The present invention relates to high sensitivity sensor devices and its related signal processing circuits to detect the gas, biomolecules, or biochemical agents. More specifically, this invention is related to sensor device comprising with at least one nano-chip for application in biomedical and industrial applications.
A large benefit of this sensor according to this invention, is that there can be several on a single wafer. It is a device able to measure chemical agent concentrations at the part-per-billion (ppb) level and accurately determine the biomolecule agent and volume of biological cells present in human body. There is no device in the state-of-art, which allows concurrent detection of a chemical agent, biomolecule agent, and biological cell, all in a single system.
There are various kinds of sensor system.
Several techniques can be found as the prior art for detecting concentration of specimen (common term used hereafter separately for chemical, biomolecule agents, or biological cells). However, most of them are based on the standard electrical technique wherein only single specimen is considered to detect. In addition, most technique requires long time in detection and/or not highly sensitive. The following, as a point of reference, are some methods, which are already patented and described as biosensors, used for detection of biological cells.
Peeters, in U.S. Pat. No. 6,325,904, (issued on Dec. 4, 2001), discloses a nanosensor, using an array of electrodes at the atomic or nano scale (nanoelectrodes) level, formed by using specific receptors. Utilizing the level of current flow while specific biological cells attached determine the concentration. The drawbacks of such technique are: (i) requiring STM to position the receptor which time consuming fabricating such sensor, (ii) requiring specific nano-scale level gap in between electrodes containing receptor to conduct current, (iii) difficulties in measuring low current level (corresponding to low concentration) due to use of computer controlled technique, and (iv) requiring high power due to using of computer controlled signal processing.
Bornhop, et al., in U.S. Pat. No. 6,809,828, (issued Oct. 26, 2004), discloses an sensor system for detecting proteins or DNA. Concentration is estimated based on the fringe pattern, detected by the CCD camera in addition with laser beam analyzer. Fringe pattern is usually depending on the laser intensity and position of the CCD camera. The drawback of this technique are, (i) in accuracy in concentration measurement as fringe pattern is dependent on the laser intensity and position, (ii) difficulties in low level concentration measurement due to difficulties in finding small changes in fringe pattern, and (iii) complete system becoming bulky as CCD camera, position sensor, and laser beam analyzer are to be used.
Britton, Jr., et al., in U.S. Pat. No. 6,167,748, (issued Jan. 2, 2001), discloses a technique for detecting the glucose concentration in blood.
Measurement of concentration is performed based on standard technique of measuring the changes in capacitance. Technique uses cantilever coated with the receptor for absorbing the glucose. Main drawbacks are: (i) inability to detect low level concentration as very low changes in the capacitive is difficult to measure, and (ii) difficulties of detection of different kind of biological cell at the same time as each cantilever require different coating. Similar detection techniques can also be found in other patents such as U.S. Pat. No. 6,856,125, of Kermani (issued Feb. 15, 2005), U.S. Pat. No. 5,798,031 Charlton et al., (issued Aug. 25, 1998), U.S. Pat. No. 5,264,103 of Yoshioka et. al., (issued Nov. 23, 1993), and U.S. Pat. No. 5,120,420 of Nankai et. al., (issued Jun. 9, 1992), in all of which capacitive techniques are used to detect the concentration.
Chemical and biological sensors can be miniaturized using nanowires or carbon nanotubes. Continued advances in nanoscience and nanotechnology require tiny sensors and devices to analyze small sample sizes. The following is a discussion of the prior art in sensor fabrication.
After discussing the above issues pertaining to the state-of-art biosensors, chemical sensors, and biomolecule sensors, and methods of making them, we would now like to introduce a novel technique where multiple chemical agents can concurrently be detected in real time and the information can quickly be transmitted to a main station and displayed. It is small in size, so the end user may carry it anywhere to measure the biological cell volume, protein, and biomolecule cells in a medical science application and is also able to do concurrent real time detection of different kinds of chemical agents.
According to this current invention, it is an object to provide a sensor system comprising with a sensor more specifically relates to a novel nano-sensor. It is also object to provide the embodiments including novel methods, systems, devices, and apparatus for sensing one or more characteristics. One aspect of the present invention is a sensor, which is capable of distinguishing between different molecular structures in chemical agents at the same time. It is also capable of distinguishing between different types of biomolecule agents or biological cell concentrations. It is capable of detecting the concentration of different types of chemical agents, biomolecule agents, and biological cells.
This present sensor system is based on any type waveguide, including but not limited to: the slab waveguide, the ridge waveguide, or a dielectric materials structure based waveguide. Its bottom clad (hereafter mentioned as substrate) can be formed using an array of various dielectric materials, structured periodically, which can form the photonic-band-gap (PBG). In waveguide, the guided light usually suffers radiation loss due to weak optical confinement; this happens when the structure is not well optimized or the structural parameters are interrupted. The sensor structure is optimized for a fixed wavelength and is designed in such a way that the propagation loss is minimal. Alternatively, according to this invention, the sensor can also be designed to operate in broadband light operation. In that case, the waveguide for nano-chip can be designed to operate multi-mode of operation.
This sensor detects the concentration of gases (that exist in air) based on the change in the effective refractive index of the substrate caused when biomolecule gas/chemical agents fill the air (or receptor) spaces. The changes in the effective refractive index reduce the output optical power (measurable parameter). By comparing the output optical power with the reference input optical power, the proposed nanosensor can detect the biomolecule gas/chemical agent concentration in ppb levels.
It is noted here that the type of chemical agent/gas can be specified by using a fixed receptor specifically made for absorbing said agent/gas. Also, the type of biomolecule agent or biological cell can be specified by using a fixed receptor to absorb the said biomolecule agent or biological cell. The concentration of the agent/gas and the biomolecule agent, and the volume of biological cells can be ascertained by measuring the output optical power, which is a function of the change in effective refractive index and density. In this case, the detector will detect the presence of a chemical agent/gas or a biomolecule agent or a biological cell. Then it will generate an electrical signal, which will be processed through a processing circuit. After the processing circuit, a digital monitoring system will display the actual concentration present via LED.
The materials used for the nanosensor and surrounding surfaces are selected based on their electrical and chemical properties. The PBG arrays may be included in a chamber, which can retain fluid for biological applications; another set of arrays can be used for chemical agents/gas detection. Several arrays may be used in a single chamber and several different chambers may be used in a single chip. Thus, one system may detect chemical agents/gas, biomolecule agents, and biological cells.
This proposed PBG based nanosensor array and chamber as attached should be separated from each other on a chip, so that each system works properly for each individual application. A Digital Signal Processing (DSP) function, Analog to Digital Converter (ADC), and microprocessor are provided to analyze signals from the nanosensors and/or do real time calculations of the accurate values obtained from the nanosensor.
In some other embodiments a communication setup is used in order to relay the output values long distances. This communication setup is included to analyze the real time sensing values remotely.
Further embodiments, forms, features, objects and advantages of the present invention will be apparent from the following description.
The features and advantages of the present invention will become apparent from the following detailed description of the system, taken in conjunction with the accompanying drawings, wherein
In the following detailed description of the preferred embodiments, reference is made to the accompanying drawings, which form a part hereof, and in which is shown by way of illustration specific preferred embodiments in which the inventions may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention and it is to be understood that other embodiments may be utilized. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined only by the appended claims.
According to this current invention, it is our objective to provide a sensing device comprising with nano-sensor and its signal processing circuit which can have the significantly high sensitivity. The sensor device detects the specimen concentration based on the principle of optics. Using of the nano-sensor and signal processing circuit, according to this invention, high sensitivity can be achieved. Detection is mainly based on detecting the difference in intensity of optical signal obtained after specimen absorb in the receptor and converting to electrical signal and their arithmetic processing to achieve significant high sensitivity.
According to this invention, the processing circuit can be made in hybrid using different functional chips or using single chip having all functions, and those can be fabricated from 350 nm or less geometry. The detector can be chosen based on the wavelength of the light to be used in the system 22. For example, if the wavelength is selected in visible region, the silicon-detector can be used in system 22. On the other hands, if the wavelength of near infrared is chosen, then the detector made from III-V compound semiconductor is required for having higher sensitivity.
According to this invention, the system 22 can be miniaturized into a very small package (e.g. less than 1 to 0.5 inches in dimension). The main advantage of the system 22, according to this invention, is that only the power of output optical signal 18 needs to be known in order to ascertain the concentration. In system 22, very little power will be absorbed by the nano-chip and this is based on the percentage of the refractive index change. The system 22 has two parts: the first is a ‘detection part’ comprising of laser 12, nano-chip 16(a, b, c, d, e), and the detector 20; the second is an ‘analyzing part’, comprising of signal processing circuits 28 and 30.
According to this invention, different nano-chips 16(a, b, c, d, e) are explained in
Receptors 40, shown in
Each rod 32 has a refractive index ‘n’ which can be either equal to ‘ncore’ or refractive index ‘n’ can be greater or less than the core refractive index ncore′. Optical signal input 14 to nano-chip 16a is transmitted through the core 35. Based on the absorption of the specimen (not shown here) by the receptor 40 located in the space between the rods 32, the refractive index of the substrate ‘nsub’ in combination with hollow clad 33 and receptor 40 is changed to ‘neff’, the effective refractive index, and as a result, the power output optical signal 18 is reduced. The concentration of the specimen can be determined by calculating the change of the refractive index of the receptors 40 after and before of absorption of the specimen and the changes in power of the optical signal 18 with respect to input optical signal 14. Changes in power of optical signals between 14 and 18 can be determined by the power-factor, which is defined as the ratio of the output optical power over the input optical power. According to this invention, the main advantage is that by knowing the power factor, the changes in refractive index and also the concentration of the specimen can be determined. By calculating the power-factor, this proposed sensor would give the real-time concentration of the specimen.
Nano-chip 16a used for system 22 is based on photonic-crystal and they are having different structures. Two-dimensional (2-D) or three-dimensional (3-D) photonic crystal can be used to fabricate the nano-chip 16a. In
The nano-chip 16(a, b, c, d, and e), can be fabricated using dielectrics, semiconductor, or polymer materials. The dielectric material can cover all kind of materials having dielectric or optical properties (e.g. refractive index), such as glass, quartz, polymer etc. According to this invention, alternatively, the nano-chip can also be fabricated from semiconductor materials, such as Si, GaAs, InP, GaN, SiC, diamond, graphite etc. which can be fabricated using standard's IC fabrication technology. This nano-chip itself can be from rigid or flexible substrate.
The nano-chip can be fabricated by standard dry or wet etching to form the holes or rods embedded inside the solid or hollow substrate. Alternatively, this can also be fabricated using spin-coated polymer or preformed polymer. The low shrinkage in polymerization and the transparency of the synthesized polyurethane can also be used in fabrication of infiltrated inverse opal elastomeric photonic-crystal structures for the nano-chip according to this invention. The nano-chip 16 (a, b, c, d, and e) can have high-symmetry cross-sections and can allow integrated optical networks to be formed by only placing either the rods in air or air cylinders in the dielectric. The nano-chip 16 can also be fabricated in multiple layers by stacking the slabs on top of one another, separating them with a separator. According to this invention, the nano-chip 16(a, b, c, d, and e) and surrounding circuitry can be made into the single chips using today's IC process technology.
The specific specimen can be detected using the nanochip with specific receptor. For example, Avidin Biotin which is the most common uses as a receptor for glycoconjugate analysis and DNA detection systems, can be used also as the receptor 40 in the nanochip 16(a,b,c,d, and e). Single receptor agent or solution linked with other molecule acting as the receptor (for the specific specimen) can also be used as receptor 40. For example, Dimethylsulfoxide (DMSO) solution containing 4 mg/ml of the heterobifunctional linker molecule succinimidyl-6-hexanoate (biotinamido) for a 1 hour at room temperature and the resultant receptor can be used as receptor 40 for DNA detection. According to this invention, the receptor 40 can be gel-type, solid, or solution based.
A derivation is given here for the generalized analytical equation for the nanochip described earlier in
According to this invention, the waveguide structure is to be designed in such a way that maximum optical power for optical signal 18 is achieved (or very to optical power of input optical signal 14), and that condition (or optical power) can be considered as the reference (i.e. with specimen present) in the holes. The symbol used in derivation is summarized in Table I.
For linear system with ridge waveguide, Power Factor, ratio of output optical power (Pout) to input optical power can be derived as follows:
Where, ncref is the reference refractive index of the core with optimized waveguide. nceff is the effective refractive index of the core and nclad is the refractive index of the clad. From Eq. (1a), coupling loss can be written as
Coupling Loss=1−Power Factor (1b)
Where, Coupling Loss is,
From Eq. (1a), relationship between Power Factor and density of the gas can be derived. The relationship between ncref, reference core refractive index (with no gas condition) and ρref, reference density of receptor can be expressed by using of Gladstone-Dale relationship,
n
ref−1=ρref×N (2)
where, N is the Gladstone-Dale constant
As mentioned earlier, after sensing the gas, the density of the receptor ρnew, after absorbing the gas which changes the effective refractive index of the substrate, nceff (mentioned as new core effective refractive index). Similarly, nceff relates with ρnew as,
n
ceff−1=ρnew×N (3)
From Eqs. (2) and (3), this following expression can be derived:
From Eq. (4) nceff expression can be derived as:
After substituting Eq. (4a) into Eq. (1a), we get the new density as follows:
Changes in density ρ can be expressed as,
Δρ=ρnew−ρref (6)
Concentration of the specific gas (considered here only for the biomolecule or industrial gas) in ppm, which is a function of the molecular weight and Δρ, and ppm can be written as
After substituting Eq. (6) into Eq. (7), the concentration of gas in ppm can be expressed as:
Now substitute value of ρnew in Eq. (8) and we can derive ppm, which is
According to this invention, by knowing the power factor (which is ratio of power of optical out 18 to power of optical in 12 to and from the nanochip 16, respectively to the optical input), and appropriate arithmetic signal processing, the concentration of the specimen can be known. According to this invention, the gas is considered, it can be also be used for biomolecule gas, or biomolecule cells, if corresponding receptor is used. From
Photodiodes can be used in either zero bias or reverse bias. In zero bias, light falling on the diode causes a voltage to develop across the device, which leads to current flowing in the forward bias direction. Diodes usually have extremely high resistance when reverse biased. This resistance is reduced when light of an appropriate wavelength incident onto the junction. Hence, a reverse biased diode can be used to generate the photo current. Circuit with reverse-biased detector is more sensitive to light than one with zero-biased detector.
The detector can be p-n junction based detector or avalanche photodiode (APD) detector, According to this invention; both type photodetector (p-n or APD) can be used. Only difference is there operational voltage. For example, APD requires high voltage and on the other hands, p-n junction requires low voltage. By using of APD, according to this invention, single photon level difference in optical power between input to nano-chip and output from nano-chip can be detected.
According to this invention, the signal 26 input to TIA 72 of the integrated circuit 66 to have the proportional voltage output Vin. Initially, the switch S177 is on and switch S278 is off. While the Switch S177 is on, the proportional voltage output Vin is directly feed through the analog memory 74 to store the initial voltage as the reference voltage 76 (output of analog memory 74). Noted here that the reference voltage Vref can be either same or greater than that the proportional voltage output Vin. The reference voltage Vref is integrated by the integrator 73(a) and its output is directly feed to the comparator 73(b) whose other input is set to Vref. While the integrator 73(a) output is reached to Vref, the comparator 73(b) output will reset the integrator 73(a). The resultant waveform 63 from comparator 73(b) is saw-tooth type waveforms as shown in
The signals 29(a) and 29(b) from the processing circuit unit 28 feed to the divider circuit 94 to calculate (1-power factor), as shown in EQ. 9, and its resultant output signal 95 feeds to the n-bit digital signal-processing unit 96, where n is the number of the bit. Other inputs to DSP unit are known parameters such as reference concentration (mentioned as background concentration of the specimen, if any), other required refractive indices related to the nano-chips, explained earlier. The DSP unit 96 is commercially available from various vendors or the unit can be fabricated with standard CMOS technology, depending on the specification criterion. This DSP unit 96 includes a system controller for coordination. The system controller of the DSP unit 96 may be chosen to be an n-bit RISC/CISC-type processor, which is commercially available by various vendors such as Texas Instrument, INtel. The processor and system controller may share a memory for program and data storage.
Output signals of the DSP block 96, which are digital signals, can be converted into analog by using the “DAC” block 100. Output signals from the “DAC” block 100 can be transmitted through the “RF Transceiver” block 102. Signals from block 102 may be wirelessly monitored from the remote “Station” block 106 by using standard wireless protocol such as BLUETOOTH, 802.11a/b/g protocol or other proprietary protocols. The system can be embed with the standard (display) based monitoring unit 104 by feeding a part of DSP signal to the monitoring unit 104 to monitor in real time the concentration of the specimen.
According to this invention, whole processing unit can be made into a single chip and can be fabricated using standard IC technology. Alternatively, whole processing unit can be also build hybridly.
According to this invention,
According to this current invention, any microprocessor, FPGA, or ASIC circuit can be used instead of DSP to perform the DSP functionality. These are available from the commercial vendors. For example, microprocessor can be obtained from Intel, FPGA from Actel and Xilinx, and ASIC circuit could be custom designed for required functionality, and it can be off-shore design and manufacturing.
According to this invention, alternatively the read-out memory circuit can be made based on capacitive load.
According to this invention, the signal processing unit and the monitoring units both as shown in
The splitter can be designed based on the photonics crystals having rod or holes, arranged periodically to made photonic band gap structure. Both splitter and nano-chips can have the same photonic band gap structure or different, and they can be fabricated on the common substrate 136. Alternatively, the splitter can be designed based on the homogeneous (solid) substrate (without photonics crystal) and the nano-chip can be based on photonic crystal base. Again, they can be fabricated onto the common substrate 136, or both splitter 126 and nanochip 16(a, b, c, d and e) can be fabricated in separate substrates, and afterwards hybridly packaged onto the common substrate (not shown here). To detect different types of specimens. For example different bio-molecules, different types of receptors can be used in the nanochips. The outputs from each nanochip are made to incident to the detector 20 to convert optical signal into corresponding electrical signals (not shown here). The electrical signal is processed by the IC 130 to determine the concentration of each specimen. The electrical IC 130 can be single chip or multiple chip based on the circuit means, as explained previously from
According to this invention, specimen 154(a) is made to pass through the inlet 156(a) of the specimen handler 140 and pass out the specimen 154(b) from the outlet 156(b). The passive section of the sensor system 138 is designed in a way that a portion of its internal section is made to expose to the nanochip 16 to make enough contact of the specimen while passing through this specimen handler 140. The optical signal 14 is made to propagate through the nanochip 16 via waveguides 142(a) and 142(b) used for guiding the signals on the passive section of nano-chip 16. For simplicity in handling and also for the purpose of reusage of the sensor system for long time, the passive section can be a separate section apart from the active section, and can be replaceable and easily stackable to the active section. Alternatively, both passive and active sections could be single section attached permanently. In
According to this invention, the active section of the sensor system 138 has signal transmitting section, OE (optical to electrical conversion), and signal processing units (not shown separately). Transmitting section comprises with the laser 12 and driver 122, OE unit comprises with detector 20 and preamplifier 148, and signal processing unit comprising with a chip 150 for further signal processing and monitoring. The signal processing chip 150 contains pre-processing unit, post processing, and monitoring units, explained earlier in
According to this invention, the nano-chip described from
Alternatively, according to this invention, the nanometer sized rods, wire or tubes can also be made from the carbon type materials (semiconductor, insulators, or metal like performances) such as carbon nano-tubes, which could be single, or multiple layered. They can be made using standard growth process for example, MOCVD, MBE, or standard epitaxial growth. According to this invention, the self-assembled process can also be used to make wires, rods, or tubes and their related pn-junction to increase the junction area. These tubes can be grown on the semiconductors (under same group or others), polymers, or insulator. Alternatively, according to this invention, these rods, wire, or tubes, can be transferred to the foreign substrate or to the layer of foreign substrate acting as a common substrate for waveguide for nano-chip. The foreign substrate or the layer of material can be any semiconductor such as Si, Ge, InP, GaAs, GaN, ZnS, CdTe, CdS, ZnCdTe, HgCdTe, etc. The substrate can cover also all kinds of polymers or ceramics such as AlN, Silicon-oxide etc. The material can be conductive or non-conductive.
According to this invention, different substrates can be used for making sensing device as shown in
According to this invention, concentration measurement by determining the power factor is explained here. This nanochip based on photonics crystal can also detect the concentration by other methods, such as measuring the fringe-pattern by using of CCD camera and laser beam analyzer, or absorption spectrum of the optical output by spectroscopy. The concentration and type of the specimen can be known by comparing with the reference pattern for the case fringe pattern technique, and by comparing intensity and chemical absorption for the case of absorption spectrum technique.
Whereas many alterations and modifications of the present invention will no doubt become apparent to a person of ordinary skill in the art after having read the foregoing description, it is to be understood that the particular embodiments shown and described by way of illustration are in no way intended to be considered limiting. Therefore, reference to the details of the preferred embodiments is not intended to limit their scope. Although the invention has been described with respect to specific embodiment for complete and clear disclosure, the appended claims are not to be thus limited but are to be construed as embodying all modification and alternative constructions that may be occurred to one skilled in the art which fairly fall within the basic teaching here is set forth.
Although the invention has been described with respect to specific embodiment for complete and clear disclosure, the appended claims are not to be thus limited but are to be construed as embodying all modification and alternative constructions that may be occurred to one skilled in the art which fairly fall within the basic teaching here is set forth.
The present invention is expected to be found practically use in the industrial, commercial, and bio-medical application. Using of such sensor device will help to detect very low level concentration (in ppb level) of gases, requiring in industrial application. Example of various gases detection using proposed invention can be found in (Sengupta, Rabi and Dutta, A., ‘Novel nanosensor for biomedical and industrial applications’, SPIE Proceed. 6008, Paper No. 60080T, November, 2005). This sensor devices is not limited to use in chemical gas, bio-molecule gas only, this can also be used in biological cell detection and their low level concentration measurement. The main advantages of this invention are that detection and concentration of multiple specimens at a real time can be possible. Multiple specimens can be multiple gases, multiple bio-molecules, or multiple bio-logical cells, or their combinations.
“This is a divisional of application(s) Ser. No. 11/552,080 filed on Oct. 23, 2006”
Number | Date | Country | |
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Parent | 11552080 | Oct 2006 | US |
Child | 13041433 | US |