Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
2001-06-22
2002-11-19
Siew, Jeffrey (Department: 1637)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C435S006120, C435S007100, C435S091100, C435S091200, C536S022100, C536S023100, C536S024300, C536S024310, C536S024320, C438S049000
Reexamination Certificate
active
06482639
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is a microelectronics-based sensor, specifically, a microelectronics-based transducer for molecular recognition-based sensors for detection or quantification of charged and uncharged target molecules.
2. Description of the Background Art
Molecular recognition-based sensors are important research tools because of the wide range of target molecules for which receptors can be harvested or synthesized. They have proven indispensable in genomic and pharmaceutical research and development configured in high-density arrays of thousands of individual sensor elements, each element being responsive to a specific target molecule by immobilization of a corresponding molecular receptor. Such arrays enable simultaneous detection of thousands of target molecules from mixtures. Currently, the detection of chemical and biochemical species utilizing molecular recognition elements is dependent upon the use of labels or reagents including, but not limited to, fluorophores, radioisotopes, and enzymes that generate a measurable signal to report binding of target molecule by the receptor molecule. The use of such labeling reagents is labor intensive, equipment intensive and is prone to human and equipment error. Further, the difficulty in the use of labeling reagents has prohibited widespread application of molecular receptor recognition-based sensing outside research and development environments. Further, the use of labeling reagents precludes real time diagnostics in the field.
Further, the current methods for the detection of chemical and biochemical species utilizing microelectronics-based transducers (i.e., field effect transistors (FETs)) depend upon a change in FET gate charge as the sensing approach. Many target molecules of interest are uncharged, therefore they are not detectable using the current microelectronics-based transducers.
Therefore, there is a strong need in the field to provide devices and methods capable of sensitive and accurate detection of target molecules without the use of labeling reagents. Further there is a strong need for devices and methods for label-free assays capable of real-time analysis in vitro and in vivo. Further, there is a strong need for arrays for simultaneous detection of multiple target molecules without the use of labeling reagents.
Further, there is a strong need in the art for devices and methods to detect both charged and uncharged target molecules.
OBJECTS OF THE INVENTION
Accordingly, it is an object of the present invention to provide molecular recognition-based electronic devices and methods capable of sensitive and accurate detection of target molecules without the use of labeling reagents.
It is another object of the present invention to provide molecular recognition-based electronic devices and methods of label-free assays capable of real-time analysis in vitro and in vivo.
It is another object of the present invention to provide for arrays for simultaneous detection of multiple target molecules without the use of labeling reagents.
It is another object of the present invention to provide devices and methods to detect both charged and uncharged target molecules.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
SUMMARY OF THE INVENTION
According to the present application, the foregoing and other objects and advantages are attained by providing a sensor comprising a gateless, depletion-mode, field effect transistor (FET) having a source implant and a drain implant that are spatially arranged within a semiconductor structure and separated by an active channel. A dielectric layer covers the active channel between the source and drain, and the dielectric layer surface is modified with immobilized molecular receptors. The receptor-modified dielectric layer surface contacts a sample solution. The immobilized molecular receptors are available to bind target molecules present in the sample solution. The FET-based sensor is imbedded in a substrate with its receptor-modified dielectric layer exposed, and electrical connections are available for applying bias between the source and drain and between a reference electrode in the sample solution and the FET semiconductor substrate. The sensor detects the presence of target molecules in the sample solution by measuring the change in current between the source and drain that occurs due to either the change in capacitance of the receptor-modified dielectric film/sample solution interface when target molecules bind to the molecular receptors, or when charged molecules bind to the receptor-modified dielectric film/sample solution interface.
Another aspect of the invention provides for a sensor array, with at least two sensors as described above. Each sensor is fabricated into a common substrate with each individual sensor's respective receptor-modified dielectric layer exposed. Each sensor is individually modified with molecular receptors. The sensors operate in parallel and are individually electrically addressable.
Another aspect of the invention provides for a method for detecting a target molecule species by contacting the sensor of the present application with a sample solution, which creates an interface between the sample solution and the receptor-modified dielectric layer. The binding of target molecules to the receptor molecules immobilized on the dielectric layer changes the interfacial capacitance that exists between the sample solution and the receptor modified dielectric layer. This change of interfacial capacitance changes the conductivity of the active channel. The conductivity of the active channel modulates an externally supplied current flowing through the active channel when a terminal bias is applied between the source and the drain. The modulation of the externally supplied current flowing through the active channel can be measured to detect binding of the target molecules to the molecular receptors. The methods and devices of the invention remove the dependency of molecular-recognition-based sensors on labeling reagents, which enables a wider scope of practical and worthwhile utilization of recognition-based sensors. The removal of dependency of molecular recognition-based sensors on labeling reagents also makes possible in vivo application of miniaturized sensor arrays for medical research and real time treatment assessment.
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IEDM Technical “An Active Microelectronic Transducer for enabling Label-Free Miniaturized Chemical Sensors” p. 407-410 Dec. 10, 2000.
Provisional Application-60/213,471“Capacitance Coupled Field Effect Transistor” Filed Jun. 23, 2000.
Fertig Stephanie J.
Peckerar Martin
Perkins Frank K.
Snow Eric S.
Tender Leonard M.
Grunkemeyer Joseph T.
Karasek John J.
Siew Jeffrey
The United States of America as represented by the Secretary of
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