WO2004044179A2

WO2004044179A2 - System and method for remote interrogation motion detection

Info

Publication number: WO2004044179A2
Application number: PCT/US2003/036278
Authority: WO
Inventors: Lars Chapsky; Rodolfo E. Diaz; Michael Watts
Original assignee: Arizona Board Of Regents
Priority date: 2002-11-08
Filing date: 2003-11-10
Publication date: 2004-05-27
Also published as: AU2003290832A8; AU2003290832A1; WO2004044179A3

Abstract

A system and method are provided for detecting at least one of a particular type of molecule. The system (100) includes at least one antenna element and a number of metallic elements. The antenna element (140) is capable of creating a radiation distribution if a radiation source directs radiation toward the at least one antenna element. Each of the antenna elements include a molecular motor (180) positioned adjacent to the antenna element and a trapping armature (120) associated with a first trapping template (170). The first trapping template is configured to bind with a first portion of the at least one of the particular type of molecule (130) and each of the metallic elements (110) are associated with a second trapping template (190) configured to bind with a second portion of the at least one of the particular type of molecule. The molecular motor moves the trapping armature such that, if the first trapping template has bound the first portion of a molecule and the second trapping template has bound the second portion of the same molecule, the metallic element disrupts the radiation distribution associated with the at least one antenna element.

Description

SYSTEM A D METHOD FOR REMOTE INTERROGATION MOTION DETECTION

SPECIFICATION

FIELD OF THE INVENTION The present invention relates to methods and systems for motion detection by remote interrogation. More particularly, the present invention relates to methods and systems for nanoscale particle motion detection by remote interrogation.

BACKGROUND OF THE INVENTION The practice of identification of molecular species such as DNA strands and hazardous bioagents through the detection of complexes of such molecules with templates of high specificity is an area of growing interest both in pure research and in commercial, security applications. Present identification methods are time consuming and suffer from low throughput. For example, a practice to identify a given DNA strand is to expose a DNA-containing solution to a template containing its Watson-Crick complement and thus trap the target DNA through a hybridization reaction. This trapping step is then followed with purification, and Polymerase Chain Reaction (-PCR) amplification steps to produce enough molecular material to detect the presence or absence of the target. The time required to perform these subsequent chemical reactions typically generally exceeds the time required for the initial trapping of the molecule with the template by several orders of magnitude. Accordingly, an inspection method is needed that does not require large amounts of molecular material for effecting the measurement and that allows molecular identification applications to proceed in real time. SUMMARY OF THE INVENTION

An object of the present invention is to provide a method and system for detection motion by a remote interrogation. A further object is to provide a method and system for detecting a particular molecule. The foregoing objects are attained, in accordance with the present invention, by a system for detecting at least one of a particular type of molecule. The system includes at least one antenna element and a number of metallic elements. The antenna element capable of creating a radiation distribution if a radiation source directs radiation toward the at least one antenna element. Each of the antenna elements include a molecular motor positioned adjacent to the antenna element and a trapping armature associated with a first trapping template. The first trapping template is configured to bind with a first portion of the at least one of the particular type of molecule. Each of the metallic elements are associated with a second trapping template configured to bind with a second portion of the at least one of the particular type of molecule. The molecular motor moves the trapping armature such that, if the first trapping template has bound the first portion of a molecule and the second trapping template has bound the second portion of the same molecule, the metallic element disrupts the radiation distribution associated with the at least one antenna element. For a better understanding of the invention, reference may be made to the following description of an exemplary embodiment, taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS A more complete understanding of the present invention may be obtained from consideration of the following descriptions, in conjunction with the drawings, of which:

Fig. 1 is a diagram of a device according to the invention for motion detection by remote interrogation; Fig. 2a is a diagram of an exemplary embodiment of an antennae array for use with the device shown in Fig. 1; Fig. 2b is a diagram of an exemplary embodiment of the antennae array illustrated in Fig. 2a showing a direction of an interrogating electromagnetic wave;

Fig. 3 is a diagram showing a three-dimensional representation of a diffraction pattern that can be provided by the array illustrated in Fig. 1 ;

Fig. 4 is a representation of the antennae array of Fig. 1 having a metal nanosphere creating a perturbation of the field;

Fig 5 is a diagram showing a three-dimensional representation of a diffraction pattern that can be provided by the array illustrated in Fig. 1 having a field perturbation, as shown in Fig. 4;

Fig. 6a is a diagram of a polar view of the diagram shown in Fig. 3;

Fig. 6b is a diagram of a polar view of the diagram shown in Fig. 5;

Fig. 7 is a plot diagram of an array pattern of an embodiment of the device shown in Fig. 2 when a particle passes through one element; and Throughout the figures, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components or portions of the illustrated embodiments.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In order to solve the aforementioned problems, a method and device for detecting motion by a remote interrogation is provided using an array of antennae elements and an interrogating electromagnetic field.

An exemplary embodiment of a particle motion detection system 100 in accordance with the invention is shown in Fig. 1 for trapping and detecting at least one molecule. A system 100 in accordance with the present invention includes at least one metal nanosphere 110, a remote antennae portion 140, with a first trapping template 190 for connecting the remote antennae portion 140 to the molecule to be detected 130.

As shown in Fig. 1, the system 100 includes a metal nanosphere portion 110, having a first trapping template 190 connected thereto for trapping small particles. The metal nanosphere portion 110 is dimensioned such that it is capable of being detected by a nanoscale particle detector. For example, metal nanospheres are detectable using nanoscale particle detectors such as those described below. Each nanosphere is provided with a first trapping template 190 for trapping a portion of a molecule to be detected 130. In one exemplary embodiment of the present invention, gold nanospheres can be provided having dimensions of about 2-20 nm in diameter. The trapping template 190 can be ligands such as thiolated cyclodextrin receptors which are bonded to the sphere antennae portions 110.

Accordingly, the nanospheres and their ligand receptors form nanoparticles that can engage in host-guest interactions with guest molecules. These nanoparticles can be provided in an aqueous solution or other solution that permits interaction between ligand receptors and target molecules. Methods of providing trapping templates 190 have been described by Liu et al. in "Cyclodextrin-Modified Gold Nanospheres", Langmuir 2000, 16, 3000-3002; and by Liu, et al. in "In Situ Modification of the Surface of Gold Colloidal Particles Preparation of Cyclodextrin- Based Rotaxanes Supported on Gold Nanospheres", Langmuir 1998, 14, 7337-7339. These documents are incorporated herein by reference in their entirety. In addition, the system 100 is provided with at least one complementary trapping armature 120 as shown in Fig. 1. The complementary trapping armature 120 includes a second receptor 170 for providing a complementary binding site to trap another portion of the target molecule 130 to be detected. The trapping armature 120 includes an electro/chemomechanical machine 180 (e.g., a molecular motor) for providing movement of the second receptor 170. The electromechanical machine 180 can be a molecular motor with an armature such as described by Carlo Montemagno and George Bachand in "Constructing nanomechanical devices powered by biomolecular motors", Nanotechnology 10, (1999) 225-231. This document is also incorporated herein by reference in its entirety. For example, a 12 nm ATPase protein motor can be used to provide a pivot point for this armature. However, the electromechanical machine 180 is not limited to ATPase motors, but includes other mechanical moving devices that can be fabricated on a small scale. In one exemplary embodiment of the present invention, the system 100 is provided as a wave interrogated resonant array. Such wave interrogated incident array includes an incident electromagnetic energy source 160 for providing an electromagnetic field directed at (e.g., incident to) a resonant array of antennae elements 140. An electromagnetic energy source 160 can include laser devices for providing radiation having wavelengths appropriate to produce a diffraction pattern when the laser energy illuminates the resonant array of antennae elements 140. The array is provided so that a designed periodicity permits a characteristic reflection signature consisting of a specularly reflected beam and one or more designed diffracted orders. The diffracted energy can be effectively filtered through a holographic arrangement provided for a detection of variations.

Fig. 2 shows an example of an array of antennae elements 140. Each antennae element 140 is a pair of 45-degree (half-angle) metal bowties with a feed gap. The feed gap having a sufrace area equal to approximately ( λ / 9.6)². Each antennae element 140 is spaced λ apart from another such antennae element 140 in an embodiment, and is illuminated at θ_inc = 30° . At least one complementary trapping armature 120 is provided substantially near the feed gap (sometimes called the feed) of at least one antennae. When one of the antennae elements 140 of the array is perturbed by the motion of a complementary trapping armature 120, the periodicity of the array is compromised and the diffracted orders may bring the metal nanosphere into the proximity of an antenna feed. This change can be represented by a very strong signal in the holo graphically filtered signature of the array. The resonant nature of the antennae elements 140 provided in an array typically makes them extremely sensitive to sub-wavelength objects. Sub-wavelength objects are objects that would normally be undetectable with direct plane wave illumination. The open- feed antennae elements 140 can thus operate at least down to optical wavelengths (such as 633 nm) and may detect dielectric objects at least as small as 40 nm.

The array of the antennae elements 140 is constructed on a substrate 150 that can be prepared for the deposition of small electomechanical machines such as molecular motors 180. Molecular motors 180 can be ATPase molecular motors deposited over the array at such a density to ensure that one or more of the antennae elements 140 have motors 180 close to their open feed. In one exemplary embodiment of the present invention, motors 180 are provided within 60 nm of the open feed, but can also be provided at other distances depending on the expected length of moving structures such as ligands and target molecules. In another exemplary embodiment of the present invention, each electromechanical machine 180 is provided with an armature 120 for movement about an axis of the motor 180. Each electromechanical machine 180 can be provided to drive the armature along at least a portion of an arc or circle around the electromechanical machine 180. Alternatively, an electromechanical machine 180 can be provided to permit the armature to rotate freely over at least a portion of an arc or circle around the electromechanical machine 180 when subjected to the influence of an external field. For example, a magnetic field can cause a magnetically inducible armature or an armature connected to a magnetically inducible nanoparticle to rotate in the direction of the arc around the electromechanical machine. Each armature 120 is provided with a second receptor 170 having affinity for one end of the target molecule 130. The second receptor 170 can be ligand adapted to provide the particular affinity for target molecule 130. In an exemplary embodiment of the present invention, metal nanospheres will be prepared that have an affinity to the target molecules 130. The second receptor 170 may have an affinity to one end of the target molecule 130, and the metal nanosphere can have an affinity for the other end. As a result of the metal nanosphere's affinity to the target molecule 130, if a sample of target molecules 130 is inserted into a fluid containing the nanospheres, the target molecules 130 may become attached to the nanospheres. If this fluid is also provided in contact with the first trapping templates 190 of the array, target molecules 130, which are attached to the metal nanospheres, can become affixed to the electromechanical machines 180.

The array and the fluid are remotely interrogated with a laser to generate a baseline diffraction pattern. The baseline diffraction pattern is likely to differ from an unperturbed array without the fluid because the presence of nanospheres at various places in the neighborhood of the antennas is expected to perturb many of antennae. However, because the diffraction pattern results from coherent illumination of a periodic array of elements, it tends to have a well defined pattern of maxima and minima as a function of angle in space. With the use of an array of photodetectors, a CCD camera, or an opaque screen, an individual would be able to see this pattern. When a target molecule 130 such as ATP is introduced into the solution, the electromechanical machines 180 begins to turn. In combination, when the fluid having sample molecules and nanospheres is provided in contact with the array, the target molecules 130 will attach themselves to the nanospheres at one end, and to the second receptor 170 at the other end. The motors 180 that are connected to the second receptors 170 which have the captured target molecules 130 may also have nanospheres captured at an opposite end of the target molecules 130. The captured nanospheres are pulled by the electromechanical machines 180 due to the connection through the target molecule 130, through the near-fields of the open- feed antennas, and periodically perturb the field of the interrogating beam. This results in a readily detectable flicker in the diffraction pattern of the array. If the nanospheres do not contain any target molecules 130 or if the second receptors 170 of the electromechanical machines 180 do not attract and capture target molecules 130, the nanospheres do not attach to the electromechanical machines and thus there will be no motion of nanospheres to cause a flicker. The antennae elements 140 can be very sensitive to molecular perturbations by providing the antennae with a sensitive resonant characteristic. In an exemplary embodiment of the invention, each antennae element 140 is a pair of micro-structures in a bowtie arrangement which concentrate the incident field of the interrogating laser from an area of the order of (λ/2)² down to an area of the order of (λ/16) or less near the feed of the antennae elements 140. As a result, the electric field at the feed of the antenna elements 140 can exceed the field strength of the incident wave by an order of magnitude. If a foreign object, such as a nanosphere, is present near the feed of one of the elements of the array, it is illuminated by the amplified fields of the interrogating laser and reradiates portions of the radiation back onto an element of the antennae. The element, in turn, re-radiates the radiation back into the free space which radiation is thus out of phase with the radiation reflection pattern created by the rest of the elements of the array.

It is preferable for the perturbing objects to be brought into the plane of the array to facilitate a greater diffraction response. For instance, a two-element interferometer (as shown in Fig. 2) can include two antennae elements 140. For example, the elements can be spaced 1.0 λ apart, and illuminated so as to form an interrogating laser at 30 degree incidence. One element can exclude electromechanical machines 180 to remain unperturbed as a reference element, and the second element can be provided in the electromechanical machine 180 and first trapping template 190 as described above to allow for the capturing of a nanosphere in the presence of a target molecule 130. If the antennae elements 140 have a similar configuration, their scattering signals can cancel each other in a direction normal to their plane.

Fig. 3 shows a graphical representation of a far-field radiation distribution over a hemisphere above the antennae elements 140 illustrated in Fig. 2. This distribution can be calculated using a full-physics solution of Maxwell's equations known as Finite Difference Time Domain method (FDTD). The dark line in the plane of symmetry of the elements shows cancellation of reradiated radiation. Thus, a photodetector located directly above the antennas and in the symmetry plane could be provided to detect very low intensity radiated signals.

When a metal nanosphere is brought into the open- feed gap of one of the antennae elements 140 by the motion of the electromechanical machine 180, it can alter the phase response of that antenna such that the direction of signal cancellation shifts, thereby creating a clear signal for a photodetector to detect a difference to the baseline measurement.

Figs. 4 - 7 show the result of the full-physics simulation when a perturbation exists in the open-feed gap of the antennae element 140. Fig. 4 illustrates a metal nanosphere in the open-feed gap of the antennae element 140. Fig. 5 shows a full-physics solution for the case when the top bowtie is perturbed by the particle. The symmetry is broken, and there is no longer a null-signal at a detector located in the place of symmetry. Fig. 6a shows a top view of the far-field radiation hemisphere with no nanosphere perturbing a bowtie. Fig. 6b shows a view of the far-field radiation with a perturbed bowtie. Fig. 7 shows a plot of the power density as a function of angle from normal on the two-principal planes of the proposed set-up. The plane of symmetry is the phi=0 degree plane. The signal obtained by a detector located directly above the antennas on the plane of symmetry of the perturbed array is 20% of the maximum scattered power by the unperturbed array. A confirmation of the detection of the sphere can be provided to occur periodically as the electromechanical machine 180 rotated, and the perturbation signal is created on each revolution. An alternative embodiment of an array pattern of the system 100 shown in Fig. 1 may include a micro fmidic channel. The system 100 can be provided with a microfluidic channel connecting the feeds of at least two antennae elements 140. hi such a configuration, metal nanospheres moving through the channel can be detected as they cross the feed regions of the antennas. A related precursor device is a Coulter Counter described in O. A. Saleh and L. L. Sohn, "Quantitative sensing of nanoscale colloids using a microchip Coulter counter", Review of Scientific Instruments, 72 (12) pp. 4449-4451, December 2001 the entire disclosure of which is incorporated herein by reference.

Alternative embodiments of remotely interrogated nanoscale motion detectors according to the present invention can be provided utilizing other forms of MEMS and NEMS devices in combination with the bowtie antennae arrays. For example, the inclusion of the motion sensitive arrays on the same chip as a MEMS or NEMS device can be provided to allow for remote assessment of the static or dynamic state of a particular device. The device to be monitored is provided with a mechanical coupling. The mechanical coupling is provided proximate to the feed of an array for perturbing the near field of a detecting element. In this way a device can communicate its status to another device without carrying on board any optical or microwave signaling equipment.

Such detector is an advantageous over micromirrors by providing greater compactness. In addition, these antennae elements 140 can be carried by the moving portion of an individual MEMS or NEMS device. Accordingly, a correlation of the interference between a stationary antennae and an antenna on a moving MEM or NEM device could be used to track the position of the moving portion of the device to within 25 nm.

The invention is not limited to ATPase motors, nor is the invention limited to the embodiments described in detail herein.

Claims

CLAIMS 1. A method for detecting at least one particular type of one or more molecule, comprising the steps of:

(a) providing first and second elements, each being configured to bind with the one or more molecule;

(b) measuring a radiation distribution associated with the first and second element; and

(c) detecting a change in the radiation distribution which indicates a presence of the one or more molecules.

2. The method of claim 1, wherein the first element includes a molecular motor and a trapping armature associated with a first trapping template configured to bind with a first portion of the at least one of the particular type of molecule.

3. The method of claim 2, wherein the trapping armature is connected to the one of the at least one second element.

4. The method of claim 1, wherein the second element includes a metallic element associated with a second trapping template configured to bind with a second portion of the at least one of the particular type of molecule.

5. The method of claim 1, wherein the step (c) further includes the steps of: moving the second element such that, if the first element has bound the one or more molecule and the second element has bound the one or more molecule, the first element disrupts the radiation distribution; and detecting the disruption of the radiation distribution which indicates a presence of the one or more molecules.

6. The method of claim 1 , wherein the detecting arrangement includes at least one antenna element capable of creating a radiation distribution if a radiation source directs radiation toward the at least one antenna element.

7. A system for detecting at least one particular type of one or more molecules, comprising: at least one first and at least one second elements, each being configured to bind with the one or more molecule; a detecting arrangement, wherein the detecting arrangement measures a radiation distribution associated with the at least one first and at least one second element and is configured to detect a change in the radiation distribution which indicates a presence of the one or more molecules.

8. The system of claim 7, wherein the detecting arrangement includes at least one antenna element capable of creating a radiation distribution if a radiation source directs radiation toward the at least one antenna element.

9. The system of claim 8, wherein each of the at least one antenna element includes: one of the at least one second element; and a trapping armature associated with a first trapping template configured to bind with a first portion of the at least one of the particular type of molecule, wherein the trapping armature is connected to the one of the at least one second element.

10. The system of claim 9, wherein the one of the at least one second element is a molecular motor.

11. The system of claim 10, wherein the molecular motor is positioned adj acent to the antenna element.

12. The system of claim 9, wherein each of the at least one first element includes a metallic element associated with a second trapping template configured to bind with a second portion of the at least one of the particular type of molecule.

13. The system of claim 9, wherein the at least one second element moves the trapping armature such that, if the first trapping template has bound the first portion of a particular molecule and the second trapping template has bound the second portion of the particular molecule, the metallic element disrupts the radiation distribution associated with the at least one antenna element indicating the presence of the at least one of the particular type of molecule

14. A system for detecting at least one of a particular type of molecule, comprising: at least one antenna element capable of creating a radiation distribution if a radiation source directs radiation toward the at least one antenna element, each of the at least one antenna element including: a molecular motor cooperating with the antenna element; and a trapping armature associated with a first trapping template configured to bind with a first portion of the at least one of the particular type of molecule, wherein the trapping armature is connected to the molecular motor; and a plurality of metallic elements, each of the plurality of metallic elements associated with a second trapping template configured to bind with a second portion of the at least one of the particular type of molecule, wherein the molecular motor moves the trapping armature such that, if the first trapping template has bound the first portion of a particular molecule and the second trapping template has bound the second portion of the particular molecule, the metallic element disrupts the radiation distribution associated with the at least one antenna element indicating the presence of the at least one of the particular type of molecule.