WO2006107972A2 - Capteur utilisant la permittivite - Google Patents

Capteur utilisant la permittivite Download PDF

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WO2006107972A2
WO2006107972A2 PCT/US2006/012512 US2006012512W WO2006107972A2 WO 2006107972 A2 WO2006107972 A2 WO 2006107972A2 US 2006012512 W US2006012512 W US 2006012512W WO 2006107972 A2 WO2006107972 A2 WO 2006107972A2
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capacitor
detection
approximately
coupled
fluidic
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WO2006107972A3 (fr
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Andreas Wankerl
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Cornell Research Foundation Inc
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Cornell Research Foundation Inc
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N22/00Investigating or analysing materials by the use of microwaves or radio waves, i.e. electromagnetic waves with a wavelength of one millimetre or more
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54373Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • G01N33/5438Electrodes

Definitions

  • a device includes a splitter that splits a time varying signal into two substantially equal power signals.
  • a reference capacitor having a fluidic channel between capacitor plates is coupled to one of the equal power signals and a detection capacitor having a fluidic channel between capacitor plates is coupled to the other of the equal power signals.
  • a detector is coupled to outputs of the reference capacitor and detection capacitor. The signals are approximately 180 degrees out of phase with each other when combined before or at the detector, plus whatever shift may be introduced in the detection capacitor.
  • the device is formed of microstrip circuit or co-planar waveguide circuits, and operates a microwave frequencies.
  • FIGs. IA, IB and 1C depict a conceptual schematic of the differential detection circuit with detection chambers containing covalently bound probes with and without the occurrence of a binding event.
  • FIG. 2 shows a cutaway view of an example arrangement of a reference chamber and a detection chamber.
  • FIGs. 3A, 3B and 3C detail top, cross-sectional and end-on views, respectively, of a fluidic channel passing through a capacitor (C ref) of a reference chamber and the capacitor (C det ect) of a detection chamber aligned in a series.
  • FIGs. 3D, 3E and 3F detail top, cross-sectional and end-on views, respectively, of two fluidic channels arranged in parallel, each passing through a reference and a detection chamber. 1153.129WO1 2 [0009] FIG.
  • FIG. 4A details a' top view of an alternative arrangement where a fluidic channel passes through the capacitor (C re f) of a reference chamber and the capacitor (C dete ot) fa detection chamber placed across the fluidic channel in parallel so that both chambers are exposed to the sample at the same time.
  • FIG 4B details a top view of an alternative arrangement where two separate fluidic channels pass through the capacitor (C re f) of a reference chamber and the capacitor (C detect ) of a detection chamber.
  • FIGs. 4C and 4D detail top and cross-sectional views of an example embodiment that uses semiconducting or insulating pillars arranged between the chambers to regulate the flow speed of the sample through the channel.
  • FIGs. 5A and 5B show complex permittivity spectra of water and horseradishperoxidase solutions according to an example embodiment.
  • FIG. 6 is a block diagram of simulated microwave circuit according to an example embodiment.
  • FIG. 7 is a transmission profile as a function of frequency for the circuit of FIG. 6.
  • FIG. 8 is a transmission profile as a function of frequency for various configurations of ideal capacitors having various values according to an example embodiment.
  • FIGs. 9A, 9B, 9C and 9D illustrate a block circuit diagram with series inductance and corresponding transmission and frequency profiles according to an example embodiment.
  • FIGs. 1OA, 1OB, 1OC and 1OD illustrate a block circuit diagram with parallel inductance and corresponding transmission and frequency profiles according to an example embodiment.
  • FIG. 11 illustrates a corresponding output signal as a function of capacitance level according to an example embodiment.
  • FIG. 12 is a block diagram of a capacitive test cell formed according to an example embodiment.
  • FIG. 13 illustrates the phase behavior of impedances of test cells without cladding layers according to an example embodiment.
  • FIG. 14 illustrated the phase behavior of impedances of test cells with a parallel inductor and without cladding layers according to an example embodiment.
  • FIGs. 15A and 15B illustrate the phase behavior of impedances of test cells with a parallel inductor tuned to a resonance frequency of 7GHz according to an example embodiment.
  • FIG. 16 illustrates an impedance phase difference of test cells with a parallel inductor according to an example embodiment.
  • FIGs. 17A, 17B and 17C illustrate impedance magnitudes of parallel configurations for multiple example embodiments.
  • FIG. 18 illustrates changes in impedance magnitude for 90 degree contacting of water and solution capacitors according to an example embodiment.
  • FIG. 19 illustrates magnitudes of a final result of a fully simulated example circuit over a range of frequencies.
  • a method and apparatus for detecting the difference in dielectric pem ⁇ ttivity between two liquid media in a microfluidic system is described.
  • the presence of the two liquid media with different permittivity may arise from (1) the separate introduction of two liquid media with inherent different permittivity such as arising, for example, from the different concentrations of solutes or (2) a different temperature of identical liquid media at the time of measurement causing different permittivity or (3) a temporal difference in permittivity 1153.129WO1 4 between the two liquid media at the time of measurement as can be achieved, for example, with capillary electrophoresis or (4) a localized difference in permittivity as can be achieved, for example, by localized chemical or biological reaction of targets with probes immobilized in the detection area.
  • the first part of the description of method and apparatus focuses on one embodiment for detecting the presence of targets that may or may not be indicative of disease.
  • the presence of a target is identified by detecting a localized binding event that occurs between a target and a probe on electrode plates of a Capacitive Test Cell.
  • the probe and target may be any antigen or any cell or any nucleic acid or any chemical or any antibody or any receptor (e.g., antigen presenting MHC Class 2 receptor).
  • a design and simulation of microwave circuitry for carrying out the method and apparatus is then described, along with simulated results and discussion of current understanding of the operation of the design.
  • the design and simulation in the second part relies only on the input of a difference in permittivity, and is thus representative of more than just the embodiment described for detecting the presence of targets that may or may not be indicative of disease.
  • the prior art uses low frequencies to detect the changes in dielectric properties (typically low Hz or KHz) range. At low frequencies, the rearrangement of small ions contained in the surrounding solution and their interaction with the electrode plates are responsible for signal changes, hi the MHz frequency range, a change in the dielectric properties arises from the orientational relaxation of the protein dipoles. hi the high MHz to low GHz frequency range, the change in dielectric properties appears primarily due to the changed presence of free water and the orientational relaxation of the hydration shell (strongly bound water), which surrounds the protein, m one embodiment, the dielectric properties include the orientational relaxation of biological molecules, moieties of biological molecules, hydration shells of molecules and free water.
  • microwave frequencies are defined as in the range of approximately 300 MHz to 50GHz.
  • the range of microwave frequencies of most interest include approximately 1 GHz to 20 GHz, corresponding to significant microwave absorption by water.
  • Probes may comprise linker molecules that can be electrochemically attached to the surface while keeping the electrodes DC charged and using the same circuit as for the detection of high frequencies.
  • a linker molecule may be immobilized electrochemically on the surface of the electrode, and any number of prior or further chemical reactions may be performed in connection with the attachment of the probe.
  • the probe molecule may be reacted with the linker molecule.
  • This invention is significant in that it allows the chip structure to be manufactured independently of the probe attachment (thus making it cheaper by using standard microfabrication technology as used, for example, in the context of semiconductor manufacturing). It is furthermore significant in that it allows for the selective immobilization of different probes in one apparatus, allowing multiple targets of multiple diseases, diseases of multiple targets, or combinations thereof, to be integrated in one apparatus using the same sample containing the multiple targets.
  • FIG. IA depicts a conceptual schematic of a differential detection circuit 100 operating at microwave frequencies.
  • the detection circuit in FIG IA consists of a microwave signal source 110, the output of which is split into two equal signals via a splitter element 115 with one of the two signals being applied to a detection chamber or capacitor 120 and the other signal being applied to a reference chamber or capacitor 125 after being phase shifted 180 degrees by an inverter 130.
  • the signals are not phase shifted until after the respective chambers, but prior to or at recombination.
  • the presence of an analyte in one channel may introduce a further phase shift from 180 degrees which may be detected. In other words, the phase shift is 180 degrees, plus any additional phase shift introduced by differences in dielectric in the two capacitors.
  • the microwave signal source 110 may be a voltage controlled oscillator integrated with the device or a microwave signal coupled to the device 1153.129WO1 6 from an external source via an antenna.
  • the detection chamber 120, as well as the reference chamber 125 may comprise any identical sub-circuit, such as, for example, any resonant circuit, containing the detection and reference capacitor respectively.
  • each signal undergoes a near identical phase and amplitude modification in the absence of target to probe binding in the detection chamber 120.
  • the combination of the two signals using a combiner 135 will result in the two signals canceling each other.
  • This combined signal may be detected on-chip by detector 140, for example, after conversion by an RMS power detector as a near-zero DC signal, or transmitted to an external detector 140 with or without any kind of prior signal modification.
  • the detection chamber 120 contains covalently bound probes as indicated at 150 in FIG.
  • FIG. 1C depicts the contrasting scenario to FIG. IB, where the presence of a target triggers a binding event 160 in the detection capacitor.
  • the detection capacitor will change its capacitance but the reference capacitor will not, so that the amplitude and phase modification of its signal will differ from that of the reference capacitor.
  • the combination of the two signals will no longer cancel and the resultant combined signal will indicate the presence of the trigger.
  • the probes may be immobilized on one or both electrodes of the detection chamber 120 that forms the basis for measuring the capacitance of the content between the two electrodes.
  • the detection chamber 120 may be a component of a microfluidic channel through which the sample, containing the target, is introduced. The microfluidic channel extends prior to and following the detection chamber 120 in a continuous manner. The binding event is detected by measuring the change in capacitance that occurs as a result of said binding event.
  • Multiple detection chambers may be used to detect binding events, and contain covalently bound probes. Each detection chamber may be 1153.129WO1 7 paired with one or more "reference chambers".
  • a reference chamber differs from a detection chamber in that probes are not immobilized on either of the reference chamber's electrodes. Rather, "unreactive probes" may be immobilized on one or more of the reference chamber's electrodes. Unreactive probes are defined as being similar or identical in structure, and/or composition to probes, but without the correlative binding characteristics; ideally unreactive probes would encompass no correlative binding characteristics of the comparative probe.
  • the circuit element of the microwave detection circuit which is basis of the detection chamber, may be integrated on-chip with the fluidic channel and the surrounding capacitors.
  • FIG. 2 illustrates a cutaway view of an example embodiment 200 of a reference chamber and a detection chamber.
  • the diagram shows an example arrangement of the capacitor and micro fluidic channel in the on-chip integrated circuit for a given chamber.
  • the capacitor 125 for the reference chamber and the capacitor 120 for the detection chamber are arranged in series in the fluidic channel.
  • the separation of the capacitor electrodes of a given chamber is determined approximately by the height of the fluidic channel.
  • the dimensions of the capacitor electrodes and the height of the fluidic channel, along with any additional layers on the electrode surfaces facing the fluidic channel, may be designed in accordance with the frequency used to give capacitance values which optimize the signal to noise ratio of the detection circuit and which may make use of a resonant circuit design.
  • FIG. 2 also indicates a possible layout for connecting the capacitor electrodes to a coplanar wave guide 210. A different embodiment may use a microstrip layout (not shown in FIG. 2).
  • FIGs. 3A, 3B and 3C detail top, cross-sectional and end-on views, respectively, of an example fluidic channel 310 passing through the capacitor (C re f) of a reference chamber 125 and the capacitor (C detect ) of a detection chamber 120 respectively, aligned in a series.
  • FIGs. 3D, 3E and 3F detail top, cross-sectional and end-on views, respectively, of two fluidic channels 320, 330 arranged in parallel, each passing through reference chambers 335, 340 and corresponding detection chambers
  • an upper fluidic channel 320 is detecting the presence 1153.129WO1 8 of a target C and therefore passes through the capacitor (C re f) of reference chamber 335 and the capacitor (C detect ) of detection chamber 345.
  • the lower fluidic channel 330 is detecting for the presence of target D and therefore passes through the capacitor (D ref ) of reference chamber 340 and the capacitor (Ddetect) of detection chamber 350.
  • detection chamber arrangements for detecting multiple different targets does not rely on the chambers being arranged in parallel as they may also be arranged in series, and multiple further detection and reference chambers may be included.
  • the capacitor electrodes may consist of one or more conductive materials and the surface layer facing the channel may consist of either a metal, an insulator or a crystalline or polycrystalline or amorphous semiconductor.
  • FIG. 4A details a top view of an alternative arrangement where a fluidic channel 410 passes through the capacitor (C ref ) of a reference chamber 415 and the capacitor (C dete c t ) of a detection chamber 420 placed across the fluidic channel in parallel so that both chambers are exposed to the sample at the same time.
  • the detection capacitor is electrically isolated from the reference capacitor.
  • FIG 4B details a top view of an alternative arrangement where two separate fluidic channels 430, 435 pass through the capacitor (C ref ) of a reference chamber 415 and the capacitor (C detect ) of a detection chamber 420.
  • FIGs. 4C and 4D detail top and cross-sectional views respectively of a similar embodiment to that shown in FIGs. 3 A and 3B but that uses semiconductor or insulator pillars 440 arranged between the chambers to regulate the flow speed of the sample through the channel.
  • the integrated circuit and microfluidic channel manufacturing process is separated from the process of selectively attaching the probes or unreactive probes to the capacitor electrodes of specific detection and reference chambers respectively.
  • This separation provides the ability to customize the apparatus at the level of the individual detection or reference chamber while maintaining the economies of scale associated with 1153.129WO1 9 traditional semiconductor or microfluidic manufacturing methods.
  • it allows for the reuse of the apparatus by refunctionalizing the detection and reference chambers with new probes and unreactive probes respectively. In doing so, the manufacturing cost associated with each detection is reduced.
  • the ability to selectively attach different probes and unreactive probes to the capacitor electrodes of specific detection and reference chambers respectively enables the apparatus to be configured to detect different targets in different detection chambers. This allows for the detection of multiple targets with a single sample. An application of this might enable the apparatus to use a single sample to detect multiple diseases and/or diseases which are diagnosed by the identification of multiple protein components.
  • a first stage involves the immobilization of a linker molecule on the surface of the capacitor electrode of the chamber to be functionalized.
  • the linker molecule is designed such that it has a moiety that can react with the probe (e.g. an amino or carboxyl acid group) and that is initially protected and a ligand which is not protected. The linker molecule will bond via this unprotected ligand to a statically charged electrode surface.
  • the linker molecule is introduced into the fluidic channel while the capacitor of the chamber to be functionalized is charged at the appropriate potential for activating the surface reaction.
  • the linker molecule will thus bind covalently to the capacitor of the addressed chamber.
  • the DC voltage that is applied to the capacitor of the addressed chamber may utilize the same circuitry that is used for applying the detection signal.
  • the second stage involves unprotecting moiety that can react with the probe on the immobilized linker molecule.
  • the third stage involves the introduction of the probe to the channel.
  • the probe will bind to moiety that can react with the probe, which is exposed on the immobilized linker molecule.
  • a fourth step may involve a coating of the probe to prevent denaturing.
  • a proof-of-principle and further embodiments for detecting the difference in dielectric permittivity between two liquid media will now be described, and has been done by simulation using an ADS software package from Agilent Technologies, the worldwide dominant design and simulation software for microwave circuits and components.
  • FIGs. 5A and 5B show the complex permittivity spectra of water and 34.8 mg/mL horseradishperoxidase solution.
  • This data is taken from literature (Yokoyama et al., J.Phys.Chem. B, Vol. 105, No. 50, 2001) and the permittivity numbers used in the simulations are based on this data set. Similar tests may be performed to measure the same kind of data for any protein solution, or in fact any difference in permittivity of any two liquid media. The embodiments may be modified in a manner consistent with the following description for each such difference in permittivity of two liquid media.
  • the permittivity spectra such as that in FIGs. 5A and 5B, form an input to the design and simulation process in ADS. Then, masks may be generated for microfabrication directly from the design in ADS.
  • the comparator 610 splits the incoming signal 615 into two signals of equal power, but in phase, or out of phase, and then at 630, the signals are placed 180 degrees out of phase and combined.
  • the signals are 180 degrees out of phase when combined. Material in the channel of the detection capacitor introduces further phase shift which can be measured.
  • a (parallel) resonance configuration 635 with an inductor 640 tuned approximately to be in resonance with an effective capacitance of a Capacitive Test Cell structure 645 at the operating frequency is provided at the first signal 620.
  • a Capacitive Test Cell (detection chamber) is shown at 650.
  • a physical layout of protein test-chambers is analogous to a microstrip thin-film on-chip capacitor 655, but with the micro fluidic channel and dielectric cladding layers forming the filling between the two "capacitor plates”.
  • An inductor 660 is provided in parallel with the capacitor 655 and both are coupled to signal 625. The electromagnetic behavior in the circuit, is quite different from a simple capacitor.
  • each level is described in more detail, along with how they relate to produce a highly sensitive detector of small changes in permittivity.
  • the comparator 610, 630 is relatively straightforward in its function and design.
  • the equal power split with 180 degree or other phase shift is accomplished in one embodiment with a Rat-Race-Coupler (RR-180), and the equal-power combining at 630 with a Rat-Race-Coupler without or with phase shift (RR-O) used in reverse such that the total phase shift is approximately 180 1153.129WO1 12 degrees.
  • the Rat-Race-Couplers are designed for the target frequency (in the examples herein, 7 GHz) and the substrate properties using ADS. Both elements are passive, and their layout in reality is just a circular metallization pattern of well defined circumference, width and port positions. The designs may be easily modified for other frequencies.
  • the difference between RR-180 at 610 and RR- 0 at 630 lies in which ports are connected.
  • Resonance in various forms is key to converting a small change in permittivity into a large differential signal.
  • the resonance may be important in two ways: one is on the circuit level, which will be discussed in this section, and the other is on the level of the Capacitive Test Cell itself, which will be discussed in the next section.
  • the Capacitive Test Cell being replaced with an ideal capacitor.
  • e' would be about 68 for water and 66 for 34.8mg/ml horseradish peroxidase solution at 7 GHz.
  • Cl (solution) / C2 (water) would therefore be 0.97.
  • the circuit translates a 3% change in relative capacitance to a signal change of 6 orders of magnitude (-104 dB vs. -39 dB).
  • Series resonance improves this only slightly, while the parallel resonance configuration improves the signal by another factor of 30. [0061] The results are quite different between series and parallel resonance.
  • FIGs. 9A, 9B, 9C and 9D examine what is going on in detail for the series resonance case, and FIGs. 1OA, 1OB, 1OC and 1OD examine the parallel resonance. Both sets of figures have the response of the entire circuit as shown in FIG. 8 repeated for reference.
  • FIGs. 9A and 1OA show the measurement setup to produce the graphs in FIGs. 9B - 9D and 1OB - 10D. The complex impedance of each branch is measured separately in an AC configuration, and the corresponding impedance magnitude and phase angle are plotted in the lower halves of the figures respectively.
  • the circuit changes from capacitive to inductive at the resonance frequency with the abrupt 180 degree phase shift at the resonance frequency, and the magnitude of the impedance goes to zero. Due to the slightly different capacitance in the two branches, the resonance frequency shifts, and if one chooses the operating frequency (7GHz) of the circuit to be in between, as indicated in FIGs. 9A- 9D, then one obtains a 180 degree phase shift in one branch, but not the other. Considering just the phase, this scenario would be expected to provide full transmission considering the previous 180 degree phase shift from the Rat-Race- Coupler. But in reality, the improvement due to simple series resonance is minimal as compared to no resonance.
  • any resonant circuit has an associated quality factor, which is a measure of how sharp the resonance peak is as a function of frequency. In the present embodiment, one would expect that the sharper the resonance peak is, the clearer the separation between the two unequal branches and the stronger the output signal.
  • R is the inherent resistance
  • L the inductance
  • C the capacitance and f the frequency.
  • Table 1 shows the results from varying the capacitance in branch A by a factor of 2, while leaving the ratio between the two capacitances fixed.
  • FIG. 11 shows the corresponding output
  • Structure 1200 is designed as microstrip circuits, which means that signal lines are separated from ground via a substrate.
  • Three metal layers, GND 1210, Cond layer 1215 and Cond 2 layer 1220 are shown.
  • Cond layer 1215 is the layer of the passive circuit, and Cond2 layer 1220 is the other plate of the capacitor.
  • GND 1210 is the layer of the passive circuit
  • Cond2 layer 1220 is the other plate of the capacitor.
  • the substrate and thick Si layer may be varied in thickness, and may in fact be any material at all that can be processed. If we can avoid the need for active components, there will be no need for a semiconductor.
  • the "substrate” material can be different from the “carrier” material.
  • SU-8 1255 here is the polymer for
  • the capacitor filling 1230 is formed of a microchannel 1235
  • the channel thickness is indicated as 1 micron, because shallower channels become nominally more difficult to fabricate, but it can certainly be accomplished. From an electrical signal point of few, a thin channel is good since it causes a high capacitance and results in a high volume fraction of the reacted proteins or other substance.
  • boundary conditions there are of course many boundary conditions to be considered: (1) the product of capacitance and inductance determines the resonance frequency, and L cannot be made arbitrarily low nor is it entirely independent nor should the total frequency be too low; (2) fluidynamic considerations; (3) reaction chemical considerations etc.
  • the dielectric cladding layers can be present or absent, and any material can be chosen that can be appropriately deposited.
  • the cladding layers 1245, 1250 fulfill many functions: (1) they provide a surface other than metal for the electrochemical immobilization of the linker molecules, (2) they allow capacitance tuning independent of the channel, (3) they change the intrinsic inductance, (4) they change the intrinsic resistance, (5) they can be crucial for establishing an additional resonance, and probably many other.
  • the depth or thickness of the microchannel varies from significantly thinner than l ⁇ m, such as 0.1 ⁇ m to approximately 10 ⁇ m.
  • the cladding layer also may vary in thickness from approximately 0 to 1 ⁇ m. hi one embodiment, the ratio of thicknesses of microchannel to cladding layer remains approximately 10 to one. In one embodiment, a 0.5 ⁇ m channel is used. Thicker microchannels result in a decrease in effective capacitance.
  • the cladding layers may also be changed in thickness, but a large increase in thickness decreases effective capacitance due to the increased spacing of the capacitor plates and the lower dielectric constant of the cladding material, such as SiO 2 . Thicker cladding may also increase intrinsic inductance at microwave frequencies.
  • the cladding may be used for the cladding as desired, such substantially insulating dielectrics such as oxides, nitrides or similar dielectrics.
  • the material is selected from the group consisting of silicon dioxide, silicon nitride, amorphous polysilicon, crystalline silicon, and polymers. Still further materials with varying dielectric constants may be used.
  • FIG. 13 shows the phase behavior of the impedances of
  • Capacitive Test Cells without cladding layers, a 1 micron channel, a 150 micron x 150 micron square design and a 180 degree contacting geometry.
  • the curves correspond to the pennittivity values indicated on the graph (they are not quite physical at these frequencies, but correspond to the lower frequency limit).
  • FIG. 14 The phase of a signal from the no-absorption structures with an ideal inductor in parallel is shown in FIG. 14.
  • the series self resonance remains, and the ideal inductor creates second resonance (parallel) with the capacitance of the test-structure, the frequency of which can be tuned with the inductor value.
  • These examples illustrate the general behavior of the test-cell structure as a series of resistance-inductance-capacitance. One can determine equivalent values for a specific design at a specific frequency. However, the values can change non-ideally with design parameters, and especially with frequency.
  • a "proof-of-principle" structure at 7 GHz is based on the protein spectra shown in FIG. 5.
  • the structure is considered to be “locally optimized” for 7 GHz, but not necessarily “globally optimized”, and a modified design at another frequency may produce better results. Every design may be optimized in all its parameters depending on the input dielectric spectra.
  • the structure here is the one shown in FIG. 12, which includes the two 0.1 micron silicon dioxide cladding layers 1245, 1250. The inclusion of the cladding layers lowers of course the overall capacitance of the structure, since it increases the plate separation while at the same time introducing material with a 15 times lower permittivity.
  • FIGs. 15 A and 15B illustrate what happens when a 0. InH ideal inductor is placed in series with this structure to tune the resonance frequency down to around 7GHz.
  • the Capacitive Test Cell with water exhibits a near ideal resonance for 145x145 and 150x150 capacitor areas, and slightly less for 140x140, but much less for 155x155 and 160x160.
  • the resonance window is quite narrow and thus sensitive. The solution does not fall into this resonance window for any of the test areas.
  • FIGs. 17A, 17B and 17C show the impedance magnitude of the parallel configuration for all the 5 structures, which vary in their capacitor area exactly as before (FIGs. 15A and 15B).
  • FIG. 17A plots the impedance magnitude for water
  • FIG. 17B that of solution
  • FIG. 17C shows the difference between the two.
  • a similar signature of the additional resonance is observed as discussed with respect to FIGs. 15A and 15B.
  • the impedance is around 50 Ohm, where for water it is above and for solution below this value.
  • a 150x150 micron structure is used as laid out in FIG. 12 and as discussed above with one slight modification in the full microstrip circuit design. Instead of contacting the structure on opposite sides, it is contacted at 90 degrees to better fit the layout in one embodiment. This changes the parameters slightly, but allows design of the circuit from RR-180 to RR-O with metal lines only with the tuning inductor being "created" by the metal trace pattern.
  • FIG. 18 shows the changes in impedance magnitude for the 90 degree contacting geometry of water and solution Capacitive Test Cells. Both peak values are shifted down by about 15 Ohms, and the difference is slightly less.
  • FIG. 19 compares the final result of the fully simulated circuit for
  • Capacitive Test Cell i.e. negative test-case
  • Capacitive Test Cells positive test-case
  • the difference is signal 10 10 at 7 GHz, and at least 10 7 over a frequency range of 0.2 GHz. This frequency stability is helpful, since an input signal has a finite bandwidth.
  • the positive test case returns 4% of the 1153.129WO1 21 input power, which may well be enough for not needing any active components, making it cheaper to manufacture.
  • the power transmitted can be transformed into a higher voltage signal to provide higher output signals if desired.
  • the circuit structures including microstrip circuitry, fluidic channels, and detection and data processing circuitry may be formed in or on a semiconductor substrate. Further circuitry may be included and packaged together on a chip, such as RFID circuitry for transmitting both measured results along with a patient and/or chip identifier. This makes tracking and properly correlating test data to a patient more reliable than current methods, especially given conditions in under-developed areas of the world, where good records may be difficult to create, manage and maintain.
  • the Abstract is provided to comply with 37 C.F.R. ⁇ 1.72(b) to allow the reader to quickly ascertain the nature and gist of the technical disclosure. The Abstract is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.

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  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un dispositif comprenant un séparateur qui sépare un signal variant dans le temps en deux signaux de puissance sensiblement égale. Un condensateur de référence comprenant un canal de fluide formé entre les plaques de condensateur, est couplé à l'un de ces signaux de puissance égale, et un condensateur de détection comprenant un canal de fluide formé entre les plaques de condensateur, et couplé à l'autre signal de puissance égale. Un détecteur est couplé aux sorties du condensateur de référence et du condensateur de détection. Les signaux sont déphasés de 180 degrés l'un par rapport à l'autre lorsqu'aucun analyte n'est présent dans le canal de fluide au niveau du détecteur ou avant ce dernier. Dans une forme de réalisation, ce dispositif est formé d'élément de circuits microrubans ou d'éléments guides d'onde plans, et fonctionne à des fréquences micro-ondes
PCT/US2006/012512 2005-04-05 2006-04-05 Capteur utilisant la permittivite Ceased WO2006107972A2 (fr)

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CN103257268A (zh) * 2013-05-20 2013-08-21 东南大学 一种翘板式智能检测微波功率传感器
WO2014048799A2 (fr) 2012-09-25 2014-04-03 Sony Corporation Dispositif détecteur pour les mesures non invasives de la permittivité diélectrique de liquides

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WO2014048799A2 (fr) 2012-09-25 2014-04-03 Sony Corporation Dispositif détecteur pour les mesures non invasives de la permittivité diélectrique de liquides
WO2014048799A3 (fr) * 2012-09-25 2014-07-31 Sony Corporation Dispositif détecteur pour les mesures non invasives de la permittivité diélectrique de liquides
CN103257268A (zh) * 2013-05-20 2013-08-21 东南大学 一种翘板式智能检测微波功率传感器

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