Analytical device and method utilizing a piezoelectric crystal biosensor
First Claim
1. A device for analyzing biochemicals, microbes and cells in a sample liquid comprising:
- a flow type cell for containing therein a sample liquid;
a piezoelectric crystal sensor incorporated in the flow type cell, the piezoelectric crystal sensor having a piezoelectric crystal and receptor material immobilized or chemically treated on a surface of the piezoelectric crystal, the receptor material being operative to attach thereto a biochemical, microbe or cell specific for the receptor material;
measuring means for measuring the resonant frequency of the piezoelectric crystal to analyze the biochemical, microbe or cell attached to the receptor material; and
replacing means for replacing the sample liquid in the flow type cell by water held at a substantially constant temperature so that the resonant frequency is measured while the piezoelectric crystal is exposed to the water.
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Accused Products
Abstract
A bio-sensor is mounted in a container and comprised of a receptor for selectively reacting with a specific biochemical substance in a sample liquid held in the container to bind thereon the specific biochemical substance and a resonator integrated with the receptor for detecting the amount of the specific biochemical substance bound to the receptor in terms of a resonant frequency shift of the resonator. A measuring circuit is connected to the sensor for measuring the resonant frequency shift of the resonator within the container; a switching valve operates during the reaction of the receptor with the specific biochemical substance to charge a sample liquid into the container to contact the sample liquid with the receptor to thereby effect the reaction and operates during the measurement of the resonant frequency shift to replace the sample liquid by a buffer liquid in the container to immerse the sensor in the buffer liquid to thereby prevent a fluctuation of the resonant frequency shift.
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Citations
52 Claims
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1. A device for analyzing biochemicals, microbes and cells in a sample liquid comprising:
- a flow type cell for containing therein a sample liquid;
a piezoelectric crystal sensor incorporated in the flow type cell, the piezoelectric crystal sensor having a piezoelectric crystal and receptor material immobilized or chemically treated on a surface of the piezoelectric crystal, the receptor material being operative to attach thereto a biochemical, microbe or cell specific for the receptor material;
measuring means for measuring the resonant frequency of the piezoelectric crystal to analyze the biochemical, microbe or cell attached to the receptor material; and
replacing means for replacing the sample liquid in the flow type cell by water held at a substantially constant temperature so that the resonant frequency is measured while the piezoelectric crystal is exposed to the water. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
- a flow type cell for containing therein a sample liquid;
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14. A method for the analysis of biochemicals, microbes and cells contained in a sample liquid using a piezoelectric crystal sensor which has a receptor material, comprising the steps of:
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(a) measuring a resonant frequency F1 of a piezoelectric crystal sensor within water held at a substantially constant temperature; (b) contacting the piezoelectric crystal sensor with a sample liquid contained in a flow type cell and allowing a binding reaction of biochemicals, microbes or cells to be analyzed with a receptor material formed on the piezoelectric crystal sensor; (c) flowing a solution into the flow type cell for removing substances bound to and non-specific for the receptor material from the receptor material; (d) measuring a resonant frequency F2 of the piezoelectric crystal sensor within water held at a substantially constant temperature; and (e) determining a concentration of the biochemicals, microbes or cells specific for the receptor material according to a frequency change Δ
F=F1 -F2 based on a calibration curve obtained previously. - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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26. A method for the analysis of biochemicals, microbes and cells contained in a sample liquid utilizing a piezoelectric crystal sensor which has a receptor material, comprising the steps of:
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(a) contacting the piezoelectric crystal sensor with a sample liquid contained in a flow type cell and allowing a binding reaction of different kinds of biochemicals, microbes or cells to be analyzed with a receptor material formed on the piezoelectric crystal sensor; (b) measuring a resonant frequency of the piezoelectric crystal sensor in another liquid within the flow type cell; (c) flowing an eluent into the flow type cell to selectively remove one kind of biochemicals, microbes or cells bound to the receptor material from the receptor material; (d) measuring a resonant frequency of the piezoelectric crystal sensor in a buffer liquid within the flow type cell; and (e) determining an amount of the one kind of eluted biochemicals, microbes or cells according to the frequency difference of the measured resonant frequencies. - View Dependent Claims (27, 28, 29, 30, 31)
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32. An apparatus for analyzing biochemical substances contained in a sample liquid, comprising:
- a container for holding therein a liquid;
a sensor mounted in the container and comprised of a receptor for selectively reacting with a specific biochemical substance in a sample liquid to bind thereon the specific biochemical substance, and a piezoelectric resonator integrated with the receptor for detecting the amount of the specific biochemical substance bound to the receptor in terms of a resonant frequency shift of the resonator;
measuring means connected to the sensor for measuring the resonant frequency shift of the resonator within the container; and
control means operative during the reaction of the receptor with the specific biochemical substance to charge a sample liquid into the container to contact the sample liquid with the receptor to thereby effect the reaction and operative during the measurement of the resonant frequency shift to replace the sample liquid with another liquid in the container to immerse the sensor in said another liquid to thereby prevent fluctuation of the resonant frequency shift. - View Dependent Claims (33, 34, 35, 36, 37, 38, 39, 40, 41)
- a container for holding therein a liquid;
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42. A method for analyzing biochemical substances contained in a sample liquid by utilizing a sensor comprised of a receptor for selectively reacting with a specific biochemical substance to bind thereon the specific biochemical substance, and a piezoelectric resonator integrated with the receptor for converting the amount of the specific biochemical substance bound to the receptor into a resonant frequency shift thereof, the method comprising the steps of:
- mounting the sensor in a container;
immersing the sensor in a liquid within the container;
measuring an initial resonant frequency of the resonator of the sensor within the container;
contacting the sensor with a sample liquid within the container to selectively bind a specific biochemical substance to a receptor of the sensor;
replacing the sample liquid by another liquid within the container and immersing the sensor in the liquid;
measuring a resultant resonant frequency of the sensor resonator; and
determining the amount of the specific biochemical substance bound to the sensor receptor according to the resonant frequency shift between the initial and resultant resonant frequencies. - View Dependent Claims (43, 44, 45, 46, 47, 48, 49)
- mounting the sensor in a container;
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50. A method for analyzing biochemical substances contained in a sample liquid by utilizing a sensor comprised of a receptor for selectively reacting with a plurality of different biochemical substances specific for the receptor to bind thereon the specific biochemical substances, and a piezoelectric resonator integrated with the receptor for converting the amount of the specific biochemical substances bound to the receptor into a resonant frequency shift thereof, the method comprising the steps of:
- mounting the sensor in a container;
contacting the sensor with a sample liquid within the container to selectively bind a plurality of different specific biochemical substances contained in the sample liquid to the receptor of the sensor;
measuring a first resonant frequency of the sensor resonator within another liquid held in the container;
exposing the sensor to an eluting liquid within the container to selectively elute one of the different biochemical substances bound to the sensor receptor to remove therefrom said one of the different biochemical substances;
measuring a second resonant frequency of the sensor resonator within another liquid held in the container; and
determining the amount of said one of the different biochemical substances selectively eluted from the sensor receptacle according to the resonant frequency shift between the first and second resonant frequencies. - View Dependent Claims (51, 52)
- mounting the sensor in a container;
Specification