Nanoparticles having oligonucleotides attached thereto and uses therefor

A method of detecting nucleic acid having at least two portions comprising:

• providing a substrate having a first type of nanoparticles attached thereto, the nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of a nucleic acid to be detected;
• contacting said nucleic acid with the nanoparticles attached to the substrate under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with said nucleic acid;
• providing a second type of nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to one or more other portions of the sequence of said nucleic acid;
• contacting said nucleic acid bound to the substrate with the second type of nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the second type of nanoparticles with said nucleic acid;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• providing a substrate having a first type of nanoparticles attached thereto, the nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of a nucleic acid to be detected;
• contacting said nucleic acid with the nanoparticles attached to the substrate under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with said nucleic acid;
• providing a second type of nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to one or more other portions of the sequence of said nucleic acid;
• contacting said nucleic acid bound to the substrate with the second type of nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the second type of nanoparticles with said nucleic acid;
• providing a binding oligonucleotide having a selected sequence having at least two portions, the first portion being complementary to at least a portion of the sequence of the oligonucleotides on the second type of nanoparticles;
• contacting the binding oligonucleotide with the second type of nanoparticles bound to the substrate under conditions effective to allow hybridization of the binding oligonucleotide to the oligonucleotides on the nanoparticles;
• providing a third type of nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to the sequence of a second portion of the binding oligonucleotide;
• contacting the third type of nanoparticles with the binding oligonucleotide bound to the substrate under conditions effective to allow hybridization of the binding oligonucleotide to the oligonucleotides on the nanoparticles;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• contacting a nucleic acid to be detected with a substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the substrate with said nucleic acid;
• contacting said nucleic acid bound to the substrate with a first type of nanoparticles having one or more types of oligonucleotides attached thereto, at least one of the types of oligonucleotides having a sequence complementary to a second portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with said nucleic acid;
• contacting the first type of nanoparticles bound to the substrate with a second type of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on the second type of nanoparticles having a sequence complementary to at least a portion of the sequence of one of the types of oligonucleotides on the first type of nanoparticles, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the first and second types of nanoparticles;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• contacting a nucleic acid to be detected with a substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the substrate with said nucleic acid;
• contacting said nucleic acid bound to the substrate with a type of nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a second portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with said nucleic acid;
• contacting the substrate with silver stain to produce a detectable change;
• and
• observing the detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• contacting a nucleic acid to be detected with a substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the substrate with said nucleic acid;
• contacting said nucleic acid bound to the substrate with liposomes having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the liposomes with said nucleic acid;
• contacting the liposomes bound to the substrate with a first type of nanoparticles having at least a first type oligonucleotides attached thereto, the first type of oligonucleotides having a hydrophobic group attached to the end not attached to the nanoparticles, the contacting taking place under conditions effective to allow attachment of the oligonucleotides on the nanoparticles to the liposomes as a result of hydrophobic interactions;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising

• contacting a nucleic acid to be detected with a substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the substrate with said nucleic acid;
• contacting said nucleic acid bound to the substrate with liposomes having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the liposomes with said nucleic acid;
• contacting the liposomes bound to the substrate with a first type of nanoparticles having at least a first type oligonucleotides attached thereto, the first type of oligonucleotides having a hydrophobic group attached to the end not attached to the nanoparticles, the contacting taking place under conditions effective to allow attachment of the oligonucleotides on the nanoparticles to the liposomes as a result of hydrophobic interactions;
• contacting the first type of nanoparticles bound to the liposomes with a second type of nanoparticles having oligonucleotides attached thereto,
• the first type of nanoparticles having a second type of oligonucleotides attached thereto which have a sequence complementary to at least a portion of the sequence of the oligonucleotides on the second type of nanoparticles,
• the oligonucleotides on the second type of nanoparticles having a sequence complementary to at least a portion of the sequence of the second type of oligonucleotides on the first type of nanoparticles,
• the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the first and second types of nanoparticles;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• providing a substrate having a first type of nanoparticles attached thereto, the nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of a nucleic acid to be detected;
• contacting said nucleic acid with the nanoparticles attached to the substrate under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with said nucleic acid;
• providing an aggregate probe comprising at least two types of nanoparticles having oligonucleotides attached thereto, the nanoparticles of the aggregate probe being bound to each other as a result of the hybridization of some of the oligonucleotides attached to them, at least one of the types of nanoparticles of the aggregate probe having oligonucleotides attached thereto which have a sequence complementary to a second portion of the sequence of said nucleic acid;
• contacting said nucleic acid bound to the substrate with the aggregate probe under conditions effective to allow hybridization of the oligonucleotides on the aggregate probe with said nucleic acid;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• providing a substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of a nucleic acid to be detected;
• providing an aggregate probe comprising at least two types of nanoparticles having oligonucleotides attached thereto, the nanoparticles of the aggregate probe being bound to each other as a result of the hybridization of some of the oligonucleotides attached to them, at least one of the types of nanoparticles of the aggregate probe having oligonucleotides attached thereto which have a sequence complementary to a second portion of the sequence of said nucleic acid;
• contacting said nucleic acid, the substrate and the aggregate probe under conditions effective to allow hybridization of said nucleic acid with the oligonucleotides on the aggregate probe and with the oligonucleotides on the substrate;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• providing a substrate having oligonucleotides attached thereto;
• providing an aggregate probe comprising at least two types of nanoparticles having oligonucleotides attached thereto, the nanoparticles of the aggregate probe being bound to each other as a result of the hybridization of some of the oligonucleotides attached to them, at least one of the types of nanoparticles of the aggregate probe having oligonucleotides attached thereto which have a sequence complementary to a first portion of the sequence of a nucleic acid to be detected;
• providing a type of nanoparticles having at least two types of oligonucleotides attached thereto, the first type of oligonucleotides having a sequence complementary to a second portion of the sequence of said nucleic acid, the second type of oligonucleotides having a sequence complementary to at least a portion of the sequence of the oligonucleotides attached to the substrate;
• contacting said nucleic acid, the aggregate probe, the nanoparticles and the substrate, the contacting taking place under conditions effective to allow hybridization of said nucleic acid with the oligonucleotides on the aggregate probe and on the nanoparticles and hybridization of the oligonucleotides on the nanoparticles with the oligonucleotides on the substrate;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• contacting a nucleic acid to be detected with a substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the substrate with said nucleic acid;
• contacting said nucleic acid bound to the substrate with liposomes having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the liposomes with said nucleic acid;
• providing an aggregate probe comprising at least two types of nanoparticles having oligonucleotides attached thereto, the nanoparticles of the aggregate probe being bound to each other as a result of the hybridization of some of the oligonucleotides attached to them, at least one of the types of nanoparticles of the aggregate probe having oligonucleotides attached thereto which have a hydrophobic group attached to the end not attached to the nanoparticles;
• contacting the liposomes bound to the substrate with the aggregate probe under conditions effective to allow attachment of the oligonucleotides on the aggregate probe to the liposomes as a result of hydrophobic interactions;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• providing a substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of a nucleic acid to be detected;
• providing a core probe comprising at least two types of nanoparticles, each type of nanoparticles having oligonucleotides attached thereto which are complementary to the oligonucleotides on at least one of the other types of nanoparticles, the nanoparticles of the aggregate probe being bound to each other as a result of the hybridization of the oligonucleotides attached to them;
• providing a type of nanoparticles having two types of oligonucleotides attached thereto, the first type of oligonucleotides having a sequence complementary to a second portion of the sequence of said nucleic acid, the second type of oligonucleotides having a sequence complementary to a portion of the sequence of the oligonucleotides attached to at least one of the types of nanoparticles of the core probe;
• contacting said nucleic acid, the nanoparticles, the substrate and the core probe under conditions effective to allow hybridization of said nucleic acid with the oligonucleotides on the nanoparticles and with the oligonucleotides on the substrate and to allow hybridization of the oligonucleotides on the nanoparticles with the oligonucleotides on the core probe;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• providing a substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of a nucleic acid to be detected;
• providing a core probe comprising at least two types of nanoparticles, each type of nanoparticles having oligonucleotides attached thereto which are complementary to the oligonucleotides on at least one other type of nanoparticles, the nanoparticles of the aggregate probe being bound to each other as a result of the hybridization of the oligonucleotides attached to them;
• providing a type of linking oligonucleotides comprising a sequence complementary to a second portion of the sequence of said nucleic acid and a sequence complementary to a portion of the sequence of the oligonucleotides attached to at least one of the types of nanoparticles of the core probe;
• contacting said nucleic acid, the linking oligonucleotides, the substrate and the core probe under conditions effective to allow hybridization of said nucleic acid with the linking oligonucleotides and with the oligonucleotides on the substrate and to allow hybridization of the oligonucleotides on the linking oligonucleotides with the oligonucleotides on the core probe;
• and
• observing a detectable change.

A method of detecting a nucleic acid having at least two portions comprising:

• providing nanoparticles having oligonucleotides attached thereto;
• providing one or more types of binding oligonucleotides, each of the binding oligonucleotides having two portions, the sequence of one portion being complementary to the sequence of one of the portions of the nucleic acid and the sequence of the other portion being complementary to the sequence of the oligonucleotides on the nanoparticles;
• contacting the nanoparticles and the binding oligonucleotides under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with the binding oligonucleotides;
• contacting the nucleic acid and the binding oligonucleotides under conditions effective to allow hybridization of the binding oligonucleotides with the nucleic acid;
• and
• observing a detectable change.

A method of detecting a nucleic acid having at least two portions comprising:

• providing nanoparticles having oligonucleotides attached thereto;
• providing one or more binding oligonucleotides, each of the binding oligonucleotides having two portions, the sequence of one portion being complementary to the sequence of at least two portions of the nucleic acid and the sequence of the other portion being complementary to the sequence of the oligonucleotides on the nanoparticles;
• contacting the nanoparticles and the binding oligonucleotides under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with the binding oligonucleotides;
• contacting the nucleic acid and the binding oligonucleotides under conditions effective to allow hybridization of the binding oligonucleotides with the nucleic acid;
• and
• observing a detectable change.

A method of detecting nucleic acid having at least two portions comprising:

• contacting the nucleic acid with at least two types of particles having oligonucleotides attached thereto,
• the oligonucleotides on the first type of particles having a sequence complementary to a first portion of the sequence of the nucleic acid and being labeled with an energy donor,
• the oligonucleotides on the second type of particles having a sequence complementary to a second portion of the sequence of the nucleic acid and being labeled with an energy acceptor,
• the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the particles with the nucleic acid;
• and
• observing a detectable change brought about by hybridization of the oligonucleotides on the particles with the nucleic acid.

A method of detecting nucleic acid having at least two portions comprising:

• providing a type of microspheres having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of the nucleic acid and being labeled with a fluorescent molecule;
• providing a type of nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a second portion of the sequence of the nucleic acid, nanoparticles being capable of producing a detectable change;
• contacting the nucleic acid with the microspheres and the nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the microspheres and on the nanoparticles with the nucleic acid;
• and
• observing a change in fluorescence, another detectable change produced by the nanoparticles, or both.

A method of detecting nucleic acid having at least two portions comprising:

• providing a first type of metallic or semiconductor nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of the nucleic acid and being labeled with a fluorescent molecule;
• providing a second type of metallic or semiconductor nanoparticles having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a second portion of the sequence of the nucleic acid and being labeled with a fluorescent molecule;
• contacting the nucleic acid with the two types of nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the two types of nanoparticles with the nucleic acid;
• and
• observing changes in fluorescence.

A method of detecting nucleic acid having at least two portions comprising:

• providing a type of particle having oligonucleotides attached thereto, the oligonucleotides having a first portion and a second portion, both portions being complementary to portions of the sequence of the nucleic acid;
• providing a type of probe oligonucleotides comprising a first portion and a second portion, the first portion having a sequence complementary to the first portion of the oligonucleotides attached to the particles and both portions being complementary to portions of the sequence of the nucleic acid, the probe oligonucleotides further being labeled with a reporter molecule at one end;
• contacting the particle and the probe oligonucleotides under conditions effective to allow for hybridization of the oligonucleotides on the particles with the probe oligonucleotides to produce a satellite probe;
• then contacting the satellite probe with the nucleic acid under conditions effective to provide for hybridization of the nucleic acid with the probe oligonucleotides;
• removing the particles;
• and
• detecting the reporter molecule.

A kit comprising at least three containers:

• the first container holding nanoparticles;
• the second container holding a first oligonucleotide having a sequence complementary to the sequence of a first portion of a nucleic acid;
• and
• the third container holding a second oligonucleotide having a sequence complementary to the sequence of a second portion of the nucleic acid.

A kit comprising:

• a substrate having oligonucleotides attached thereto which have a sequence complementary to the sequence of a first portion of a nucleic acid;
• a first container holding nanoparticles having oligonucleotides attached thereto, some of which have a sequence complementary to the sequence of a second portion of the nucleic acid;
• and
• a second container holding nanoparticles having oligonucleotides attached thereto which have a sequence complementary to at least a portion of the sequence of the oligonucleotides attached to the nanoparticles in the first container.

A kit comprising:

• a substrate;
• a first container holding nanoparticles;
• a second container holding a first oligonucleotide having a sequence complementary to the sequence of a first portion of a nucleic acid;
• a third container holding a second oligonucleotide having a sequence complementary to the sequence of a second portion of the nucleic acid;
• and
• a fourth container holding a third oligonucleotide having a sequence complementary to at least a portion of the sequence of the second oligonucleotide.

A kit comprising:

• a substrate having oligonucleotides attached thereto which have a sequence complementary to the sequence of a first portion of a nucleic acid;
• a first container holding liposomes having oligonucleotides attached thereto which have a sequence complementary to the sequence of a second portion of the nucleic acid;
• and
• a second container holding nanoparticles having at least a first type of oligonucleotides attached thereto, the first type of oligonucleotides having a hydrophobic group attached to the end not attached to the nanoparticles.

A kit comprising:

• a substrate having oligonucleotides attached thereto;
• a first container holding an aggregate probe comprising at least two types of nanoparticles having oligonucleotides attached thereto, the nanoparticles of the aggregate probe being bound to each other as a result of the hybridization of some of the oligonucleotides attached to them, at least one of the types of nanoparticles of the aggregate probe having oligonucleotides attached thereto which have a sequence complementary to a first portion of the sequence of the nucleic acid;
• and
• a second container holding nanoparticles having at least two types of oligonucleotides attached thereto, the first type of oligonucleotides having a sequence complementary to a second portion of the sequence of the nucleic acid, and the second type of oligonucleotides having a sequence complementary to at least a portion of the sequence of the oligonucleotides attached to the substrate.

A kit comprising:

• a substrate, the substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to the sequence of a first portion of a nucleic acid;
• a first container holding liposomes having oligonucleotides attached thereto which have a sequence complementary to the sequence of a second portion of the nucleic acid;
• and
• a second container holding an aggregate probe comprising at least two types of nanoparticles having oligonucleotides attached thereto, the nanoparticles of the aggregate probe being bound to each other as a result of the hybridization of some of the oligonucleotides attached to them, at least one of the types of nanoparticles of the aggregate probe having oligonucleotides attached thereto which have a hydrophobic group attached to the end not attached to the nanoparticles.

A kit comprising at least three containers:

• the first container holding nanoparticles;
• the second container holding a first oligonucleotide having a sequence complementary to the sequence of a first portion of a nucleic acid;
• and
• the third container holding a second oligonucleotide having a sequence complementary to the sequence of a second portion of the nucleic acid.

A kit comprising:

• a substrate having oligonucleotides attached thereto which have a sequence complementary to the sequence of a first portion of a nucleic acid;
• a first container holding nanoparticles having oligonucleotides attached thereto, some of which have a sequence complementary to the sequence of a second portion of the nucleic acid;
• and
• a second container holding nanoparticles having oligonucleotides attached thereto which have a sequence complementary to at least a portion of the sequence of the oligonucleotides attached to the nanoparticles in the first container.

A kit comprising:

• a substrate;
• a first container holding nanoparticles;
• a second container holding a first oligonucleotide having a sequence complementary to the sequence of a first portion of a nucleic acid;
• a third container holding a second oligonucleotide having a sequence complementary to the sequence of a second portion of the nucleic acid;
• and
• a fourth container holding a third oligonucleotide having a sequence complementary to at least a portion of the sequence of the second oligonucleotide.

A kit comprising:

• a substrate having oligonucleotides attached thereto which have a sequence complementary to the sequence of a first portion of a nucleic acid;
• a first container holding liposomes having oligonucleotides attached thereto which have a sequence complementary to the sequence of a second portion of the nucleic acid;
• and
• a second container holding nanoparticles having at least a first type of oligonucleotides attached thereto, the first type of oligonucleotides having a hydrophobic group attached to the end not attached to the nanoparticles.

A method of nanofabrication comprising

• providing at least one type of linking oligonucleotide having a selected sequence, the sequence of each type of linking oligonucleotide having at least two portions;
• providing one or more types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on each of the types of nanoparticles having a sequence complementary to the sequence of a portion of a linking oligonucleotide;
• and
• contacting the linking oligonucleotides and nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles to the linking oligonucleotides so that a desired nanomaterial or nanostructure is formed wherein the nanoparticles are held together by oligonucleotide connectors.

A method of nanofabrication comprising:

• providing at least two types of nanoparticles having oligonucleotides attached thereto,
• the oligonucleotides on the first type of nanoparticles having a sequence complementary to that of the oligonucleotides on the second of the nanoparticles;
• the oligonucleotides on the second type of nanoparticles having a sequence complementary to that of the oligonucleotides on the first type of nanoparticles;
• and
• contacting the first and second types of nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles to each other so that a desired nanomaterial or nanostructure is formed.

An assembly of containers comprising:

• a first container holding nanoparticles having oligonucleotides attached thereto, and
• a second container holding nanoparticles having oligonucleotides attached thereto,
• the oligonucleotides attached to the nanoparticles in the first container having a sequence complementary to that of the oligonucleotides attached to the nanoparticles in the second container,
• the oligonucleotides attached to the nanoparticles in the second container having a sequence complementary to that of the oligonucleotides attached to the nanoparticles in the second container.

A method of binding oligonucleotides to charged nanoparticles to produce stable nanoparticle-oligonucleotide conjugates, the method comprising:

• providing oligonucleotides having covalently bound thereto a moiety comprising a functional group which can bind to the nanoparticles;
• contacting the oligonucleotides and the nanoparticles in water for a period of time sufficient to allow at least some of the oligonucleotides to bind to the nanoparticles;
• adding at least one salt to the water to form a salt solution, the ionic strength of the salt solution being sufficient to overcome at least partially the electrostatic attraction or repulsion of the oligonucleotides for the nanoparticles and the electrostatic repulsion of the oligonucleotides for each other;
• and
• contacting the oligonucleotides and nanoparticles in the salt solution for an additional period of time sufficient to allow sufficient additional oligonucleotides to bind to the nanoparticles to produce the stable nanoparticle-oligonucleotide conjugates.

A method of binding oligonucleotides to nanoparticles to produce nanoparticle-oligonucleotide conjugates, the method comprising:

• providing oligonucleotides, the oligonucleotides comprising:
• a type of recognition oligonucleotides;
• and
• a type of diluent oligonucleotides;
• contacting the oligonucleotides with the nanoparticles under conditions effective to allow at least some of each of the types of oligonucleotides to bind to the nanoparticles to produce the nanoparticle-oligonucleotide conjugates.

A method of binding oligonucleotides to charged nanoparticles to produce nanoparticle-oligonucleotide conjugates, the method comprising:

• providing oligonucleotides having covalently bound thereto a moiety comprising a functional group which can bind to the nanoparticles, the oligonucleotides comprising:
• a type of recognition oligonucleotides;
• and
• a type of diluent oligonucleotides;
• contacting the oligonucleotides with the nanoparticles in water for a period of time sufficient to allow at least some of each of the types of oligonucleotides to bind to the nanoparticles;
• adding at least one salt to the water to form a salt solution, the ionic strength of the salt solution being sufficient to overcome at least partially the electrostatic attraction or repulsion of the oligonucleotides for the nanoparticles and the electrostatic repulsion of the oligonucleotides for each other;
• and
• contacting the oligonucleotides and nanoparticles in the salt solution for an additional period of time sufficient to allow additional oligonucleotides of each of the types of oligonucleotides to bind to the nanoparticles to produce the nanoparticle- oligonucleotide conjugates.

A method of detecting a nucleic acid having at least two portions comprising:

• (a) contacting the nucleic acid with a substrate having oligonucleotides attached thereto, the oligonucleotides being located between a pair of electrodes, the oligonucleotides having a sequence complementary to a first portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the substrate with said nucleic acid;
• (b) contacting said nucleic acid bound to the substrate with a first type of nanoparticles, the nanoparticles being made of a material which can conduct electricity, the nanoparticles having one or more types of oligonucleotides attached thereto, at least one of the types of oligonucleotides having a sequence complementary to a second portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with said nucleic acid;
• and
• (c) detecting a change in conductivity.

A method of detecting nucleic acid having at least two portions comprising:

• (a) contacting a nucleic acid with a substrate having oligonucleotides attached thereto, the oligonucleotides being located between a pair of electrodes, the oligonucleotides having a sequence complementary to a first portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the substrate with said nucleic acid;
• (b) contacting said nucleic acid bound to the substrate with an aggregate probe having oligonucleotides attached thereto, at least one of the types of oligonucleotides on the aggregate probe comprising a sequence complementary to the sequence of a second portion of said nucleic acid, the nanoparticles of the aggregate probe being made of a material which can conduct electricity, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the aggregate probe with the nucleic acid;
• and
• (c) detecting a change in conductivity.

A method of binding oligonucleotides to charged nanoparticles to produce nanoparticle-oligonucleotide conjugates, the method comprising:

• providing oligonucleotides having covalently bound cyclic disulfide function groups that can bind to nanoparticles, the oligonucleotides comprising:
• a type of recognition oligonucleotides;
• and
• a type of diluent oligonucleotides;
• contacting the oligonucleotides with the nanoparticles in water for a period of time sufficient to allow at least some of each of the types of oligonucleotides to bind to the nanoparticles;
• adding at least one salt to the water to form a salt solution, the ionic strength of the salt solution being sufficient to overcome at least partially the electrostatic attraction or repulsion of the oligonucleotides for the nanoparticles and the electrostatic repulsion of the oligonucleotides for each other;
• and
• contacting the oligonucleotides and nanoparticles in the salt solution for an additional period of time sufficient to allow additional oligonucleotides of each of the types of oligonucleotides to bind to the nanoparticles to produce the nanoparticle- oligonucleotide conjugates.

A method of binding oligonucleotides to charged nanoparticles to produce nanoparticle-oligonucleotide conjugates, the method comprising:

• providing oligonucleotides having covalently bound polythiol function groups that can bind to nanoparticles, the oligonucleotides comprising:
• a type of recognition oligonucleotides;
• and
• a type of diluent oligonucleotides;
• contacting the oligonucleotides with the nanoparticles in water for a period of time sufficient to allow at least some of each of the types of oligonucleotides to bind to the nanoparticles;
• adding at least one salt to the water to form a salt solution, the ionic strength of the salt solution being sufficient to overcome at least partially the electrostatic attraction or repulsion of the oligonucleotides for the nanoparticles and the electrostatic repulsion of the oligonucleotides for each other;
• and
• contacting the oligonucleotides and nanoparticles in the salt solution for an additional period of time sufficient to allow additional oligonucleotides of each of the types of oligonucleotides to bind to the nanoparticles to produce the nanoparticle-oligonucleotide conjugates.

A method for detecting an analyte in a sample comprising:

• providing a type of nanoparticle conjugate having oligonucleotides bound thereto, at least a portion of the oligonucleotides attached to the nanoparticles are bound, as a result of hybridization, to second oligonucleotides having a specific binding complement of said analyte bound thereto;
• contacting the analyte with the nanoparticle conjugate under conditions effective to allow specific binding interactions between the analyte and specific binding complement bound to the nanoparticle conjugate;
• and
• observing a detectable change brought about by the specific binding interaction of the analyte and the specific binding complement of said analyte.

A method for detecting an analyte comprising:

• providing a type of nanoparticle conjugate having oligonucleotides bound thereto, at least a portion of the oligonucleotides attached to the nanoparticles are bound, as a result of hybridization, to a first portion of a linker oligonucleotide, the linker oligonucleotide having a second portion that is bound, as a result of hybridization, to oligonucleotides having bound thereto a specific binding complement of said analyte;
• contacting the analyte with a nanoparticle conjugate under conditions effective to allow specific binding interaction between the analyte and specific binding complement bound to the nanoparticle conjugate;
• and
• observing a detectable change brought about by the specific binding interaction of the analyte and the specific binding complement of said analyte.

A method for detecting an analyte comprising:

• providing (i) an analyte having an oligonucleotide bound thereto, (ii) a first type of nanoparticles having oligonucleotides bound thereto, the oligonucleotides bound to the first type of nanoparticles having a sequence that is complementary to the sequence of the oligonucleotide bound to the analyte, and (iii) a second type of nanoparticle conjugate having oligonucleotides bound thereto, a portion of the oligonucleotides bound to the second type of nanoparticle are bound, as a result of hybridization, to oligonucleotides having bound thereto a specific binding complement of said analyte;
• contacting the oligonucleotide bound to the analyte with the first type of nanoparticles under conditions effective to allow hybridization between the oligonucleotides bound to the analyte with the oligonucleotides attached to the first type of nanoparticles to form a nanoparticle analyte conjugate;
• contacting the nanoparticle analyte conjugate with a second type of nanoparticle conjugates under conditions effective to allow specific binding interaction between the analyte and specific binding complement of the second type of nanoparticle conjugate;
• and
• observing a detectable change brought about by the specific binding interaction of the analyte and the specific binding complement of said analyte.

A method for detecting an analyte comprising:

• providing (ii) a linker oligonucleotide, the linker oligonucleotide having at least two portions, (iii) a first type of nanoparticle have oligonucleotides attached thereto, a least a portion of the oligonucleotides bound to the first type of nanoparticles have a sequence that is complementary to a second portion of the linker oligonucleotide;
• (i) an analyte having an oligonucleotide bound thereto, the oligonucleotide having a sequence complementary to the first portion of the linker oligonucleotide;
• and (iv) a second type of nanoparticles having oligonucleotides bound thereto, at least a portion of the oligonucleotides bound to the second type of nanoparticles are bound, as a result of hybridization, to an oligonucleotide having bound thereto a specific binding complement of the analyte;
• contacting the linker oligonucleotide with the first type of nanoparticles under conditions effective to allow hybridization between the oligonucleotide attached to the first type of nanoparticles with a first portion of the linker oligonucleotide;
• contacting the linker oligonucleotide with the oligonucleotide having the analyte bound thereto under conditions effective to allow hybridization between the oligonucleotide having analyte bound thereto with a second portion of the linker oligonucleotide;
• contacting the analyte bound to the first type of nanoparticles with a second type of nanoparticles under conditions effective to allow specific binding interactions between the analyte bound to the first type of nanoparticles and the specific binding complement bound to the second type of nanoparticles;
• and
• observing the detectable change brought about by the specific binding of the analyte to the specific binding complement of the analyte.

A method for detecting an analyte comprising:

• providing (i) a support having an analyte bound thereto and (ii) a nanoparticle conjugate having oligonucleotides bound thereto, a least a portion of the oligonucleotides are bound, as a result of hybridization, to second oligonucleotides having a specific binding complement of said analyte;
• contacting the analyte bound to the support to the nanoparticle conjugate under conditions effective to allow specific binding interactions between the analyte and specific binding complement bound to the nanoparticle conjugate;
• and
• observing a detectable change dependent on the specific binding of the analyte to the specific binding complement of the analyte.

A method for detecting an analyte comprising:

• providing (i) a support having a oligonucleotides bound thereto, (ii) an analyte having an oligonucleotide bound thereto, the oligonucleotide bound to the analyte has a sequence that is complementary to the oligonucleotides bound to the support;
• and (iii) a type of nanoparticle conjugate having oligonucleotides bound thereto, at least a portion of the oligonucleotides bound to the nanoparticle are bound, as a result of hybridization, to second oligonucleotides having bound thereto a specific binding complement of said analyte;
• contacting the oligonucleotides bound to the support with the olignonucleotide bound to the analyte under conditions effective to allow hybridization between the oligonucleotides bound to the support and the oligonucleotides bound to the analytes;
• contacting the analyte bound to the support with the nanoparticle conjugate under conditions effective to allow for specific binding interactions between the analyte bound to the support and the specific binding complement bound to the nanoparticle;
• and
• observing a detectable change dependent on the specific binding of the analyte to the specific binding complement of the analyte.

A method for detecting an analyte in a sample comprising:

• providing (i) a support having oligonucleotides bound thereto, (ii) a linker oligonucleotide, (ii) an analyte having an oligonucleotide bound thereto,(iii) a type of nanoparticle conjugate having oligonucleotides bound thereto, wherein at least a portion of the oligonucleotides bound to the nanoparticle conjugate are bound, as a result of hybridization, to oligonucleotides having bound thereto a specific binding complement of said analyte, the sequence of the linker oligonucleotide having at least two portions, the oligonucleotides bound to the support have a sequence that is complementary to the first portion of the linker oligonucleotide, the oligonucleotide bound to the analyte has a sequence that is complementary to the second portion of the linker oligonucleotides;
• contacting the linker oligonucleotide with the oligonucleotide bound to the support under conditions effective to allow hybridization between the oligonucleotides bound to the support with the first portion of the linker oligonucleotide;
• contacting the linker oligonucleotide with the oligonucleotide bound to the analyte under conditions effective to allow hybridization between the oligonucleotide bound to the analyte and the second portion of the linker oligonucleotide;
• contacting analyte bound to the support with the nanoparticle conjugate under conditions effective to allow specific binding interaction between the analyte bound to the support and the specific binding complement bound to the nanoparticle conjugate;
• and
• observing a detectable change dependent on the specific binding of the analyte to the specific binding complement of the analyte.

A method for detecting an analyte comprising:

• providing (i) a support having oligonucleotides bound thereto, (ii) an analyte having oligonucleotides bound thereto, the sequence of the oligonucleotide bound to the analyte is complementary to the sequence of the oligonucleotides bound the support;
• (iii) a type of nanoparticles having oligonucleotides bound thereto, at least a portion of the oligonucleotides attached to the nanoparticle are bound, as a result of hybridization, to a first portion of a linker oligonucleotide, a second portion of the linker oligonucleotide is further bound, as a result of hybridization, to an oligonucleotide having a oligonucleotide having bound thereto a specific binding complement of said analyte;
• contacting the oligonucleotides bound to the support with oligonucleotide bound to an analyte under conditions effective to allow hybridization between the oligonucleotides bound to the support with the oligonucleotides bound to the analyte;
• contacting the analyte bound to the support with the the nanoparticle conjugate under conditions effective to allow specific binding interactions between the analyte bound to the support and the specific binding complement bound to the nanoparticle;
• and
• observing a detectable change dependent on the specific binding of the analyte to the specific binding complement of the analyte.

A method for detecting an analyte comprising:

• providing (i) a support having an analyte bound thereto, (ii) an aggregate probe comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them, and at least one of the types of nanoparticles of the aggregate probe have oligonucleotides attached thereto which are bound, as a result of hybridization, to second oligonucleotides having bound thereto a specific binding complement of said analyte;
• contacting the support with the aggregate probe under conditions effective to allow specific binding interactions between the analyte bound to the support and specific binding complement bound to the aggregate probe;
• and
• observing a detectable change dependent on the specific binding of the analyte to the specific binding complement of the analyte.

A method for detecting an analyte comprising:

• providing (i) a support having an oligonucleotide bound thereto;
• (ii) an analyte having an oligonucleotide bound thereto, the oligonucleotide bound to the analyte has a sequence that is complementary to the sequence of the oligonucleotides bound to the support, (iii) an aggregate probe comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them, and at least one of the types of nanoparticles of the aggregate probe have oligonucleotides attached thereto which are bound, as a result of hybridization, to second oligonucleotides having bound thereto a specific binding complement of said analyte;
• contacting a support having oligonucleotides bound thereto with the analyte having an oligonucleotide bound thereto. The contacting occurs under conditions effective to allow hybridization of the oligonucleotides bound to the analyte with the oligonucleotides bound to the support;
• and
• contacting the analyte bound to the support with an aggregate probe under conditions effective to allow specific binding interactions between the analyte bound to the support and specific binding complement bound to the aggregate probe;
• and
• observing a detectable change dependent on the specific binding of the analyte to the specific binding complement of the analyte.

A method for detecting an analyte comprising:

• providing (i) a support having a oligonucleotides bound thereto, (ii) a linker oligonucleotide having at least two portions,(iii) an analyte having oligonucleotides bound thereto, (iv) an aggregate probe comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them, at least one of the types of nanoparticles of the aggregate probe have some oligonucleotides attached thereto which bound, as a result of hybridization, to second oligonucleotides having bound thereto a specific binding complement of said analyte, the oligonucleotides bound to the support has a sequence that is complementary to a first portion of the linker oligonucleotide, the oligonucleotide bound to the analyte has a sequence that is complementary with the second portion of the linker oligonucleotide;
• contacting the linker oligonucleotide with the oligonucleotides bound to the support under conditions effective to allow hybridization between the oligonucleotides bound to the support and the first portion of the linker oligonucleotide;
• contacting the linker oligonucleotide with the oligonucleotide bound to the analyte under conditions effective to allow hybridization between the second portion of the linker oligonucleotide bound to the support and the oligonucleotide bound to the analyte;
• contacting the analyte bound to the support with the aggregate probe under conditions effective to allow specific binding interactions between the analyte bound to the support and specific binding complement bound to the aggregate probe;
• and
• observing a detectable change dependent on the specific binding of the analyte to the specific binding complement of the analyte.

A method for detecting an analyte comprising:

• providing (i) a support having oligonucleotides bound thereto, (ii) an analyte having oligonucleotide bound thereto, the oligonucleotide has a sequence that is complementary to the sequence of the oligonucleotides bound to the support, (iii) an aggregate probe comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them and at least one of the types of nanoparticles of the aggregate probe have some oligonucleotides attached thereto which bound to a first portion of a linker oligonucleotide as a result of hybridization, a second portion of the second linker oligonucleotide is bound, as a result of hybridization, to a oligonucleotide having bound thereto a specific binding complement of said analyte;
• contacting a support having oligonucleotides bound thereto with an oligonucleotide having analyte bound thereto under conditions effective to allow hybridization of the oligonucleotides bound to the analyte with the oligonucleotides bound to the support;
• contacting the analyte bound to the support with the aggregate probe under conditions effective to allow specific binding interactions between the analyte bound to the support and the specific binding complement bound to the aggregate probe;
• and
• observing a detectable change dependent on the specific binding of the analyte to the specific binding complement of the analyte.

A method for detecting an analyte comprising:

• providing (i) a support having an analyte bound thereto and (ii) a nanoparticle conjugate having oligonucleotides bound thereto, at least some of the oligonucleotides attached to the nanoparticle are bound, as a result of hybridization, to second oligonucleotides having bound thereto a specific binding complement of said analyte;
• contacting a support having an analyte bound thereto with the nanoparticle conjugate under conditions effective to allow specific binding interactions between the analyte bound to the support and specific binding complement bound to the nanoparticle conjugate;
• contacting the nanoparticle conjugate bound to the support with silver stain to produce a detectable change;
• and
• observing the detectable change dependent on the specific binding of the analyte and the specific binding complement of the analyte.

A method for detecting a polyvalent analyte comprising:

• providing a nanoparticle probe having oligonucleotides bound thereto, at least some of the oligonucleotides attached to the nanoparticle are bound to a first portion of a reporter oligonucleotide as a result of hybridization, a second portion of the reporter oligonucleotide is bound, as a result of hybridization, to an oligonucleotide having bound thereto a specific binding complement of the analyte;
• contacting a polyvalent analyte with the nanoparticle probe under conditions effective to allow specific binding interactions between the analyte and the nanoparticle probe and to form an aggregated complex;
• isolating the aggregated complex;
• subjecting the aggregated complex to conditions effective to dehybridize the aggregated complex and to release the reporter oligonucleotide;
• and
• detecting for the presence of reporter oligonucleotide.

A method for detecting a nucleic acid comprising:

• to providing (i) one or more types of nanoparticles having oligonucleotides bound thereto, the oligonucleotides bound to the nanoparticles have a sequence that is complementary to a first portion of the nucleic acid and (ii) a complex comprising streptavidin or avidin bound, by specific binding interaction, to two or more biotin molecules each having oligonucleotides bound thereto, the oligonucleotides bound to biotin have a sequence that is complementary to a second portion of the nucleic acid;
• contacting the nucleic acid, nanoparticle conjugate and complex under conditions effective to allow hybridization of the first portion of the nucleic acid with the oligonucleotides bound to the nanoparticles and the second portion of the nucleic acid with the oligonucleotides bound to the complex;
• and
• observing the detectable change resulting from the hybridization of the nanoparticles, the complex and the nucleic acid.

A method for detecting a nucleic acid comprising:

• providing (i) one or more types of nanoparticles having oligonucleotides bound thereto, the oligonucleotides bound to the nanoparticles have a sequence that is complementary to a first portion of the nucleic acid, (ii) oligonucleotides having biotin bound thereto;
• the oligonucleotide bound to the biotins have a sequence that is complementary to a second portion of the nucleic acid, and (iii) streptavidin or avidin;
• contacting the nucleic acid with the nanoparticle conjugate and oligonucleotide bound to biotin under conditions effective to allow hybridization between the first portion of the nucleic acid with the oligonucleotides attached to the nanoparticles and the second portion of the nucleic acid with the oligonucleotides attached to the biotin to form a complex;
• contacting the complex with streptavidin or avidin under conditions effective to allow specific binding interaction between the biotin bound to the complex with streptavidin or avidin;
• and
• observing the detectable change resulting from the specific binding of biotin bound to the complex with streptavidin or avidin.

A method for detecting a nucleic acid comprising:

• providing a first type of nanoparticle conjugate having oligonucleotides attached thereto, at least some of the oligonucleotides attached to the nanoparticles have a sequence that is complementary to a first portion of the nucleic acid;
• contacting the nucleic acid with a first type of nanoparticle under conditions effective to allow hybridization between the oligonucleotides attached to the nanoparticle and the first portion of the nucleic acid;
• providing an oligonucleotide having a sbp member bound thereto is provided, the oligonucleotide bound to the sbp member has a sequence that is complementary to the second portion of the sequence of the nucleic acid;
• contacting the nucleic acid bound to the first type of nanoparticle under conditions effective to allow hybridization between the oligonucleotide bound to the sbp member and the second portion of the nucleic acid;
• providing a second type of nanoparticle conjugate having oligonucleotides bound thereto is provided, at least a portion of the oligonucleotides bound to the second type of nanoparticle are bound, as a result of hybridization, to oligonucleotides having bound thereto a specific binding complement of said analyte;
• contacting the nucleic acid bound to the first type of nanoparticle and the oligonucleotide bound to the sbp member with the oligonucleotides bound to the second type of nanoparticles under conditions effective to allow specific binding interaction between the sbp member bound to the first type of nanoparticle and the sbp complement bound to the second type of nanoparticle;
• and
• observing the detectable change resulting from the specific binding of biotin with streptavidin or avidin.

A method for detecting a nucleic acid comprising:

• providing a support having oligonucleotides bound thereto, the oligonucleotides bound to the support have a sequence that is complementary to the first portion of the nucleic acid;
• contacting the nucleic acid with a support having oligonucleotides bound thereto under conditions effective to allow hybridization between the oligonucleotides bound to the support with the first portion of the nucleic acid;
• providing an oligonucleotide having a sbp member bound thereto, the oligonucleotide bound to the sbp member has a sequence that is complementary to the second portion of the nucleic acid;
• contacting the nucleic acid bound to the support with the oligonucleotide bound to the sbp member under conditions effective to allow hybridization between the oligonucleotide bound to the sbp member and the second portion of the nucleic acid;
• providing a type of nanoparticle conjugate having oligonucleotides bound thereto, at least a portion of the oligonucleotides bound to the nanoparticle conjugate are bound, as a result of hybridization, to oligonucleotides having bound thereto a specific binding complement of said sbp member;
• contacting the sbp member bound to the support with the nanoparticle conjugate under conditions effective to allow specific binding interaction between the sbp member bound to the support and the specific binding complement bound to the nanoparticle;
• and
• observing a detectable change dependent on the specific binding of the sbp member and the specific binding complement.

A method for detecting a nucleic acid comprising:

• providing a nanoparticle conjugate having oligonucleotides attached thereto, at least some of the oligonucleotides attached to the nanoparticles have a sequence that is complementary to the first portion of the nucleic acid;
• contacting a nucleic acid with the oligonucleotides bound to the nanoparticle conjugate under conditions effective to allow hybridization of the oligonucleotides bound to the nanoparticles with the first portion of the nucleic acid;
• providing an oligonucleotide having sbp member bound thereto, the oligonucleotide bound to the sbp member has a sequence that is complementary to the second portion of the nucleic acid;
• contacting the nucleic acid with the oligonucleotide having the sbp member under conditions effective to allow hybridization between the oligonucleotide having the sbp member and the nucleic acid;
• providing a support having bound thereto a specific binding complement of the sbp member;
• contacting the support with the sbp member bound to the nanoparticle under conditions effective to allow specific binding interactions to occur between the sbp member and the sb complement bound to the support;
• and
• observing a detectable event dependent on the specific binding of the sbp member and the sb complement of the sbp member.

A method for detecting a nucleic acid comprising:

• providing a support having oligonucleotides bound thereto, the oligonucleotides bound the support have a sequence that is complementary to a first portion of the nucleic acid;
• contacting the nucleic acid with the support under conditions effective to allow hybridization between the oligonucleotides bound to the support and the first portion of the nucleic acid;
• providing an oligonucleotide having a sbp member bound thereto, the oligonucleotide bound to the sbp member has a sequence that is complementary with the second portion of the nucleic acid;
• contacting the nucleic acid bound to the support with the oligonucleotide bound to the sbp member under conditions effective to allow hybridization between the second portion of the nucleic acid bound to the support and the oligonucleotide bound to the sbp member;
• providing an aggregate probe comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them and at least one of the types of nanoparticles of the aggregate probe have some oligonucleotides attached thereto which bound, as a result of hybridization, to oligonucleotides having bound thereto a specific binding complement of said sbp member;
• contacting the sbp member bound to the support with the aggregate probe under conditions effective to allow specific binding interactions between the sbp member bound to the support and specific binding complement bound to the aggregate probe;
• and
• observing a detectable change dependent on the specific binding of the sbp member and the sb complement of the sbp member.

A method for detecting a nucleic acid comprising:

• providing (i) an aggregate probe comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them and at least one of the types of nanoparticles of the aggregate probe have some oligonucleotides attached thereto which are complementary to a first portion of the nucleic acid, and (ii) an oligonucleotide having sbp member, the oligonucleotide having an sbp member bound thereto has a sequence that is complementary to the second portion of the nucleic acid;
• contacting the nucleic acid with an aggregate probe under conditions effective to allow hybridization between a portion of the oligonucleotides bound to the aggregate probe with the first portion of the nucleic acid under conditions effective to allow hybridization between the oligonucleotides bound to the aggregate probe with the first portion of the nucleic acid;
• contacting the nucleic acid with an oligonucleotide having sbp member, the oligonucleotide having an sbp member bound thereto has a sequence that is complementary to the second portion of the nucleic acid under conditions effective to allow hybridization between the oligonucleotides bound the the sbp members with the second portion of the nucleic acid;
• providing a support having bound thereto a specific binding complement of the sbp member;
• contacting the specific binding complement bound to the support with the sbp member bound to the aggregate probe under conditions effective to allow specific binding interactions to occur between the sbp member bound to the aggregate probe and the sb complement bound to the support;
• and
• observing a detectable event dependent on the specific binding of the sbp member and the sb complement.

A nanoparticle conjugate for detecting an analyte comprising:

• (i) nanoparticles having oligonucleotides bound thereto;
• (ii) oligonucleotide having bound thereto a specific binding complement of an analyte member;
• and
• (iii) a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is bound, as a result of hybridization, to the oligonucleotides bound to the nanoparticle and a second portion of the linker oligonucleotide is bound, as a result of hybridization, to the oligonucleotides having bound thereto a specific binding complement of an analyte.

An aggregate probe for detecting an analyte comprising:

• (i) at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• (ii) oligonucleotides having bound thereto a specific binding complement of an analyte;
• and
• (iii) a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is bound, as a result of hybridization, to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe;
• and a second portion of the linker oligonucleotide is bound, as a result of hybridization, to the oligonucleotides having bound thereto a specific binding complement of an analyte.

A kit for detecting an analyte comprising

• (a) at least one container holding nanoparticle conjugates comprising (i) nanoparticles having oligonucleotides bound thereto;
• and (ii) oligonucleotide having bound thereto a specific binding complement of an analyte, the oligonucleotides having the specific binding pair member have a sequence that is complementary to at least a portion of the oligonucleotides bound to the nanoparticles and are bound, as a result of hybridization, to at least a portion of the oligonucleotides bound to the nanoparticles;
• and
• (b) an optional support for observing a detectable change.

A kit for detecting an analyte comprising

• (a) at least one container holding nanoparticle conjugates comprising
• (i) nanoparticles having oligonucleotides bound thereto;
• (ii) oligonucleotide having bound thereto a specific binding complement of an analyte member;
• and
• (iii) a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is bound, as a result of hybridization, to the oligonucleotides bound to the nanoparticle and a second portion of the linker oligonucleotide is bound, as a result of hybridization, to the oligonucleotides having bound thereto a specific binding complement of an analyte;
• and
• (b) an optional support for observing a detectable change.

A kit for detecting an analyte comprising

• (b) at least one container holding aggregate probes comprising
• (i) at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• and
• (ii) oligonucleotides having bound thereto a specific binding complement of an analyte, the oligonucleotides having the specific binding complement bound thereto are bound, as a result of hybridization, to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe;
• and
• (b) an optional support for observing a detectable change.

A kit for detecting an analyte comprising

• (a) at least one container holding aggregate probes comprising
• (i) at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• (ii) oligonucleotides having bound thereto a specific binding complement of an analyte;
• and
• (iii) a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is bound, as a result of hybridization, to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe;
• and a second portion of the linker oligonucleotide is bound, as a result of hybridization, to the oligonucleotides having bound thereto a specific binding complement of an analyte;
• and
• (b) an optional support for observing a detectable change.

A kit for detecting an analyte comprising:

• (a) at least one container holding a type of nanoparticle conjugates comprising nanoparticles having oligonucleotides bound thereto;
• (b) a container holding oligonucleotide having bound thereto a specific binding complement of an analyte, the oligonucleotides having bound thereto the specific binding pair member have a sequence that is complementary to at least a portion of the oligonucleotides bound to the nanoparticles;
• and
• (c) an optional support for observing a detectable change.

A kit for detecting an analyte comprising

• (a) at least one container holding nanoparticle conjugates comprising nanoparticles having oligonucleotides bound thereto;
• (b) a container holding oligonucleotide having bound thereto a specific binding complement of an analyte member;
• (c) a container holding a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is complementary to at least a portion of the oligonucleotides bound to the nanoparticle and a second portion of the linker oligonucleotide is complementary to the oligonucleotides having bound thereto a specific binding complement of an analyte;
• and
• (d) an optional support for observing a detectable change.

A kit for detecting an analyte comprising

• (a) at least one container holding aggregate probes comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• (b) a container holding oligonucleotides having bound thereto a specific binding complement of an analyte, the oligonucleotides having bound thereto the specific binding complement are complementary to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe;
• and
• (c) an optional support for observing a detectable change.

A kit for detecting an analyte comprising

• (a) at least one container holding aggregate probes comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• (b) a container holding oligonucleotides having bound thereto a specific binding complement of an analyte;
• (c) a container holding a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide has a sequence that is complementary to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe;
• and a second portion of the linker oligonucleotide has a sequence that is complementary to the oligonucleotides having bound thereto a specific binding complement of an analyte;
• and
• (d) an optional support for observing a detectable change.

A kit for detecting an analyte comprising:

• (a) at least one container holding a type of nanoparticle conjugates comprising nanoparticles having oligonucleotides bound thereto;
• (b) a container holding oligonucleotide having covalently bound thereto a functional group for binding a specific binding complement of an analyte, the oligonucleotides having the bound functional group have a sequence that is complementary to at least a portion of the oligonucleotides bound to the nanoparticles;
• and
• (c) an optional support for observing a detectable change.

A kit for detecting an analyte comprising

• (a) at least one container holding nanoparticle conjugates comprising nanoparticles having oligonucleotides bound thereto;
• (b) a container holding oligonucleotide having covalently bound thereto a functional group for binding a specific binding complement of an analyte;
• (c) a container holding a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is complementary to at least a portion of the oligonucleotides bound to the nanoparticle and a second portion of the linker oligonucleotide is complementary to the oligonucleotides having the bound functional group;
• and
• (d) an optional support for observing a detectable change.

A kit for detecting an analyte comprising

• (a) at least one container holding aggregate probes comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• (b) a container holding oligonucleotide having covalently bound thereto a functional group for binding a specific binding complement of an analyte, the oligonucleotides having the functional group have a sequence that is complementary to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe;
• and
• (c) an optional support for observing a detectable change.

A kit for detecting an analyte comprising

• (a) at least one container holding aggregate probes comprising at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• (b) a container holding oligonucleotide having covalently bound thereto a functional group for binding a specific binding complement of an analyte;
• (c) a container holding a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide has a sequence that is complementary to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe;
• and a second portion of the linker oligonucleotide has a sequence that is complementary to the oligonucleotides having the functional group bound thereto;
• and
• (d) an optional support for observing a detectable change.

A kit for detecting an analyte comprising:

• a substrate having oligonucleotides attached thereto;
• an oligonucleotide having a covalently bound thereto a functional group for binding a specific binding complement of an analyte, the oligonucleotide bound to the functional group having a sequence that is complementary to the oligonucleotides bound to the substrate;
• and
• a nanoparticle conjugate comprising (i) nanoparticles having oligonucleotides bound thereto;
• and (ii) oligonucleotide having bound thereto a specific binding complement of an analyte, the oligonucleotides having bound thereto the specific binding complement have a sequence that is complementary to at least a portion of the oligonucleotides bound to the nanoparticles and are bound, as a result of hybridization, to at least a portion of the oligonucleotides bound to the nanoparticles.

A kit for detecting an analyte comprising:

• a substrate having oligonucleotides attached thereto;
• an oligonucleotide having a covalently bound thereto a functional group for binding a specific binding complement of an analyte, the oligonucleotide bound to the functional group having a sequence that is complementary to the oligonucleotides bound to the substrate;
• and
• nanoparticle conjugates comprising (i) nanoparticles having oligonucleotides bound thereto;
• (ii) oligonucleotide having bound thereto a specific binding complement of the sbp member;
• and (iii) a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is bound, as a result of hybridization, to the oligonucleotides bound to the nanoparticle and a second portion of the linker oligonucleotide is bound, as a result of hybridization, to the oligonucleotides having bound thereto a specific binding complement of an analyte.

A kit for detecting a nucleic acid comprising:

• a substrate having oligonucleotides attached thereto, the oligonucleotides bound to the substate have a sequence that is complementary to a first portion of the nucleic acid;
• an oligonucleotide having an sbp member bound thereto, the oligonucleotide having a sequence that is complementary to a second portion of the nucleic acid;
• and
• a nanoparticle conjugate comprising (i) nanoparticles having oligonucleotides bound thereto;
• and (ii) oligonucleotide having bound thereto a specific binding complement of an sbp member, the oligonucleotides having bound thereto the specific binding complement have a sequence that is complementary to at least a portion of the oligonucleotides bound to the nanoparticles and are bound, as a result of hybridization, to at least a portion of the oligonucleotides bound to the nanoparticles.

A kit for detecting a nucleic acid comprising:

• a substrate having oligonucleotides attached thereto, the oligonucleotides bound to the substate have a sequence that is complementary to a first portion of the nucleic acid;
• a oligonucleotide having an sbp member bound thereto, the oligonucleotide having the bound sbp member having a sequence that is complementary to a second portion of the nucleic acid;
• and
• nanoparticle conjugates comprising (i) nanoparticles having oligonucleotides bound thereto;
• (ii) oligonucleotide having bound thereto a specific binding complement of the sbp member;
• and (iii) a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is bound, as a result of hybridization, to the oligonucleotides bound to the nanoparticle and a second portion of the linker oligonucleotide is bound, as a result of hybridization, to the oligonucleotides having bound thereto a specific binding complement of an analyte.

A kit for detecting an analyte comprising:

• a substrate having oligonucleotides attached thereto;
• an oligonucleotide having a covalently bound thereto a functional group for binding an analyte, the oligonucleotide bound to the functional group having a sequence that is complementary to the oligonucleotides bound to the substrate;
• and
• an aggregate probe comprising:
• (i) at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• and (ii) oligonucleotides having bound thereto a specific binding complement of an analyte, the oligonucleotides having bound thereto a specific binding complement of an analyte are further bound, as a result of hybridization, to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe.

A kit for detecting an analyte comprising:

• a substrate having oligonucleotides attached thereto;
• an oligonucleotide having a covalently bound thereto a functional group for binding an analyte, the oligonucleotide bound to the functional group having a sequence that is complementary to the oligonucleotides bound to the substrate;
• and
• an aggregate probe comprising:
• (i) at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• (ii) oligonucleotides having bound thereto a specific binding complement of an analyte;
• and (iii) a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is bound, as a result of hybridization, to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe;
• and a second portion of the linker oligonucleotide is bound, as a result of hybridization, to the oligonucleotides having bound thereto a specific binding complement of an analyte.

A kit for detecting a nucleic acid comprising:

• a substrate having oligonucleotides attached thereto, the oligonucleotides bound to the substate have a sequence that is complementary to a first portion of the nucleic acid;
• an oligonucleotide having an sbp member bound thereto, the oligonucleotide having a sequence that is complementary to a second portion of the nucleic acid;
• and
• an aggregate probe for detecting an analyte comprising:
• (i) at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• and (ii) oligonucleotides having bound thereto a specific binding complement of the sbp member, the oligonucleotides having bound thereto a specific binding complement are bound, as a result of hybridization, to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe.

A kit for detecting a nucleic acid comprising:

• a substrate having oligonucleotides attached thereto, the oligonucleotides bound to the substate have a sequence that is complementary to a first portion of the nucleic acid;
• a oligonucleotide having an sbp member bound thereto, the oligonucleotide having the bound sbp member having a sequence that is complementary to a second portion of the nucleic acid;
• and
• aggregate probes comprising (i) at least two types of nanoparticles having oligonucleotides bound thereto, the nanoparticles of the aggregate probe are bound to each other as a result of the hybridization of some of the oligonucleotides attached to them;
• (ii) oligonucleotides having bound thereto a specific binding complement of an analyte;
• and (iii) a linker oligonucleotide having at least two portions, a first portion of the linker oligonucleonucleotide is bound, as a result of hybridization, to oligonucleotides of at least one of the types of nanoparticles of the aggregate probe;
• and a second portion of the linker oligonucleotide is bound, as a result of hybridization, to the oligonucleotides having bound thereto a specific binding complement of an sbp member.

A method for nanofabrication comprising:

• providing at least one type of linking oligonucleotide having a selected sequence, the sequence of each type of linking oligonucleotide having at least two portions;
• providing one or more types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on each type of nanoparticles having a sequence complementary to a first portion of the sequence of a linking oligonucleotide;
• providing a complex comprised of strepavidin or avidin bound to two or more biotin molecules, each having a oligonucleotide bound thereto, the oligonucleotides bound to the biotin molecules have a sequence complementary to a second portion of the sequence of the linking oligonucleotide;
• and
• contacting the linking oligonucleotides, complex, and nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles and the first oligonucleotides bound to the biotin to the linking oligonucleotides so that a desired nanomaterials or nanostructure is formed.

A method of nanofabrication comprising:

• providing (i) at least one type of linking oligonucleotide having a selected sequence, the sequence of each type of linking oligonucleotide having at least two portions;
• (ii) at least two types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on the first type of nanoparticles have a sequence complementary to that of the oligonucleotides on the second type of nanoparticles and a sequence that is complementary to the first portion of the sequence of the linking oligonucleotides, the oligonucleotides on the second type of nanoparticles have a sequence complementary to that of the oligonucleotides on the first type of nanoparticle-oligonucleotide conjugates and a sequence that is complementary to the first portion of the sequence of the linking oligonucleotide;
• and (iii) a complex comprised of strepavidin or avidin bound to two or more biotin molecules, each having an oligonucleotide bound thereto, the oligonucleotide bound to the biotin molecule has a sequence that is complementary to the second portion of the linking oligonucleotide;
• and
• contacting the first and second types of nanoparticles, the linking oligonucleotides, and the complex under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles to each other and to the linking oligonucleotide and the hybridization of the oligonucleotides of the complexes to the linking oligonucleotides so that a desired nanomaterials or nanostructure is formed.

A method of nanofabrication comprising:

• providing (a) at least one type of linking oligonucleotide having a selected sequence, the sequence of each type of linking oligonucleotide having at least two portions;
• (b) one or more types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on each type of nanoparticles having a sequence complementary to a first portion of the sequence of a linking oligonucleotide;
• (c) biotin having a oligonucleotide bound thereto, the oligonucleotide bound to the biotin has a sequence complementary to a second portion of the sequence of the linking oligonucleotide;
• and (d) strepavidin or avidin;
• contacting the linking oligonucleotides, biotin having an oligonucleotide bound thereto, and nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles and the oligonucleotides bound to the biotin to the linking oligonucleotides to produce a complex;
• and
• contacting the complex with streptavidin or avidin under conditions effective to allow specific binding interaction between biotin and streptavidin or avidin so that a desired nanomaterials or nanostructure is formed.

A nanomaterial produced by the method comprising:

• providing (i) at least one type of linking oligonucleotide having a selected sequence, the sequence of each type of linking oligonucleotide having at least two portions;
• (ii) at least two types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on the first type of nanoparticles have a sequence complementary to that of the oligonucleotides on the second type of nanoparticles and a sequence that is complementary to the first portion of the sequence of the linking oligonucleotides, the oligonucleotides on the second type of nanoparticles have a sequence complementary to that of the oligonucleotides on the first type of nanoparticle-oligonucleotide conjugates and a sequence that is complementary to the first portion of the sequence of the linking oligonucleotide;
• and (iii) a complex comprised of strepavidin or avidin bound to two or more biotin molecules, each having an oligonucleotide bound thereto, the oligonucleotide bound to the biotin molecule has a sequence that is complementary to the second portion of the linking oligonucleotide;
• and
• contacting the first and second types of nanoparticles, the linking oligonucleotides, and the complex under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles to each other and to the linking oligonucleotide and the hybridization of the oligonucleotides of the complexes to the linking oligonucleotides so that a desired nanomaterials or nanostructure is formed.

A nanomaterial produced by the method comprising:

• providing (a) at least one type of linking oligonucleotide having a selected sequence, the sequence of each type of linking oligonucleotide having at least two portions;
• (b) one or more types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on each type of nanoparticles having a sequence complementary to a first portion of the sequence of a linking oligonucleotide;
• (c) biotin having a oligonucleotide bound thereto, the oligonucleotide bound to the biotin has a sequence complementary to a second portion of the sequence of the linking oligonucleotide;
• and (d) strepavidin or avidin;
• contacting the linking oligonucleotides, biotin having an oligonucleotide bound thereto, and nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles and the oligonucleotides bound to the biotin to the linking oligonucleotides to produce a complex;
• and
• contacting the complex with streptavidin or avidin under conditions effective to allow specific binding interaction between biotin and streptavidin or avidin so that a desired nanomaterials or nanostructure is formed.

A method of separating a selected target nucleic acid having at least two portions from other nucleic acids comprising:

• providing (a) one or more types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on each of the types of nanoparticles having a sequence complementary to the sequence of the first portion of the selected nucleic acid;
• (b) a complex comprised of strepavidin or avidin bound to two or more biotin molecules, each having a first oligonucleotide bound thereto, the first oligonucleotide having a sequence complementary to the sequence of the second portion of the selected nucleic acid;
• contacting the selected nucleic acid and other nucleic acids with the nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles and the first oligonucleotides of the complex with the selected nucleic acid and subsequent formation of an aggregate;
• and
• separating out the aggregate including the selected nucleic acid.

A method of separating a selected nucleic acid having at least two portions from other nucleic acids comprising:

• providing (a) one or more types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on each of the types of nanoparticles having a sequence complementary to the sequence of the first portion of the selected nucleic acid;
• (b) biotin having a oligonucleotide bound thereto, the oligonucleotide having a sequence complementary to the sequence of the second portion of the selected nucleic acid;
• and (c) strepavidin or avidin;
• contacting the selected nucleic acid and other nucleic acids with the nanoparticles and biotin having oligonucleotides bound thereto under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles and the oligonucleotides of the biotin construct with the selected nucleic acid and produce a complex;
• contacting the complex with streptavidin or avidin under conditions effective to allow specific binding interactions between the biotin and streptavidin or avidin and subsequent formation of an aggregate;
• and
• separating out the aggregate including the selected nucleic acid.

A method for accelerating movement of a nanoparticle to an electrode surface comprising the steps of:

• providing at least one type of nanoparticle bound to a charged first member of a specific binding pair and an electrode surface including a second member of a specific binding pair;
• contacting the nanoparticle and the surface under conditions effective to allow binding between the first and the second members of the specific binding pair;
• and
• subjecting the nanoparticle to an electrical field so as to accelerate movement of the nanoparticle to the surface and facilitate binding between the first and second members of the binding pair.

A method of detecting a nucleic acid bound to an electrode surface, the nucleic acid having one or more portions comprising:

• providing one or more types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on each of the types of nanoparticles having a sequence complementary to the sequence of one of the portions of the nucleic acid;
• contacting the nucleic acid and the nanoparticles under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with the nucleic acid;
• subjecting the nanoparticle to an electrical field so as to accelerate movement of the nanoparticle to the surface;
• and
• observing a detectable change.

A method of detecting nucleic acid bound to a surface, the nucleic acid having at one or more portions comprising:

• contacting the nucleic acid with at least two types of nanoparticles having oligonucleotides attached thereto, the oligonucleotides on the first type of nanoparticles having a sequence complementary to a first portion of the sequence of the nucleic acid, the oligonucleotides on the second type of nanoparticles having a sequence complementary to a second portion of the sequence of the nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles with the nucleic acid;
• subjecting the nanoparticle to an electrical field so as to accelerate movement of the nanoparticle to the surface;
• and
• observing a detectable change brought about by hybridization of the oligonucleotides on the nanoparticles with the nucleic acid.

A method of detecting nucleic acid in a sample, the nucleic acid having at least two portions, said method comprising:

• providing a substrate having oligonucleotides attached thereto, the oligonucleotides having a sequence complementary to a first portion of the sequence of a nucleic acid to be detected;
• providing a scattered light detectable nanoparticle probe having oligonucleotides attached thereto, the oligonucleotides bound to the nanoparticle probe having a sequence complementary to a second portion of the sequence of said nucleic acid wherein the oligonucleotides are attached to the nanoparticles in a stepwise ageing process comprising (i) contacting the oligonucleotides with the nanoparticles in a first aqueous solution for a period of time sufficient to allow some of the oligonucleotides to bind to the nanoparticles;
• (ii) adding at least one salt to the aqueous solution to create a second aqueous solution;
• and (iii) contacting the oligonucleotides and nanoparticles in the second aqueous solution for an additional period of time to enable additional oligonucleotides to bind to the nanoparticles;
• contacting said nucleic acid, the substrate and the nanoparticle probe under conditions effective to allow hybridization of said nucleic acid with the oligonucleotides on the nanoparticle probe and with the oligonucleotides on the substrate and form a light scattering complex bound to the substrate;
• illuminating the light scattering complex under conditions effective to produce scattered light from said complex;
• and
• detecting the light scattered by said complex under said conditions as a measure of the presence of the nucleic acid.

A method of detecting two or more nucleic acids in a sample, each nucleic acid having at least two portions, the method comprising:

• providing a substrate having two or more types of oligonucleotides attached thereto, each type of oligonucleotides attached to a different place on the substrate and each type of oligonucleotides having sequences complementary to a first portion of the sequences of one of nucleic acids to be detected;
• providing two or more types of scattered light detectable nanoparticle probes, each type of nanoparticle probes having the oligonucleotides bound thereto, the oligonucleotides bound to each type of probe have a sequence that are complementary to a second portion of the sequence of one of said nucleic acids to be detected, wherein the oligonucleotides are attached to the nanoparticles in a stepwise ageing process comprising (i) contacting the oligonucleotides with the nanoparticles in a first aqueous solution for a period of time sufficient to allow some of the oligonucleotides to bind to the nanoparticles;
• (ii) adding at least one salt to the aqueous solution to create a second aqueous solution;
• and (iii) contacting the oligonucleotides and nanoparticles in the second aqueous solution for an additional period of time to enable additional oligonucleotides to bind to the nanoparticles;
• contacting said nucleic acids, the substrate and the nanoparticle probes under conditions effective to allow hybridization of said nucleic acids with the oligonucleotides on the nanoparticle probes and with the oligonucleotides on the substrate to form a light scattering complex bound to the substrate;
• illuminating the light scattering complex under conditions effective to produce scattered light from said complex;
• and
• detecting the light scattered by said complex under said conditions as a measure of the presence of one or more nucleic acids.

A method for detecting a nucleic acid, the sequence of the nucleic acid having at least two portions, the method comprising:

• providing a substrate having oligonucleotides bound thereto, the oligonucleotides bound to the substrate have a sequence that is complementary to a first portion of a sequence of a nucleic acid;
• providing labels having oligonucleotides bound thereto, at least some of the oligonucleotides having a sequence that is complementary to the sequence of a second portion of the nucleic acid;
• contacting the substrate, nucleic acid, and labels, the contacting taking place under conditions effective to allow hybridization between the oligonucleotides bound to the substrate with the nucleic acids and between the nucleic acid and the oligonucleotide bound to the label so as to form a test substrate having labels complexed thereto;
• contacting the test substrate with an aqueous salt solution having a salt concentration effective to substantially remove non-specifically bound labels;
• and
• observing a detectable change.

Method of detecting a nucleic acid having at least two portions comprising:

• (a) contacting a nucleic acid with a substrate having oligonucleotides attached thereto, the oligonucleotides being located between a pair of electrodes, the oligonucleotides having a sequence complementary to a first portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the substrate with said nucleic acid;
• (b) contacting said nucleic acid bound to the substrate with a first type of labels, the labels being made of a material which can conduct electricity, the labels having one or more types of oligonucleotides attached thereto, at least one of the types of oligonucleotides having a sequence complementary to a second portion of the sequence of said nucleic acid, the contacting taking place under conditions effective to allow hybridization of the oligonucleotides on the labels with said nucleic acid so as to form a test substate having labels complexed thereto;
• (c) contacting the test substrate with an aqueous salt solution having a salt concentration effective to sufficiently remove non-specifically bound labels;
• and
• (d) detecting an observable change.