WO2004063728A1 - Ellipsometre de reseau induit par un absorbant puissant - Google Patents

Ellipsometre de reseau induit par un absorbant puissant Download PDF

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Publication number
WO2004063728A1
WO2004063728A1 PCT/US2003/041601 US0341601W WO2004063728A1 WO 2004063728 A1 WO2004063728 A1 WO 2004063728A1 US 0341601 W US0341601 W US 0341601W WO 2004063728 A1 WO2004063728 A1 WO 2004063728A1
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WIPO (PCT)
Prior art keywords
target
probe
light
array
probes
Prior art date
Application number
PCT/US2003/041601
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English (en)
Inventor
William M. D. Rassman
David Ralin
Original Assignee
Maven Technologies, Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Maven Technologies, Llc filed Critical Maven Technologies, Llc
Priority to AU2003300433A priority Critical patent/AU2003300433A1/en
Publication of WO2004063728A1 publication Critical patent/WO2004063728A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/21—Polarisation-affecting properties
    • G01N21/211—Ellipsometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/21—Polarisation-affecting properties
    • G01N21/211—Ellipsometry
    • G01N2021/213—Spectrometric ellipsometry

Definitions

  • the present invention relates to biomolecule microarrays, more particularly to making observations of microarrays by way of total internal reflection ellipsometry or ellipsometry, and especially to the use of optically absorbent tags for increasing the signal in an ellipsometric measurement of a microarray.
  • DNA-DNA hybridization interactions can be detected and measured using a microarray (see , Shoemaker Nat Gen 1996 14 450, Cheung Nat Gen 1998 18 155).
  • Other microarray formats utilizing proteins MacBeath G & Schreiber SL (2000). Printing proteins as microarrays for high throughput function determination. Science 289(5485): 1760- 1763. MacBeath G, Koehler AN, & Schreiber SL (1999). Printing small molecules as microarrays and detecting protein-ligand interactions en masse. J. Am. Chem. Soc. 121: 7967-7968) and carbohydrates (http://genome4.cpmc.columbia.edu/researcher/wang_d.html) are developing.
  • TIR Total internal reflection
  • TIR spectroscopy data is presented as plots of reflected intensity versus wavelength. It is well known that these plots are polarization-dependent, with the light polarized parallel to the plane of incidence (s-polarized light) being more strongly affected by the presence of the absorbing material than light of perpendicular polarization (p-polarized light).
  • the presence of an optical absorbing material affects the ratio of s- to p-polarization in TIR-reflected light
  • Another way in which the presence of an absorber affects the s- to p- ratio of TIR reflected light is through "anomalous dispersion" in the refractive index of a material at wavelengths near the absorbance maximum. At wavelengths higher than the absorbance maximum, the evanescent field penetration is greater than it would be in the absence of the absorbing material.
  • the ratio of s- to p-polarized TIR light intensity can be used to detect refractive index changes associated with changes in surface density of the rarefied medium.
  • the surface-binding of target biomolecules tagged with optically absorbing "labels” can induce far greater changes in polarization ratio in a biomolecular nanoarray than the binding of unlabeled, optically clear (non-absorptive) native biomolecules.
  • this invention is based on the principle that certain molecules absorb light at characteristic wavelengths, and this can be used to generate a significant signal indicative of its presence by interrogation by polarized light in an evanescent field at the characteristic wavelength.
  • the unique presence of such a molecule in or attached to a hybridized target in a microarray or nanoarray provides for an easily sensed signal that hybridization has occurred, and that the target is present in the sample.
  • the signal is sensed as a change in light intensity because the tag molecule operates by absorbing, or rotating the plane of polarization, of the "interrogating" polarized light.
  • Sensing of the output can be by an ellipsometer, or an evanescent wave-based device.
  • the exposure to a nanoarray, at various locations in which different hybridization reactions occur, of a variety of such absorbing molecules can be used to tag different subsets of the array which produce signals at different wavelengths.
  • large numbers of hybridization subsets of the array can be characterized. If sample materials from different sources carry molecules with different absorbing characteristics, the presence of the different sample materials at each point in the array may be measured and compared by interrogating the array with light at particular wavelengths. Relative abundance of particular target materials in the respective samples may then be determined.
  • this invention is based on the recognition that the presence of certain molecules or molecular structures
  • TIR surface at which interrogating polarized light is directed in a manner to generate an evanescent field encompassing those complexes, is operative to augment the localized rotation of the plane of polarization of the light over what is achieved in the absence of such a marker.
  • the marker typically operates as a light absorber at a characteristic wavelength, but the marker need not be an absorber itself. Instead it may be operative to make the complex absorbing even though none of the constituents of the complex is absorbing in the absence of the other constituents. In some instances the absorber may only become active after washing with an activator.
  • the absorber may be attached to target molecules prior to hybridization.
  • the absorber may attach to probe/target pairs after hybridization.
  • the absorber may attach to the target after hybridization.
  • absorbers are operative to increase locally the rotation of the plane of polarization of the interrogating light and are responsive to interrogating light at characteristic wavelengths.
  • absorbers are operative to increase locally the rotation of the plane of polarization of the interrogating light and are responsive to interrogating light at characteristic wavelengths.
  • a schematic representation of the apparatus position of the filter is non-critical, so long as it is in the illumination arm
  • equipment included the following:
  • High-pixel-count camera Assembly including a prism or grating that allows interrogating light to reach the array at an angle for achieving TIR with respect to the plane of the array (as described in Imaging Device);
  • a flow cell is employed to deliver the sample to the array, and successive measurements are taken over the time course of the experiment, before introduction of the sample, during hybridization, and after washing.
  • the thickness variation of the CY3-tagged oligonucleotide from zero to one nm is intended to approximate the maximum surface coverage that could be achieved with a fluorescent label with an absorbtion coefficient of 150,000 at 550nm.
  • Fig. 2 illustrates a simulated Ellipsometry response over a lnm film thickness Change.
  • Check-ItTM Chips from Telechem International, Sunnyvale, CA, were processed and hybridized according to the manufacturer's instructions, with minor necessary modifications for our application.
  • a Check-ItTM Chip is a 25x75mm microarray printed with 70-mer oligonucleotides corresponding to human, mouse, and E. coli gene sequences, in 300 micron diameter spots, on a SuperAmine Microarray Substrate, in two identical subarrays. The probe concentration in the spots varies as well. It is provided with 50 :L of See-It Universal Probe Solution, 50:M concentration and labeled with CY3, a fluorescent dye with an absorbtion peak at 550 nm, which will differentially hybridize to the probe spots on the array.
  • FIG. 4 A QC image of the array from the manufacturer is shown in Fig. 4. This QC image is notable for the lack of consistency between the two "identical” subarrays.
  • the bright green spots are CY3 probe spots with maximal affinity for the target sequences, intended as the "saturating maximum response" for setting up confocal scanning / laser excitation microarray readers.
  • the processing and hybridization was performed as follows.
  • row 1, column 1 through 10 was analyzed, as was the "Max Spot" at row 10 column 1.
  • Local background level was determined by taking averaged measurements at the four corners of the array and interpolating. Signals within the presumptive spots (a 300 micron diameter circle) were averaged, and the difference between local background and each spot was calculated.
  • the slides are not compared to themselves before hybridizing and after, because the composition of the amine substrate surface changes substantially in response to the hybridization buffer itself, making comparisons difficult. Also, the procedure of un-mounting the array
  • ID from the TIR elements so that further processing can occur ensures that the array will be contaminated with index matching fluids.
  • Dyes usable in carrying out the present invention include those listed in Table 2 (this table occupies several pages).
  • T[ Human vision is insensitive to light beyond -650 nm, and therefore it is not possible to view the far- red&endash;fluorescent dyes by looking through the eyepiece of a conventional fluorescence microscope.
  • e Extinction coefficient at I max in cm -1 M -1 .
  • T e CY dyes and Alexa fluors are the most common in nucleic acid microarray analysis, being relatively easily to incorporate.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention concerne un substrat supportant un réseau de sondes; des molécules cibles fixées sur les sondes, une molécule absorbante sur le plan optique étant fixée sur chaque cible, chaque molécule absorbante répondant à un rayonnement d'une longueur d'ondes caractéristique et générant un signal indiquant la présence d'un ensemble sonde-cible dans le réseau; des éléments optiques permettant de diriger un rayonnement de ladite longueur d'ondes caractéristique sur le réseau; des éléments optiques et un instrument permettant de détecter chaque signal généré.
PCT/US2003/041601 2003-01-08 2003-12-30 Ellipsometre de reseau induit par un absorbant puissant WO2004063728A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003300433A AU2003300433A1 (en) 2003-01-08 2003-12-30 Strong-absorber-mediated array ellipsometer

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US43862003P 2003-01-08 2003-01-08
US60/438,620 2003-01-08

Publications (1)

Publication Number Publication Date
WO2004063728A1 true WO2004063728A1 (fr) 2004-07-29

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WO (1) WO2004063728A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006008112A1 (fr) * 2004-07-21 2006-01-26 Oc Oerlikon Balzers Ag Dispositif d'ellipsometrie a plate-forme de resonance

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5300423A (en) * 1991-01-30 1994-04-05 E. I. Du Pont De Nemours And Company Specific binding assay involving separation of light emissions
US5633724A (en) * 1995-08-29 1997-05-27 Hewlett-Packard Company Evanescent scanning of biochemical array
US5843651A (en) * 1994-09-22 1998-12-01 Abbott Laboratories Light scattering optical waveguide method for detecting specific binding events
WO2001035081A1 (fr) * 1999-11-12 2001-05-17 Surromed, Inc. Biodetection par resonance plasmonique de surface

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5300423A (en) * 1991-01-30 1994-04-05 E. I. Du Pont De Nemours And Company Specific binding assay involving separation of light emissions
US5843651A (en) * 1994-09-22 1998-12-01 Abbott Laboratories Light scattering optical waveguide method for detecting specific binding events
US5633724A (en) * 1995-08-29 1997-05-27 Hewlett-Packard Company Evanescent scanning of biochemical array
WO2001035081A1 (fr) * 1999-11-12 2001-05-17 Surromed, Inc. Biodetection par resonance plasmonique de surface

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006008112A1 (fr) * 2004-07-21 2006-01-26 Oc Oerlikon Balzers Ag Dispositif d'ellipsometrie a plate-forme de resonance

Also Published As

Publication number Publication date
AU2003300433A1 (en) 2004-08-10

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