a substrate
  • Method and apparatus for delivery of submicroliter volumes onto a substrate
  • Method and apparatus for delivery of submicroliter volumes onto a substrate

Examples

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example 1

[0123] A flat substrate containing an array of less hydrophobic elements surrounded by more hydrophobic elements, was prepared with an array of photoresist elements. To prepare the array, silicon dioxide (SiO2) was grown on silicon wafers to a height of 3025 angstroms, ±5%. Alternatively, the SiO2 can be grown to a height of about 1050 angstroms. This process is performed by a “wet oxidation” method in which H2 and O2 gases are used in converting the Si to SiO2.

[0124] A photoresist material (such as “AZ 111 XFS” photoresist from Clariant Corporation of Charlotte, N.C., USA) was spun onto the SiO2 to a thickness of 0.2 μm to 1.22 μm, with a height of about 1.0 μm. The photoresist was solidified by baking at 65 degrees Celsius for two to three minutes. The surface was then exposed to light of 365 nm wavelength through a mask that blocked light at the target locations. The photoresist that was exposed to light in the unmasked portions of the substrate was then washed off with a phosph...

example 2

[0126] In another process provided herein, a microarray was produced with a flat starting substrate having an array of SiO2 elements surrounded by a silane surface, thereby creating an array of elements less hydrophobic than the surrounding area. The resulting substrate has target locations that are bare silicon dioxide, and the surrounding regions are silated with DMDCS.

[0127] Silicon dioxide was grown on silicon wafers to a height of 3025 Angstroms±5%. Alternatively, the SiO2 can be grown to a height of about 1050 angstroms. This process is performed by a “wet oxidation” method in which H2 and O2 gases are used in converting the Si to SiO2.

[0128] The resulting substrate was patterned with “MEGAPOSIT” SPR 900-0.8 photoresist from Shipley Company, L.L.C. of Marlborough, Mass., USA in the manner described above in Example 1. The wafer was then baked at 70° C. for 30 minutes to remove any remaining solvents. The patterned substrate was silated with 3.5% DMDCS for twenty minutes, as ...

example 3

[0129] In another process, a microarray was produced using a flat substrate having an array of SiO2 elements surrounded by a TEFLON® (polytetrafluoroethylene (PFTE)) surface, to create an array of target elements less hydrophobic than the surrounding area.

[0130] Silicon dioxide was grown on silicon wafers to a height of 3025 Angstroms±5%. Alternatively, the SiO2 can be grown to a height of about 1050 angstroms. This process is performed by a “wet oxidation” method in which H2 and O2 gases are used in converting the Si to SiO2.

[0131] The resulting substrate was patterned with “MEGAPOSIT” SPR 900-0.8 photoresist from Shipley Company, L.L.C. of Marlborough, Mass., USA as described above for Example 1. The resulting substrate was baked as in Example 2.

[0132] The patterned substrate was coated with a TEFLON® (polytetrafluoroethylene (PFTE)) coating, such as “PerFluoroCoat” from Cytonix Company of Beltsville, Md., USA, to a height of 148 to 1200 Angstroms. The photoresist pads were rem...

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Abstract

A slotted pin tool, a delivery system containing the pin tool, a substrate for use in the system and methods using the pin tool and system are provided. The slotted pin tool contains a plurality of pins having slotted ends designed to fit around each loci of material deposited on a surface, such as a microarray, without contacting any of the deposited material. Sample is delivered by contacting the pin tool with the surface; the amount delivered is proportional to the velocity of the pin tool as it contacts the surface or the velocity of the liquid when movement of the pin is halted.

Description

RELATED APPLICATIONS [0001] Benefit of priority under 35 U.S.C. §119(e) to U.S. provisional application Ser. No. 60 / 244,404, filed Oct. 30, 2000, to Chao Lin et al., entitled “METHOD AND APPARATUS FOR DELIVERY OF SUBMICROLITER VOLUMES ONTO A SUBSTRATE” is claimed herein. The subject matter of the provisional application is incorporated by reference in its entirety.BACKGROUND [0002] 1. Field of the Invention [0003] The invention relates to sample dispensing systems and, more particularly, to the delivery of liquid samples onto substrate, such as a microarray, for laboratory analysis. [0004] 2. Description of the Background Art [0005] Genetic sequencing efforts, such as the Human Genome project, have produced vast amounts of information for basic genetic research that have proven useful in developing advances in health care and drug research. These advances are possible because of improvements in engineering and instrumentation that provide advanced tools for the biotechnology communi...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N1/10G01D15/04G01N27/62B01J4/00B01J19/00B01L3/02C40B40/06C40B40/10C40B60/14G01N27/64G01N33/53G01N35/00G01N35/02G01N35/10
CPCB01J19/0046Y10T436/2575B01J2219/00527B01J2219/00585B01J2219/0059B01J2219/00596B01J2219/00605B01J2219/00612B01J2219/00619B01J2219/00659B01J2219/00677B01J2219/00686B01J2219/00689B01J2219/00691B01J2219/00722B01J2219/00725B01L3/0244B01L3/0248B01L2200/0657B82Y30/00C40B40/06C40B40/10C40B60/14G01N35/0099G01N35/028G01N35/10G01N35/1016G01N35/1065G01N2035/00158G01N2035/1037G01N1/10Y10T436/119163Y10T436/24Y10T436/112499Y10T436/11B01J2219/00387B01J2219/00529B01J2219/00608B01L3/02
Inventor YAO, XIAN-WEILIN, CHAOHEANEY, PAULBECKER, THOMASHANSON, AARONWILLIS, MICHAEL C.
Owner SEQUENOM INC
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