JP2003507889A - Sensing device using single-electron transistor with chemically gated operation - Google Patents

Abstract

(57) Abstract: A chemically-gated single-electron transistor (60) having predetermined current-voltage characteristics and suitable for use as a chemical or biological sensor operable at room temperature is provided. This single-electron transistor includes a substrate (SuB) formed of a first insulating material, a source electrode (S) and a drain electrode (D) disposed on the substrate, and a source electrode and a drain electrode. Metal nanoparticles (L) having a spatial dimension of a size of about 12 nm or less disposed therebetween. An analyte-specific binding agent is disposed on the surface of the nanoparticle. A binding event that occurs between the target analyte and the binding agent causes a detectable change in current-voltage characteristics.

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to a chemical or biological material.
technology to electronically sense, detect and measure materials, especially molecular receptors
r sensing) and a sensing device that utilizes single-electron transistors as electronic transducers.

BACKGROUND OF THE INVENTION The invention disclosed herein, in a broad sense, demonstrates the advantageous and practical uses of two distinct research fields. The first field is the field effect transistor (FET) in the construction of chemical biological sensing devices.
) And similar electronic logic devices. The second area is the improvement of FET as a digital logic device or its replacement by a single electron transistor (
SET) development is required. Recent developments in their respective fields will now be described in order to give the invention proper legitimacy.

One of the most common types of FETs found in modern digital circuits is the metal-oxide-semiconductor FET, or MOSF.
It is ET. Two general classes of MOSFETs include n-channel enhancement type MOSFETs and n-channel depletion type MOSFETs. The enhancement MOSFET is generally designated by the numeral 10 in FIG. 1A. The highly conductive source region S and drain region D contain n-type silicon (ie, silicon atoms with atomic impurities or “dopants” to add excess free negative charge) and are isolated p-type S.
It is separated by the i-channel 12 and the substrate 14, which contains suitable dopants for adding excess free positive charge. A metal electrode known as the gate G is provided, which is insulated from the substrate 14 by a thin oxide layer 16 (eg SiO ₂ ). When the bias voltage V _gate applied between the gate G and the substrate 14 does not exist, the p-type channel 12 functions as an insulator, so that a current flows between the source region S and the drain region D. It is not possible. In digital electronics this corresponds to the "OFF" state of the device. When a positive potential is applied to the gate G, electrons flow into the channel 12 and basically the source region S and the drain region D
An n-type doped conductive path 18 is created between and. This corresponds to the "on" state.

This behavior of “normally off” type transistors is due to the thin n-type channel 2
2 is inserted below the oxide layer 16 between the source region S and the drain region D.
This can be compared with the behavior of the n-channel depletion type MOSFET indicated by reference numeral 20 in B. In this "normally on" type transistor, a conductive path exists between the source region S and the drain region D in the absence of an applied gate bias. When a negative potential is applied to the gate G, electrons are pushed out of the channel 22. This provides channel 22 with a P-type (insulating) character and eliminates the current path between source region S and drain region D. p-channel MOSFET
Similar devices known as can be constructed by exchanging n-type and p-type materials. In addition, n-channel and p-channel enhancement type MOSFETs are integrated on a single integrated circuit chip to provide complementary MOSFETs.
That is, a CMOS can be formed. Various combinations of CMOS transistors can be used to form the NOT, AND, OR, XOR, and other logic gates that underlie computer operations.

The second important function of MOSFETs is signal amplification. The amplification in the transistor is due to the acceleration of the electrons as they pass through the strong electric field in the channel region. This allows the signal to travel through the computer circuitry without loss of strength.

[0006] The important advantages and capabilities afforded by FET technology are:
It has led to improvements in the field of ical and biological sensors or “biosensors”. These developments are partly based on the recognition that conventional chemical or biological labeling methods such as isotope labels, fluorescent labels, bioluminescent labels and enzyme labels, as well as spin labels, have certain disadvantages. Generally, labeling technology does not have high sensitivity and specificity (or selectivity), and is not suitable for miniaturization.

Therefore, many types of biosensors have been developed that can be assembled from conventional FET type devices. US Pat. No. 4,777,019 to Dandekar is an example of a device that converts a biological chemical signal into an electronic signal for detecting or measuring a biological material. . In Dandekar's device, a biological layer made of a mass of semiconductor material (such as silicon nitride or silicon oxide) doped with adenine was provided on top of the insulated gate layer of the FET. The two hydrogen-bonding bridges associated with each adenine molecule are thymine (
thymine) molecule, so the device may be placed in a solvent to detect the presence and concentration of thymine. The electrostatic field of adenine paired with thymine is different from that of unpaired adenine, and the difference in electrostatic field is F
The conductivity of ET is changed to change the source / drain current flowing through the FET. In addition, macromolecules such as poly-Uracil-mRNA bind to adenine sites, allowing the device to detect DNA species in solvent.

A FET-based biosensor for analyzing biologically active substances is Forres
It is also provided in US Pat. No. 4,778,769 issued to Mr. T. et al. A gate insulator formed of a layer of insulating material is disposed on the p-type silicon substrate.
The p-type substrate includes two diffusion regions of n-type silicon to be a source region and a drain region. The gate electrode is disposed on the gate insulator. Specific binding partner for the ligand sought by analysis
An amount of agent, known as, is immobilized on the gate electrode. When the gate electrode is below the threshold potential (V _T ) of the device, no electrons can pass from the n-type source region to the p-type substrate, so almost no current can flow between the source and drain regions. Can not. When the gate electrode potential (V _g ) is higher than V _T , an electric field is generated through the gate insulator, causing repulsion of majority p-type carriers from the insulator / substrate boundary, and between the source region and the drain region. A depletion region in which negative carriers dominate is formed in the. When a voltage potential is applied between the source region and the drain region, the drain current will flow.

Another biosensor utilizing a FET as an electronic converter is disclosed in US Pat. No. 4,877,582 to Oda et al. A chemical or biochemical receptor is placed on top of the gate of the FET. Receptors include membranes, antibodies or immobilized enzymes on microorganisms. In one embodiment, urease immobilized at the gate with albumin and glutaraldehyde is used to detect the presence of urea.

US Pat. No. 4,894,339 to Hanazato et al. Also discloses the use of an immobilized enzyme membrane in association with a semiconductor sensor. The enzyme membrane consists of an aqueous solution containing glucose oxidase as an enzyme, polyvinyl pyrrolidone and 2,5 bis (4'-a).
zide-2'-sulfobenzal) cyclopentanone sodium salt (2,5-bis (4'-azide-2'-s
It is produced by coating the base with a water-soluble photosensitive resin containing ulfobenzal) cyclopentanone sodium salt) and bovine serum albumin. A portion of the dried coating is then irradiated with UV light to introduce photocrosslinking and treated with glutaraldehyde to introduce chemical crosslinking for enhanced mechanical strength. The sensor is a hydrogen ion sensitive insulated gate FET, that is, a pH-ISFET chip with two pH-IS, on an epoxy resin board.
It is configured by attaching a device including a FET. This enzyme membrane has a pH-
Located on either of the ISFETs, a reference electrode is provided. Communication with the measuring circuit is realized by means of the wires.

US Pat. No. 5,039,390 to Hampp et al. Is another example of a chemical sensor that includes a chemically sensitive film bonded to the gate of a FET. Depending on the membrane chosen, the device can be an ion, gas, enzyme, antibody or well, or hydride-forming DNA.
/ Sensitive to hydride-forming DNA / RNA groups.

A sensor system capable of simultaneously detecting a wide variety of chemical substances and biological substances is disclosed in International Publication No. WO93 / 08464 (International Application No. PCT / US92 / 0).
8940). An array of FET-based devices is mounted on a single substrate with calibration and associated circuitry. Each device is provided with a separate and specific receptor configured to measure different types of substances.

US Pat. No. 5,653,939 issued to Hollis et al. Also includes FETs each including a particular probe or receptor configured to detect a particular target molecule.
Disclosed is a system that includes an array of base devices.

A FET-based chemical and biological sensor as described above.
sensors) have proven useful in a wide variety of applications. Unfortunately, further improvement of its utility as a device for chemical-biological transformations is based on the F
Limited to the same extent as ET technology. MOSFET devices have dominated computer technology for several reasons including low operating voltage (eg 0.1V), low power consumption, high speed, and ease of miniaturization. In the past, MOSFETs have been able to be miniaturized by reducing each component (that is, channel, source, drain, conducting wire, etc.) at a fixed ratio and operating as before. As the limits of photolithography rapidly approach, it is becoming apparent that continued increases in circuit density require fairly dramatic changes in the design, manufacture, and operation of transistors. It is not entirely clear whether the operating principle of such a MOSFET can be scaled as it is when the size is reduced to 100 nm or less. As the npn region of a transistor shrinks, the ability to control the flow of electrons is dominated by the quantum mechanical probability that the electrons will only tunnel through the npn boundaries. Moreover, as the transistor density increases, the probability that one electron will tunnel through an adjacent transistor increases. These tunneling processes cause errors in data processing and storage. As the size of a MOSFET decreases, the ability to fabricate any two transistors to have the same electrical characteristics is compromised (ie, it becomes difficult to achieve a particular dopant concentration in any two transistors). It is of interest. Currently, a better approach for many applications is to avoid rather than try to exploit the effects of quantum physics.

One such approach has been to develop devices based on single electron nanoelectronics as an alternative to bulk current devices for transmitting digital information. Heretofore, this approach has been pursued solely for the purpose of improving methods for processing digital information rather than chemical transformations. I am interested in nanometer-sized metal particles or semiconductor particles (nanocluster (nanocl
usters), metal islands, metal dots, or quantum dots) that operate on the basis of a single electron flow, ie, single-electron tunneling theory. Single electron transistors (“SET (single electron transistors)”
)). SET is in principle similar to conventional FETs.
However, in SET, the electrons in the metal island are transferred one by one (co
Rrelated transfer means that the energy required to charge the island by a single electron (e ² / C _T , where “e” is the electric charge of the electron and C _T is the capacity of the entire island) is thermal energy (kT). ) Occurs when it is relatively large compared to the energy supplied by. Thus, the logical operation in SET is based on single-electron tunneling using nanometer-sized dots.

For conventional electronic devices, the discrete nature of the single electron charge is not important at the macroscopic level. For example, a macroscopic capacitor coupled to a battery is charged by displacing electrons from fixed positively charged ions on one plate and transmitting them through a dielectric material to a second plate. This work required for the battery to perform this work is given by equation (1) below. W = q ² / 2C where q = ne is the total charge stored, “e” is the charge of a single electron, and C is the (electrostatic) capacitance. In a typical computer capacitor with a picofarad (pF) capacitance and an applied voltage potential of, for example, 100 mV, the total charge would be millions of electrons. Importantly, if the capacitor junction were thin enough that a single electron could tunnel from one plate to another, there would be no observable effect on the charge potential. Thus, when the capacitor is charged, the electrons are constrained to an integer value, but in macroscopic devices the "particle nature" of the electrons is not apparent.

On the other hand, if the junction capacitance is small (<−10 ⁻¹⁸ F) and the resistance is high, the charging energy and tunneling of a single electron in the circuit will affect the current-voltage (IV) characteristics of the capacitor. Can be given. For example, FIG. 2 illustrates bulk metal-insulator-nanocluster-insulator-bulk metal-insulator-nanocluster-insulator-bulk, generally indicated by the numeral 30.
k metal double-tunnel junction), or "MINIM" or "MID"
2 shows a device that includes an "IM". (In this disclosure, the terms “cluster” and “
"Particle" is used interchangeably to describe both semiconductor particles and metal particles less than about 50 nm in diameter. ) Generally, a layer 32 of insulating material (which may be a semiconductor) is disposed between two metal regions or electrodes 34,36. The metal nanoparticles or nanoclusters QDs are arranged in the insulating layer 32. The first and second insulating junctions J ₁ and J ₂ are effectively defined on either side of the nanocluster QD. When the MINIM 30 is biased by an external voltage source V _ext , a significantly different current response is observed as the MINIM 30 or nanocluster capacitors are charged. As shown in FIG. 4, current steps are observed and the steps are separated by a voltage plateau that can span hundreds of millivolts. This response is known as the Coulomb stairs. Each current step corresponds to the addition of a single electron to the nanocluster QD.

[0018]   In the semi-classical approach, as shown in Figure 3A, MINIM30
Are arranged in series and ideal voltage source V_extCapacitance and resistance C driven by₁, R ₁ , And C₂, R₂Are treated as two capacitors with. (The term "ideal" is
Here we describe a battery with zero internal resistance that can deliver charge instantaneously.
Used for. ) The state of this system is for each joint J₁, J₂Electric power
Pressure drop (V₁, V₂) And the number of electrons Q on the nanocluster QD₀It is described by.
Then the dynamics of this system is that one electron is the first junction J₁and/
Or the second joint J₂Tunnel through Q₀Is described by the probability of changing (
That is, the probability approach). These tunnel events occur when electrons are bulk metals or
From pole 34 to first junction J₁When tunneling to the nanocluster QD via
It depends on the change in energy of each electron.

For those skilled in the art to understand better, this dependency is discussed by discussing that this occurs when MINIM 30 is placed in contact with electrodes 34, 36 before an external bias is applied. It can be quantified theoretically. Electrode 34 and electrode 36
And the Fermi level of the nanocluster QD try to be aligned by the electrons tunneling from the electrodes 34 and 36 to the nanocluster QD. In general, the Fermi levels cannot be aligned exactly, but the energy will be offset by one or more electrons. This is due to the discrete nature of the charges and the impurities present in the junction region.
However, for the purpose of achieving a simplified quantification, it can be assumed that this alignment is perfect and that the quantum mechanical energy levels are energetically closer than the electrostatic energies. The deviation of the Fermi level alignment can be explained by adding a voltage offset term to the equation (8) described below. Similarly, this quantum mechanical energy level assumption is valid for metal particles larger than about 5 nm in diameter. However, semiconductor particles exhibit quantum effects at much larger sizes. Finally, it is assumed that the resistance of the junctions J ₁ , J ₂ (R> h / e ² ) is so great that electrons are localized at one or the other end of the junction.

When the system is electrostatically in equilibrium, a potential is applied by the voltage source V _ext and n electrons tunnel into the nanocluster QD via the thin insulating barrier at the junction J ₁ . It can be found that the value n is a function of the applied potential (or applied energy). Since this process is described by energy, the quantity Δ
A localized approach is taken to obtain E ₁ = E _f −E _j . ΔE ₁ is the energy difference between the junction J ₁ before (E _j ) and after (E _f ) tunneling of electrons. This quantity represents the energy that must be supplied by the external voltage source V _ext to place an electron on the nanocluster QD. Explaining with reference to FIG. 3B, the initial state is the energy of the junction J ₁ charged with n electrons. This energy is given by equation (2). E _j = (ne) ² / 2C _T where “e” is the charge of a single electron, C _T = C ₁ + C ₂ is the total cluster capacity, ie one electron when tunneling through the first junction J _1. Is the capacity to "see". The final energy state E _f is the energy of the system in which one electron exists on the nanocluster QD. By placing an electron on the nanocluster QD, the potential drops by V ₁ and the polarization charge flows through the circuit. As a result, the battery V _ext does the work of eV ₁ and brings one electron from the second electrode 36 to the first electrode 34. The energy associated with charging the cluster charge with only one electron is given by equation (3) below. E _f = eV ₁ + [(Q ₀ −e) ² / 2C _T ]

By expanding the second term of Expression (3) and subtracting Expression (2), the following Expression (4) is obtained. _{E f -E i = eV 1 -} (Q 0 e / C T) + (e 2 / 2C T)

The energy of the system is completely described by the change in cluster charge and the work done by the voltage source V _ext . The relationship between V ₁ and V _ext is needed to calculate the external voltage that must be applied by the battery or potentiostat. First, the law of conservation of charge gives equation (5). C ₁ V ₁ = C ₂ V ₂

Next, Kirchhoff's loop law gives equation (6). V _ext = V ₁ + V ₂

By combining the equations (5) and (6), the equation (7) is obtained. V ₁ = C ₂ V _ext / C _T

Finally, Equation (8) is obtained. ΔE1 = (eC ₂ V _ext / C _T ) − (eQ ₀ / C _T ) + (e ² / 2C _T )

The first term in equation (8) is the work done by the voltage source V _ext to maintain V 1 after one electron has tunneled through the nanocluster QD. The second and third terms represent the charging effect of a single electron. The second term is the additional work required to tunnel a single electron when it already exists on the nanocluster QD. This term provides the voltage feedback necessary to prevent more than n electrons from tunneling into the cluster as the voltage increases. Here, n is the number of steps (for example, 1e ⁻ , 2e ⁻ , ... In FIG. 4). In contrast to the macroscopic scale, which we haven't noticed a single electron before,
The movement of a single electron through a nanoscale capacitor, such as device 30, causes a substantial energy change in the circuit. This prevents more than the allowed number (n) of electrons from being on the nanocluster QD at the same time.

The current staircase phenomenon shown in FIG. 4 can be explained by considering the allowed voltage change ΔV> 0 at the junction J ₁ . If this is not the case, the electron will soon tunnel back to where it came. Therefore, the formula (9) is established. V _ext > Q ₀ / C ₂ -e / 2C ₂

In the case of nanoparticles that are initially neutral (Q ₀ = 0), an external voltage e / 2C ₂ is required before current can flow through the circuit. This phenomenon is called Coulomb gap
) Or Coulomb blockade (Coulomb blockade) is called. When this voltage is reached, a single electron tunnels to the nanocluster QD. The electrons do not remain on the nanocluster QD indefinitely, but quickly tunnel off via the next junction J ₂ (at about 100 ps depending on the ratio R ₂ C ₂ / R ₁ C ₁ ). However, it remains long enough to provide the voltage feedback needed to prevent additional electrons from tunneling to the nanocluster QD simultaneously. Thus, a continuous current l = e / 2R ₂ C _T single electrons flowing through the circuit (factor e / RC comprises units of charge / hour). Each additional electron placed on the nanocluster QD has a voltage e / C ₂
Need as is. This leads to an overall voltage increment of 1/2, 3/2, 5/2, etc. in the current step phenomenon shown in FIG. 4 (the magnitude of the current step after the previous step is e / R ₂ C ₂ ).

With respect to the design of MINIM 30, the junction capacitance and resistance must be optimized. In the MINIM IV curve by simulation, the sharpest step is
C ₂ and R ₂ >> are shown to be observed for C ₁ and R ₁ . As C ₂ / C ₁ and R ₂ / R ₁ approach 1, the zero current plateau remains at 0 V, but the current step disappears. If R and C for junctions J ₁ and J ₂ are equal, the electrons will tunnel junctions J ₁ and J ₂ at the same rate. Thus the voltage feedback required to see the current step is compromised. Unfortunately, as the bond thickness increases, C decreases but R increases, so these ratios can only be optimized by constructing the bond from materials with different dielectric properties.

Thermal effects are another significant design consideration. SETs have been constructed using polycrystalline silicon or polyacetylene as quantum dots. Since these devices must be cooled to 4K to create the SET phenomenon,
Not practical. To avoid the heat activated tunneling process, e /
2C ₂ >> kT must be satisfied. As T increases, the single-electron current step is gradually extinguished and an ohmic response (ie, a linear IV curve) is observed. Generally, room temperature operation of the SET is less than about 12 nm in diameter, preferably 10 n.
Transistor miniaturization down to the molecular level is required using nanoparticles of less than m. Such devices are better built using self-assembly methods, that is, assembly by chemical interaction from a liquid layer opposite the lithographic system. US Pat. No. 5,4 granted to Smith
No. 20,746 discloses a SET device capable of operating at room temperature provided with a cluster of pure carbon atoms, fullerene (C ₆₀ ), as quantum dots. The device consists of a layer of insulating material (such as silicon dioxide) located between two conductive layers. One or more fullerenes are disposed in the insulating layer. The device is then biased by the battery by connecting the conductor to a conductive layer. The device acts as a sufficiently small double barrier tunnel structure so that each fullerene experiences the Coulomb Brocade effect at any tunnel current.
Under low bias (below a certain critical threshold voltage), the fullerene charging voltage will be greater than its applied bias, and no current will flow. That is, the Coulomb blockade effect blocks electrons from tunneling through the insulation towards the fullerene. When the critical voltage is reached, an electron leaves the first conductive layer and tunnels through the insulating material to the fullerene. The electron then exits the fullerene and continues to tunnel through the insulating material to the second conductive layer. The charging voltage that charges two electrons onto the fullerene is greater than the charging voltage of a single electron. Thus, if the voltage applied to the device is maintained above the charging voltage of a single electron and below the charging voltage of two electrons, then only one electron will be present on the fullerene at a time. As a result of this behavior, the device should have a substantially stepped current-voltage curve (IV characteristic).

To emulate the functionality of a MOSFET, a three-terminal SET device with a spatially well-defined MINIM double tunnel junction can be provided with a gate electrode located near the nanoparticles. . The flow flow of single electrons from the source to the drain can be controlled by injecting (or removing) single electrons from the nanoparticles through the gate electrode.

Unfortunately, photolithography techniques for producing complex SET structures are around 100n
Limited to minimum size features. Similarly,
E-beam lithography can create features on the order of 5 nm,
Expensive, slow, and not yet readily available. Further, the relatively simple metal evaporation method can realize the feature of down to 10 nm in the metal island, but it is difficult to control the exact arrangement and dispersity of the metal island. In contrast to lithography and metal evaporation, liquid-phase chemical synthesis can achieve clusters of almost arbitrary size.

Therefore, the best approach to date for manufacturing SET devices has been to organize the material into a pre-designed composite structure in the liquid phase by chemical directivity. It is self-assembly defined. Chemically synthesized nanoparticles offer several advantages as SET components. The most important one is the small size. Metal and semiconductor nanoparticles can be prepared in solution with an average diameter of tens of angstroms or more. Adsorbed or covalently attached ligands can serve as stabilizers for aggregates and can be used to incorporate chemical functionality into the nanoparticles. Importantly, nanoparticles can be immobilized between multiple insulating films by electrostatic or covalent chemistry.

[0034]   An example of a self-assembled SET that can operate at room temperature was given to Mr. Yamashita
U.S. Pat. No. 5,646,420. Lipid bilayer on carbon substrate
Thus it is supported on one outside and supported by the conductive layer on the other outside.
Be held. Each of the lipid bilayers has a hydrophobic group facing inward and a hydrophilic group facing outward.
Contains groups symmetrically. Α-helical conformation of bacteriorhodopsin and four GCs
A protein material with CC segments is placed between each layer of the lipid bilayer
To be done. The protein material functions as an insulating material. Quantum dots are the protein
Supported by the material. It is flavin or 7-acetyl-10-medium
Conductivity such as chill isoalloxazine (7-acetyl-10-methyl-isoalloxazine)
Made from organic compounds, where the acetyl group is the G of the protein material sequence
It binds to the sulfur atom of partial cysteine. A pair of electrodes function as source and drain
And each ortho position of the four phenyl groups corresponds to each part
Mn bound to an alanine amino group (ie end amino acid) ³ + terrakis-tetraphenyl-porphyrin inner complex salt
Made of Electrodes are attached to the upper and lower ends of the protein material, respectively.
The polyacetylene control gate (or other organic polymer with π electrons) is
Is placed between the hydrophobic groups and binds to the quantum dots. Finally, the outer terminals
It is inserted into the carbon substrate through the hole.

Single electron transfer occurs via a single flavin molecule by the tunnel effect.
The transition level closest to the Fermi level is the thermally excited level (25 mV) of the electron at room temperature.
Higher than room temperature, the SET phenomenon at room temperature is possible. The outer terminal connects to the control gate,
Application of a voltage to the control gate causes a change in the potential energy of the flavin molecule. Increasing the voltage creates an additional transition level of electrical conduction, resulting in a stepped IV characteristic. The present disclosure shows that this device may be useful as a highly miniaturized electronic switch.

The inventor believes that the benefits provided by the devices exhibiting the SET phenomenon described above have not previously been applied in the field of chemical and biological transformations. Therefore, there has been a long felt need for SET-based chemobiosensors that take advantage of increased sensitivity, selectivity, and miniaturization. The inventor has discovered such a device. The details will be described below.

DISCLOSURE OF THE INVENTION The present invention combines one or more chemical and / or biological sensing elements with a SET-based transducer to suit a wide variety of portable, small scale sensory systems and applications. can do. From the present disclosure, (i) a single molecule,
Ability to detect single molecule binding events, and single molecule redox reactions, (ii) small dimensions capable of integrating thousands to millions of sensors on a single chip or substrate, (iii) fast response time. , (Iv) selectivity, (v) low cost, and (vi
Many advantages are immediately apparent, such as low power consumption.

From the above, the chemically gated single-electron transistor provided by the present invention has a predetermined current-voltage characteristic, is configured to be used as a chemical or biological sensor, and is operable at room temperature. Is. This single-electron transistor has a substrate formed of a first insulating material, a source electrode and a drain electrode disposed on the substrate, and a substrate having a thickness of about 12 nmn or less disposed between the source electrode and the drain electrode. Metal nanoparticles having a spatial dimension of a size. Detectable substance-specific binding agent (analyte-spec
ific binding agent) is placed on the surface of the nanoparticles. The binding event that occurs between the target analyte and its binder causes a detectable change in the current-voltage characteristics.

The present invention also provides devices for sensing chemical or biological substances.
This device has a predetermined current-voltage characteristic, and has a substrate to be insulated, a source electrode arranged on the substrate, a drain electrode arranged on the substrate, and a source electrode and a drain electrode. And an array of metal nanoparticles each having a spatial dimension of about 12 nm or less, and a single electron transistor. An analyte-specific binding agent is placed on the surface of each nanoparticle, where a binding event between the target analyte and one or more nanoparticles causes a detectable change in current-voltage characteristics. .

The present invention also provides another device for sensing chemical or biological substances. This device comprises a plurality of single-electron transistors having predetermined current-voltage characteristics. Each single-electron transistor includes an insulated substrate, a source electrode and a drain electrode disposed on the substrate, and metal nanoparticles disposed between the source electrode and the drain electrode. Each nanoparticle has a spatial dimension of about 12 nm or less. A detectant-specific binding agent is placed on the surface of each nanoparticle, where the binding event between the target detective agent and the binding agent causes a detectable change in the current-voltage characteristics. The voltage source communicates with the single electron transistor, and the integrated circuit communicates with the single electron transistor. The integrated circuit is configured to interpret changes in the current-voltage characteristics of a single transistor caused by the occurrence of a coupling event.

The present invention also provides yet another device for sensing chemical or biological substances. The device comprises an insulated substrate, a plurality of elongated lower electrodes spaced apart from each other on the substrate, and a plurality of spaced lower electrodes spaced from one another across the lower electrodes. A plurality of elongated elongated upper electrodes.
The upper electrode and the lower electrode cooperate to form a lattice pattern including a plurality of intersecting regions formed by intersecting the upper electrode and the lower electrode. Each intersection area defines a test site. Single electron transistors are built at each test site. Each single-electron transistor has a predetermined reference current-voltage characteristic and includes metal nanoparticles disposed between an upper electrode and a lower electrode at each test site. Each nanoparticle has a spatial dimension of about 12 nm or less and is stabilized by an insulating medium. Each nanoparticle has an analyte-specific binding agent located on the surface of each nanoparticle, and the binding event that occurs between the target analyte and the nanoparticle causes the nanoparticle's current-voltage characteristics to change. A detectable change is triggered. The voltage source communicates with the upper and lower electrodes. The integrated circuit is configured to interact with the test site and interpret changes in the current-voltage characteristics of a single transistor caused by the occurrence of a coupling event.

Another chemically gated single-electron transistor provided by the present invention has predetermined current-voltage characteristics, is configured for use as a chemical or biological sensor, and is operable at room temperature. is there. This single-electron transistor comprises a lower insulating substrate, an intermediate metal layer disposed on the lower insulating substrate, and an upper insulating substrate. A well is formed in the upper insulating layer and the intermediate metal layer, defining a source electrode on the first portion of the intermediate metal layer and a drain electrode on the second portion of the intermediate metal layer. An upper metal layer is disposed on the well and on the upper insulating substrate. Metal nanoparticles are disposed within the well, have spatial dimensions no greater than about 12 nm, and are stabilized within the insulating medium. A molecular receptor attaches to the surface of the upper metal layer, where a binding event between the target analyte and its molecular receptor causes a detectable change in the current-voltage characteristics.

The present invention also provides a single electron transistor probe. The probe is configured to scan the surface for the presence of chemicals or biologicals, and it has a conductive probe tip and a spatial dimension of 12 nm or less and a metal attached to the probe via an insulating medium. The nanoparticle and the analyte-specific binding agent attached to the nanoparticle are provided. The binding event that occurs between the target analyte and the analyte-specific binding agent causes a detectable change in the current-voltage characteristics.

The present invention further provides a single electron transistor device having predetermined current-voltage characteristics that is operable at room temperature and useful for sensing chemicals.
The single electron transistor comprises a substrate formed of a first insulating material, a metal layer disposed on the substrate, and an insulator defining a double tunnel junction. The insulator is formed in a region of the metal layer and includes an oxide of the metal layer. Further, at this time, the insulator divides the metal layer into a first region, a second region, and a third region. The first region defines a source electrode, the second region defines a drain electrode, and the third region defines metal nanoparticles having spatial dimensions of about 12 nm or less. Binding of the target molecule to the nanoparticles results in a detectable change in current-voltage characteristics.

From the above description, it is an object of the present invention to provide a chemical or biological sensor that operates under the single electron transfer principle.

Another object of the present invention is the use of molecular receptors or detector specific binders found in field effect transistor based devices in a practical and operable single electron transistor based device. It is to integrate the advantages obtained by.

A further object of the invention is to provide a gate for a transistor constructed from metal nanoparticles and modified by a chemical or biological binder.

Some and other objects of the invention that have been described above will become apparent as the description proceeds with reference to the accompanying drawings, which are best described below.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. The inventor notes that when a gate electrode is attached to a SET device, injecting (removing) a single electron into the nanoparticle can dramatically change the current behavior of the device. In other words, the IV curve of the SET device is very sensitive to the charge placed on the nanoparticles by the outer source. If a single electron is injected into the nanoparticle from the gate electrode, the current through the SET device can change by hundreds of picoampere (pA).

DETAILED DESCRIPTION OF THE INVENTION The present inventor has found that the same current sensitivity of the SET device is similar to the chemical SET device.
al gating device (chemical gating)
mechanism)). Embodiments of chemical SET devices, examples of which are described below, are sensitive to the presence of a single detector molecule bound to the surface of an insulator or nanoparticle. Chemical SET devices include self-assembled monolayers, proteins, DNA, minerals,
It can be made more selective by introducing various analyte-specific binding agents on the surface or the surface capped with the ligand.

The great challenge in incorporating single-electron devices into nanoscale electrical circuits is the SET for impurities that may remain on or near the nanoparticles.
It is the sensitivity of the electric current. Impurities shift the SET current-voltage curve, making it difficult for any two SET devices to be electronically equivalent. It has been found that particle-capping ligands can be used as "chemical gates" to manipulate the SET current. However, if it is determined that the nanoparticles selected for use in SET-based sensors need to be stabilized by ligand capping, the resulting capped nanoparticles can be used in chemical sensor applications. It must be further determined whether it is sensitive to the physical changes sought after, or whether binding agents or molecular receptors with specificity for the analyte can be attached to the capping material.

Exemplary analytical results of the present invention are illustrated in FIGS. 5-9. Ligand-stabilized gold (Au) nanoclusters were observed in aqueous solution. Two different ligands, i.e. octanethiol (octanethiol) (C ₈ -Au, diameter 5 nm)
When, the pK _a to 12 when bound to the Au nanoclusters Garubinoru (Galvi
nol) (Gal-Au, diameter 3 nm) was discussed. In FIG. 5, gold nanoclusters 42 are capped with octanethiol ligands 44 and are placed above a flat Au substrate 46 insulated with an octanethiol coating 48. In FIG. 7, the gold nanocluster 42 is capped with a galbinol ligand 52 (GAL). The individual nano-cluster 42 is a scanning tunneling microscope (“STM (scanning tunneling micro
scope) ") 54. As shown in FIGS. 6A and 6B and FIGS. 9A, 9B, 9C, and 9D, respectively, C ₈ -Au (pH
5 and 12) and Gal-Au in water (pH is 5, 8, 10 and 12), a clear IV step (Coulomb step curve) was observed. These current step and voltage plateau represent the function of SET.

Since there is no chemical difference in C ₈ -Au between the two pH values tested, p
Little change in the IV behavior as a function of H resulted. The voltage plateau width (ΔV) is 59 ± 7.8 mV at pHs 5 and 12, respectively.
And 63 ± 4.6 mV. The ΔV value can be used to evaluate cluster capacity using ΔV = e / C, which is approximately 2.7 ± 0.30 aF / cluster and 2
． 5 ± 0.10 aF / cluster (0.05 aF / nm ² ) is given. However, as the pH increased as shown in Figure 8, galvinol (galvinol)
) Is converted to galvinoxide anion (galvinoxide anion). As a result, the change in the behavior of IV with respect to Gal-Au was deprotonated (deprotonatio).
It occurs according to n). All steps (I-V) to positive bias potential from pH 5 to pH 8
The subtle shift of the curve) (about 30 mV) is noteworthy. This shift is even stronger in the IV curves obtained at pH 10 and 12 (from about 60 mV to 120 mV). In addition, ΔV is p ± 74 ± 7.8 mV at pH 5
It decreases to 64 ± 4.0 mV at H8 and 48 ± 5.6 at pH12.

The chemically induced changes in the SET step described above are explained by discussing the changes and structural changes that occur in the galvinol monolayer upon deprotonation. At pH 5, galbinol is in its protonated, neutral form. Therefore, the Gal-Au Coulomb staircase at pH 5 is generally symmetrical with the first step centered at 0V. Galbinol is converted to the galbinoxide anion as the pH increases. The increased negative charge on the nanoclusters has two consequences. First, the total capacity of the cluster is increased. Based on ΔV, the amount of increase in nanocluster capacity was 2.2 ± 0.24aF / cluster (0.06a) at pH 5.
F / nm ² ) to 2.5 ± 0.14a F / cluster (0.09a) at pH 8
F / nm ² ), 3.3 ± 0.31 aF / cluster (0.12 aF) at pH 12
/ Nm ² ) and so on. The second result is an increase in the negative charge on the nanocluster surface. In solid state SET devices, negative charges from either impurities or the application of gate electrode bias located near the metal islands shift the Coulomb stairs to a positive bias potential. Its shift to a positive bias potential in the Gal-Au system is qualitatively consistent with the solid state measurements. Potential shift and capacitance variation, only the C ₈ In -Au without Gal-Au, and Gal-
The fact that it was observed at three different pH's of the same ionic strength for Au proved the feasibility of a pH-gated ET device.

Accordingly, a SET device for directly measuring the pH value of a solution to detect redox events or analyte binding events known to occur as a result of changes in pH value is shown in FIG. Was constructed by the inventor as follows. The source electrode S and the drain electrode D are arranged on the surface of the support substrate SUB in a positional relationship with a gap. The support substrate SUB is formed of a usual insulating material such as silicon, silicon dioxide or polymer. Instead, the substrate SUB is made of a conductive material,
It may be insulated by an insulating material such as a thiol layer. A nanoscopic amount of a metal such as silver gold or platinum is disposed between the source electrode S and the drain electrode D and functions as a metal island or a nanoparticle QD. Nanoparticle QD
Thiol, preferably galvinol, which reacts rapidly to changes in pH
capped with a ligand substance L such as nol). Next, a suitable lead wire LW or the same kind is connected to the source electrode and the drain electrode. Changes in the pH value of the solution in contact with the device will cause a shift in the step IV curve as already explained. This change is accurately measured and can be interpreted with the help of electrical circuits or other well known means.

A SET-based chemically gated sensor device, indicated generally by the numeral 70, has a basic structure similar to the pH-dependent SET device 60 and allows the detection of a particular analyte, the target molecule, It may be used as a transduction element in a wide variety of sensors or test sites designed with different types of chemical gates for the selective detection of compounds or biological substances. The inventors have done this either by directly attaching the detector specific binding agent or molecular receptor A to the nanoparticle QD, or by capping the ligand, I (which acts as a double tunnel junction). It was realized by Depending on the particular binder selected, there will be an observable change in the IV characteristics of SET device 70 when Detectant B binds to Binder A. In such a configuration, the capping ligand or insulator I acts as a double tunnel junction and the binder A acts as the chemically operating gate electrode of the SET device. A wide variety of binders A may be selected, including self-assembled monolayers, proteins, antibodies or antigens, DNA and minerals. As a result, a wide variety of detected substances B can be detected by well-known binding relationships and chemical properties.

Current detection method (amperometric mode) or potential difference detection method (potentiometric mode)
) Are both possible in the sensor device 70 as shown in FIGS. 12A and 12B. The solid line represents the IV curve of the sensor device 70 when the detected object B is absent, and the dotted line represents the curve when the detected object B is present.

In current sensing, the source-drain potential is biased at some point on the IV curve at some voltage plateau, such as by using a battery or potentiostat. When the analyte B binds to the nanocluster QD, the charge on the nanocluster QD changes, resulting in a change in the IV characteristics of the sensor device 70, effectively as shown in FIG. 12A. The entire IV curve shifts the current up or down by one electron. Since the bias voltage is fixed by the potentiostat (V _hold ), the current flowing through the circuit is ± ne, where n is the number of charges injected (+ e) into or removed (−e) from the nanocluster QD. Just have to change. In other words, the sensor device 70 must stay on the same current step after charge injection (or removal). The only parameter that is allowed to change is the current. Therefore, a current flows (or stops depending on the configuration or bias of the sensor device 70) due to the change in the nanocluster charge.
The sensor device 70 implements a "chemical" gate.

In the potential difference detection method, as shown in FIG. 12B, a fixed current is applied to the source electrode S.
Is forced to flow between the drain and the drain electrode D, and the potential across the junction is monitored. In this case, the current is fixed (I _hold ), so the potential must change to maintain the fixed position of the current step. In fact, a large change in the potential (about 200 mV for a nanocluster with a diameter of 10 nm)
Expected in response to the addition of a single charge to D.

In either case, the IV curve of the sensor device 70 is sensitive to the mere change 1e ^{− of} charge injected into the nanoclusters QD, so that a single electron detector can be detected. Moreover, since the signal conversion is based on the movement of a single electron, response times on the order of 10 ⁻¹² are possible.

FIG. 13 is a diagrammatic representation of our sensor device, in the absence of a molecular binding event, a single electron flow between metal leads occurs across a nanocluster QD. When the target object B is bound to the molecular recognition element A, the “gate” is closed and the IV
Curve shifts may be detected. FIG. 14B is a corresponding plot of current as a function of time, showing that the operation of sensor device 70 can be beneficially utilized as digital information.

Many embodiments are constructed from the novel devices described above. For example, in FIG. 15, to increase the area of the test site and improve the chances of detecting the desired detection,
Alternatively, an array 80 of nanoparticles or nanoclusters is provided between the source electrode S and the drain electrode D to measure the concentration of the analyte in solution. The cluster array 80 includes an external voltage source V and an integrated analysis circuit I for interpreting changes in IV characteristics.
It is electrically connected to C.

In addition, a test card or wearable badge may be provided, generally indicated at 90 in FIG. The wearable badge 90 comprises an integrated circuit IC, a source potential such as a watch battery WB, and a plurality of sensing cluster arrays 80. The individual sensing arrays 80 or groups thereof may include different binding agents attached to their respective nanoparticles or capping ligands, so that the wearable badge 90 is capable of detecting a variety of different analytes. . A well-known method is a sensing array 8 having a different integrated analysis circuit IC.
It may be used to be able to distinguish between the various signals received from zero. For example, the location of each individual sensing array 80 and the identification of the binding agent or the corresponding analyte detected by that particular sensing array 80 may be digitized. Thus, a change in the IV characteristics of a particular sensing array 80 may be used as a positive test for the presence of a detective known to bind to the receptor associated with that sensing array 80 as an integrated analysis circuit. Can be interpreted by IC.

FIG. 17 provides an array, generally indicated at 100, in a conductive sandwich grid configuration. A plurality of top electrodes TE (top electrodes) are arranged orthogonal to a plurality of bottom electrodes BE (bottom electrodes) to form the conductive grid 100. A test site TS (test site) is designated by each position where TE and BE cross. The plurality of nanoparticles QD are arranged between the electrodes TE and BE at each site TS. As shown in detail in FIG. 17B, an insulator I, such as multiple ligands, is provided to perform the function of the double tunnel junction. At each test site TS, one of the electrodes TE or BE functions as a source electrode and the other electrode functions as a drain electrode. result,
Each test site TS effectively comprises a single SET transistor. Each transistor or each group of transistors comprises a different binder, so that the conductive grid 100 may comprise a number of test sites TS designed to detect a number of different analytes.

In FIG. 18, a back gate type SET transistor (denoted by reference numeral 110) (
back-gated SET transistor) is provided. The source electrode S and the drain electrode D are sandwiched between the upper insulating substrate 112 and the lower insulating substrate 114. The nanoparticles QD and the capping ligand or other material I are placed in a well 116 formed between the source electrode S and the drain electrode D. The metal layer 118 is disposed on the nanoparticles QD and forms the base of the chemically operated gate of the SET transistor 110. A plurality of molecular recognition elements A are attached to the metal 118, whereby the SET transistor 1 for the binding event with the target detected substance B is obtained.
The sensitivity of 10 is increased. As with the other embodiments disclosed herein, the presence of non-target species C does not affect the IV characteristics of SET transistor 110 at all.

In FIG. 19, a SET probe 120 that enables scanning of the test surface 122 is provided by the inventor. The nanoparticles QD are attached to the probe tip 124 using the appropriate ligand L. The probe tip 124 is platinum-iridium (P
r-Ir) chip may be used. The magnitude of the change in the IV characteristics of SET probe 120 will depend on the presence of certain molecules or radicals present on test surface 122. For example, the response of probe 120 in the presence of methane (CH ₃ ) is different than the response in the presence of hydroxide (OH). Using known calibration data, the surface scan performed by the probe tip 120 will generate information that may be rasterized to produce an image representing the chemical signature of the test surface 122. . Molecular receptors may be attached to either the nanoparticle QD or the ligand L to scan a particular substance.

In some cases, the inventors have found that SET-based chemosensors can be constructed with gates that require additional detector-specific binding agents to work well. The pH-dependent sensor 60 in FIG. 10 is an example. Another example is the embodiment shown generally at 130 in FIG. 20, which may be used as a carbon monoxide detector. A platinum layer 132 (for example, 5 nm) is arranged on an insulating substrate SUB such as n-type silicon. Fine platinum wire (approx. 1 nm x 10 nm x depth 5 nm
) Is oxidized to platinum oxide (PtO) in a water / H ₂ SO ₄ medium using STM tips to define isolated platinum islands QDs (ie, metal or quantum dots). As a result, a Pt-PtO-Pt nanoparticle-PtO-Pt type double tunnel junction J is formed. The metal region on the outside is the source electrode S and the drain electrode D.
Play a role as. The CO detector 130 is sensitive to the presence of CO. This is because Pt-CO absorption occurs at the Pt island, which modifies the IV characteristics of the SET transistor. By generalizing this approach, similar sensors can be constructed. That is, several metal / metal oxide combinations (eg, Ti or Sn) that bind to small molecules of interest in chemical sensing are possible.

As described above, an electron for sensing a chemical substance and / or a biological substance, in which a transducer element operates in response to a single-electron transfer phenomenon and is considerably sensitive to a molecular binding event. The device is provided. The device can be built using the self-assembly method, is extremely small and consumes very little power. The sensitivity, selectivity, accuracy and other properties of this SET-based device are superior to conventional FET-based devices. A large number of these devices can be integrated on a single chip or substrate and can be used with a wide variety of sensing systems.

It will be appreciated that various details of the invention may be changed without exceeding the scope of the invention. Furthermore, the above description is for descriptive purposes only and not for limitation purposes. The invention is defined by the claims which come within the scope of the following claims.

[Brief description of drawings]

1A and 1B   It is a perspective view of the conventional field effect transistor.

[Fig. 2]   It is a top view of a single electron transistor.

3A and 3B]   FIG. 3 is an electric circuit diagram showing the operation of the single electron transistor of FIG. 2.

4 shows a plot of current versus voltage representing the electrical response of the single electron transistor of FIG.

FIG. 5 is a schematic diagram of an apparatus used to measure the electrical response of octanethiol ligand stabilized gold nanoparticles.

6A and 6B are plots of current versus voltage representing the electrical response of the gold nanoparticles of FIG. 5 for different pH values.

FIG. 7 is a schematic of the device used to measure the electrical response of gold nanoparticles stabilized with a galvinol ligand.

FIG. 8 is a chemical diagram showing conversion of galvinol to galvinoxide.

9A-9D are plots of current versus voltage representing the electrical response of the gold nanoparticles of FIG. 7 for different pH values.

[Figure 10]   FIG. 3 is a side view of a single electron transistor according to the present invention.

FIG. 11   FIG. 6 is a side view of another single electron transistor according to the present invention.

12A and 12B are plots of current versus voltage representing the electrical response of the single electron transistor of FIG. 11 in current and potentiometric detection methods, respectively.

[Fig. 13]   FIG. 12 is a diagram showing an example of the operation of the single electron transistor of FIG. 11.

14A and 14B show specific plots of current versus voltage and current versus time, respectively, showing the behavior of the single electron transistor of FIG. 11 when operating as shown in FIG. It is a figure.

FIG. 15   1 is a schematic diagram of a single electron transistor including an array of nanoparticles according to the present invention.

FIG. 16 is a plan view of a biochemical sensing device including a plurality of single electron transistors according to the present invention.

FIG. 17A is a perspective view of a biochemical sensing device according to the present invention including a plurality of single electron transistors arranged in a grid pattern of test sites.

FIG. 17B   FIG. 17B is a detailed side view of a test site for the device of FIG. 17A.

FIG. 18   FIG. 6 is a side view of another single electron transistor according to the present invention.

FIG. 19   1 is a perspective view of a single electron transistor based scanning probe according to the present invention.

FIG. 20   FIG. 6 is a perspective view of another single electron transistor according to the present invention.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI Theme code (reference) G01N 27/30 301N (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI) , FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN , TD, TG), AP (GH, GM, KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CR, CU, CZ, DE, DK, DM, DZ, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC , LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, UZ, VN, YU, ZA, ZW (72) Inventor Bruceau, Louis Sea, The Third, North Carolina, USA 27607, Raleigh, Oberry Street 1/2 2811

Claims (26)

[Claims] 1. A chemically-gated single-electron transistor having predetermined current-voltage characteristics and adapted for use as a chemical or biological sensor operable at room temperature, comprising: (a) a first A substrate formed of the insulating material of (1), (b) a source electrode arranged on the substrate, (c) a drain electrode arranged on the substrate, and (d) the source electrode and the drain electrode. A metal nanoparticle having a spatial dimension of about 12 nm or less, which is disposed between: (e) a target substance that is a target substance-specific binding agent that is located on the surface of the nanoparticle. A chemically-gated single-electron transistor comprising a detectable substance-specific binding agent, the binding event of which causes a detectable change in the current-voltage characteristic. 2. Further comprising a second insulating material attached to the surface of the nanoparticles,
The single-electron transistor according to claim 1, wherein the analyte-specific binding agent is attached to the second insulating material. 3. The single electron transistor of claim 1, wherein the nanoparticles have a spatial dimension of about 10 nm or less. 4. The nanoparticles are formed of gold.
Single electron transistor according to. 5. The single electron transistor of claim 1, wherein the nanoparticles are formed of silver. 6. The single electron transistor of claim 1, wherein the nanoparticles are formed of platinum. 7. A voltage source configured to apply a fixed bias potential, the voltage source being substantially stepped by a binding event occurring between a target analyte and the binder. The single-electron transistor of claim 1, wherein the change is caused. 8. A current source further configured to apply a fixed current,
The single-electron transistor of claim 1, wherein a binding event that occurs between a target analyte and the binder causes a substantially step change in voltage between the nanoparticles and the electrode. 9. A substrate to be insulated, which has predetermined current / voltage characteristics, a source electrode arranged on the substrate, a drain electrode arranged on the substrate, the source electrode and the drain electrode. An array of metal nanoparticles each having a spatial dimension of about 12 nm or less, disposed between the electrodes, and the current / voltage caused by a binding event occurring between the target analyte and the one or more nanoparticles. A sensing device for sensing a chemical or biological substance, comprising a transistor comprising a detectable substance-specific binding agent disposed on the surface of each nanoparticle that causes a detectable change in the property. . 10. A voltage source coupled to the source electrode and the drain electrode is communicated with the single-electron transistor to change a current-voltage characteristic of the single-electron transistor caused by the occurrence of the coupling event. The sensing device of claim 9, further comprising an integrated circuit configured to interpret. 11. The method according to claim 9, further comprising an insulating medium attached to the nanoparticles.
Sensing device described in. 12. The sensing device according to claim 9, wherein the binder is attached to a portion of the insulating medium corresponding to each nanoparticle. 13. (a) A single-electron transistor, each having a predetermined current / voltage characteristic, comprising an insulating substrate, a source electrode disposed on the substrate, and a drain electrode disposed on the substrate. A metal nanoparticle having a spatial dimension of about 12 nm or less arranged between the source electrode and the drain electrode, and a substance to be detected-specifically bound to the surface of each nanoparticle. A plurality of single-electron transistors that include a detectable change in current-voltage characteristics due to a binding event that occurs between the target object and each nanoparticle, and (b) a voltage source that communicates with the single-electron transistor. And (c) an integrated circuit configured to communicate with the single-electron transistor to interpret changes in current-voltage characteristics of the single-electron transistor caused by the occurrence of the coupling event. Sensing device for sensing a chemical or biological substance formed by including. 14. The sensing device according to claim 13, further comprising an insulating material attached to the surface of each nanoparticle, and the analyte-specific binding material attached to the insulating material. 15. The sensing device of claim 13, wherein each single electron transistor comprises a plurality of nanoparticles arranged between the source electrode and the drain electrode. 16. Each single-electron transistor includes a binder that is different than the binder of the other single-electron transistor, each binder being configured to receive a different target analyte, and the integrated circuit comprising: It is configured to interpret the change in the current-voltage characteristic of each single-electron transistor based on the predetermined reference current-voltage characteristic and the address of the single-electron transistor to distinguish the response of each single-electron transistor. Claim 13
Sensing device described in. 17. The plurality of single-electron transistors are divided into a plurality of groups of single-electron transistors, and the single-electron transistors belonging to each group are different from the binder of the single-electron transistors belonging to other groups. The integrated circuit is configured to detect different target analytes including an agent, and the integrated circuit includes a single electron transistor belonging to each group based on a predetermined reference current-voltage characteristic and an address of the single electron transistor belonging to each group. 14. An arrangement adapted to interpret changes in the current-voltage characteristics of electronic transistors to distinguish the response of single-electron transistors in each group.
Sensing device described in. 18. A sensing device for sensing a chemical substance or a biological substance, comprising: (a) a substrate to be insulated; and (b) a plurality of elongated strips spatially spaced from each other on the substrate. A lower electrode, and (c) spatially spaced from each other on the lower electrode so as to cross the lower electrode, and in cooperation with the lower electrode, a single electrode is provided between the lower electrode and the lower electrode. A plurality of elongated upper electrodes forming a grid pattern including a plurality of intersecting regions defining test sites, and (d) each having a prepared reference current-voltage characteristic, and said upper part at each of said test sites. Metal nanoparticles having a spatial dimension of 12 nm or less arranged between an electrode and the lower electrode, stabilized by an insulating medium, and having a target substance-specific binding agent arranged on the surface thereof. A single-electron transistor built at each test site, where a binding event occurring between the target analyte and the nanoparticle causes a detectable change in the current-voltage characteristics of the nanoparticle; ) A voltage source communicating with the upper electrode and the lower electrode, and (f) communicating with the test site to interpret the change in the current-voltage characteristic of the single electron transistor caused by the occurrence of the binding event. And a sensing device including the integrated circuit configured as described above. 19. The sensing device of claim 18, wherein the binder of each single electron transistor is attached to the insulating medium. 20. Each single-electron transistor includes a binder different from the binders of other single-electron transistors and each configured to receive a different analyte, said integrated circuit comprising: It is configured to interpret the change in the current-voltage characteristic of each single-electron transistor based on a predetermined reference current-voltage characteristic and address of each single-electron transistor to distinguish the response of each single-electron transistor. The sensing device according to claim 18, 21. The test site is divided into a plurality of groups of test sites, and the single electron transistors belonging to each group of test sites include a binder different from the binder of the single electron transistors belonging to other groups. The integrated circuit interprets the change in the current / voltage characteristics of the single-electron transistors of each group based on the predetermined reference current / voltage characteristics and the address of the single-electron transistors of each group, and 19. The sensing device of claim 18, configured to distinguish the response of a one-electron transistor. 22. A chemically gated single-electron transistor having predetermined current-voltage characteristics and adapted for use as a chemical or biological sensor operable at room temperature, comprising: (a) a bottom insulation. A substrate, (b) an intermediate metal layer disposed on the lower insulating substrate, and (c) an upper insulating substrate having a source electrode on a first portion of the intermediate metal layer,
An upper insulating substrate in which a well defining a drain electrode in the second portion of the intermediate metal layer is formed in the intermediate metal layer and the upper insulating substrate; and (d) on the well and on the upper insulating substrate. (E) metal nanoparticles located in the well, having a spatial dimension of about 12 nm or less and being stabilized in an insulating medium; ) A molecular gate attached to the surface of the upper metal layer, which comprises a target substance and a binding event occurring between the target substance and the target substance causing a detectable change in current-voltage characteristics. A single-electron transistor that operates. 23. The single electron transistor of claim 22, further comprising a plurality of molecular acceptors attached on the surface of the upper metal layer. 24. A single electron transistor probe configured to scan a surface for the presence of chemicals or biologicals, comprising: (a) a conductive probe tip; (b) 12 nm or less. (C) Detection of current / voltage characteristics by a binding event that occurs between a metal nanoparticle having a spatial dimension and attached to the probe chip via an insulating medium, and (c) a target attached to the nanoparticle. A single-electron transistor probe comprising a detectable substance-specific binding agent that produces a possible change. 25. A single electron transistor device operable at room temperature and having predetermined current-voltage characteristics useful for sensing chemicals, comprising: (a) a substrate formed from a first insulating material. (B) a metal layer disposed on the substrate, (c) formed in a region of the metal layer, and including an oxide of the metal layer,
The metal layer has a first region that defines a source electrode, a second region that defines a drain electrode, and a binding event with a target molecule that causes a detectable change in current-voltage characteristics of about 12 nm or less. Third defining metal nanoparticles with spatial dimensions
And an insulator that realizes a double tunnel junction. 26. The method of claim 25, wherein the metal layer is platinum, the insulator comprises platinum oxide, and absorption of carbon monoxide in the nanoparticles causes a detectable change in current-voltage characteristics. Single electron transistor.