Abstract: Electrochemical sensors have great promise for point-of-care and in vivo measurement of medically relevant molecules. However, the need for calibrating individual sensors limits the practical applicability of these sensing platforms. The invention provides a novel method of operating electrochemical sensors which obviates the need to calibrate individual sensors against a sample of known concentration. The invention exploits the frequency dependence of electrochemical output signals and the dependence of output signals on the inherent electron transfer kinetics of a selected sensor design. By use of signals generated at a nonresponsive frequency, a normalizing output value is generated that accounts for sensor-to-sensor variation and which enables an accurate calculation of target concentration. The scope of the invention also includes pre-calibrated sensors that may be utilized without calibration steps.

Abstract: Improved electrochemical sensors wherein the recognition element is co-deposited with a secondary, charge transfer modulating moiety, for example an oligonucleotide. The secondary moiety modulates electron transfer kinetics to enhance the frequency dependence of sensor gain, enabling the use of kinetic differential drift correction techniques and like measurements that require a target insensitive signal drifts in parallel with target-dependent output. The secondary moiety also increases the gain and signal to noise of the sensor and can be used to enable calibration-free measurement. Accurate drift-corrected in vivo sensor use with multiple measurements of analyte concentration per minute in flowing blood is demonstrated.

Abstract: The invention encompasses novel methods of operating electrochemical sensors such as aptamer-based sensors to analyze complex samples, such as flowing whole blood both in vitro or in vivo. In such environments, electrochemical sensors are often subject to drift, which complicates the interpretation of sensor output in terms of target concentration. The method of the invention utilizes a dual-reporter recognition element that generates a first, sensing current that is responsive to target binding and to environmental factors and a second, reference current that is only affected by environmental factors. The reference current provides information about environmentally-induced drift, which allows the drift effect to be subtracted out. By removing drift artifacts, electrochemical sensors may be deployed to analyze complex samples, such as whole blood, in vivo.

Abstract: Typical electrochemical sensors measure target-induced changes in current output. Such measures of target binding are inconsistent across individual sensors, and furthermore, signal will drift over time when the sensor is deployed for long periods. These shortcomings can be avoided by the novel use of chronoamperometry to measure current decay kinetics as the indicator of target binding. Current decay lifetimes will vary in a concentration dependent manner, but remain stable across individual sensors and over time, allowing for calibration-free operation. By these methods, aptamer based electrochemical sensors and other sensor types may be deployed in vivo for extended periods of time and will provide accurate measurement of target binding without calibration.

Abstract: Electrochemical sensors have great promise for point-of-care and in vivo measurement of medically relevant molecules. However, the need for calibrating individual sensors limits the practical applicability of these sensing platforms. The invention provides a novel method of operating electrochemical sensors which obviates the need to calibrate individual sensors against a sample of known concentration. The invention exploits the frequency dependence of electrochemical output signals and the dependence of output signals on the inherent electron transfer kinetics of a selected sensor design. By use of signals generated at a nonresponsive frequency, a normalizing output value is generated that accounts for sensor-to-sensor variation and which enables an accurate calculation of target concentration. The scope of the invention also includes pre-calibrated sensors that may be utilized without calibration steps.

Abstract: Embodiments of the disclosed invention provide devices for measuring concentrations of bound and unbound fractions of a target analyte in a biofluid sample. Analytes present in biofluid may be found in a free state, or bound to a binding solute, presenting difficulties for wearable analyte sensors to measure physiologically significant concentrations of the analyte in biofluid. The disclosed devices feature sensors configured to measure both the bound and unbound fractions of the analyte, as well as analyte releasers that cause a portion of the bound fraction of analytes to be released to facilitate measurement. Some embodiments include a collector and or a sample conduit. Other embodiments include a plurality of fluid pathways.

Abstract: The invention encompasses novel methods of operating electrochemical sensors such as aptamer-based sensors to analyze complex samples, such as flowing whole blood both in vitro or in vivo. In such environments, electrochemical sensors are often subject to drift, which complicates the interpretation of sensor output in terms of target concentration. The method of the invention utilizes a dual-reporter recognition element that generates a first, sensing current that is responsive to target binding and to environmental factors and a second, reference current that is only affected by environmental factors. The reference current provides information about environmentally-induced drift, which allows the drift effect to be subtracted out. By removing drift artifacts, electrochemical sensors may be deployed to analyze complex samples, such as whole blood, in vivo.

Abstract: The invention encompasses novel sensor designs that can operate in complex samples like whole blood. The use of protective filtering membranes prevents fouling and erroneous signal drift in sensors such as aptamer based electrochemical sensors. In one aspect, the invention encompasses implantable sensors that can be deployed to the circulatory system of an animal where they can accurately and continuously measure the concentration of a target species, such as a drug, with very short resolution times, for extended periods without signal drift. These sensor designs and associated methods provide a means of accurately dosing animals based on real-time monitoring of drugs and other chemical markers and biomarkers.

Abstract: Embodiments of the disclosed invention provide devices and methods for buffering fluid samples to enable accurate concentration measurements of analytes by salinity-sensitive or pH-sensitive sensors. The buffering capabilities of the device include the ability to control the salinity and pH of a fluid sample, specifically, through the management of solutes such as salts, H+, other ions, and other solutes, that are found in sweat, biofluids, or other fluids. The purpose of such control is to enhance particular fluid sensing device applications by improving detectability of the targeted analyte, or improving performance of analyte sensors. Some embodiments also include components to enable sample concentration to enhance the measurement of low-concentration solutes found in the fluid.

Abstract: A sensor including a flexible substrate, a conductor disposed on the flexible substrate, and a hydrophilic surface coating disposed on the conductor. The flexible substrate and the conductor form wrinkle as a result of the substrate being shrunk. The hydrophilic surface coating is disposed in, e.g., fills, the wrinkles or covers surface areas of the conductor within invaginations of the wrinkles. Also disclosed are methods of preparing the sensor and methods of detecting an amount of an analyte in an aqueous solution. Methods of detecting an amount of analyte can include contacting the sensor with an aqueous solution, and detecting an electrical signal with the sensor, wherein the electrical signal is indicative of the amount of the analyte.

Abstract: A reagentless, reusable bioelectronic DNA, or other oligonucleotide sequence sensor is disclosed. The sensor includes an oligonucleotide (aptamer) probe tagged with a electroactive, redoxable moiety, self-assembled on or near an electrode. This surface-confined oligonucleotide (aptamer) probe structure undergoes hybridization-induced conformational change in the presence of the target which changes the electron-transfer distance between the redoxable moiety and the electrode thereby providing a detectable signal change. In an alternative embodiment, the target can harbor the redoxable moiety.

Abstract: The invention provides a general “signal-on” architecture for oligonucleotide-based detectors that leads to order of magnitude increases in signal gain and sensitivity as compared to prior art detectors. The detectors of the invention rely on base pairing between two oligonucleotide strands, the sensor strand and the blocker strand. In the ‘off’ position of the detector, i.e., in the absence of target, the blocker strand and sensor strand are base-paired. As shown in FIG. 1, the formation of comparatively rigid, duplex DNA prevents the redox moiety from approaching the electrode surface, thereby suppressing Faradaic currents. When target is added to the system, the target displaces the blocker strand, binds to the sensor strand, liberating the end of the redox-labeled oligonucleotide to produce a flexible element. This, in turn, allows the redox moiety to collide with the electrode surface, producing a readily detectable Faradaic current.

Abstract: The invention provides a general “signal-on” architecture for oligonucleotide-based detectors that leads to order of magnitude increases in signal gain and sensitivity as compared to prior art detectors. The detectors of the invention rely on base pairing between two oligonucleotide strands, the sensor strand and the blocker strand. In the ‘off’ position of the detector, i.e., in the absence of target, the blocker strand and sensor strand are base-paired. As shown in FIG. 1, the formation of comparatively rigid, duplex DNA prevents the redox moiety from approaching the electrode surface, thereby suppressing Faradaic currents. When target is added to the system, the target displaces the blocker strand, binds to the sensor strand, liberating the end of the redox-labeled oligonucleotide to produce a flexible element. This, in turn, allows the redox moiety to collide with the electrode surface, producing a readily detectable Faradaic current.

Abstract: A reagentless, reusable bioelectronic DNA, or other oligonucleotide sequence sensor is disclosed. The sensor includes an oligonucleotide (aptamer) probe tagged with a electroactive, redoxable moiety, self-assembled on or near an electrode. This surface-confined oligonucleotide (aptamer) probe structure undergoes hybridization-induced conformational change in the presence of the target which changes the electron-transfer distance between the redoxable moiety and the electrode thereby providing a detectable signal change. In an alternative embodiment, the target can harbor the redoxable moiety.

Abstract: A method, label, and labeling system for labeling and authenticating an item are presented. At least one of a number of known nucleotide sequences associated with a predetermined amount of information is used as a label to be associated with an item. The label is then read with a reagentless sensor to detect the nucleotide sequence(s). The detected nucleotide sequence(s) is then associated with the appropriate information. The item is authenticated if the sensor detects the expected nucleotide sequence(s). The information in the DNA label may also be passed through a hash function or encrypted to further enhance security. The labels may also incorporate known non-natural nucleic acid analog sequences rather than nucleotide sequences, and a reader that reads known non-natural nucleic acid analog sequences may be employed.

Abstract: A reagentless, reusable bioelectronic DNA, or other oligonucleotide sequence sensor is disclosed. The sensor includes an oligonucleotide probe tagged with a electroactive, redoxable moiety, self-assembled on or near an electrode. This surface-confined oligonucleotide probe structure undergoes hybridization-induced conformational change in the presence of the target oligonculeotide sequence which change the electron-transfer distance between the redoxable moiety and the electrode thereby providing a detectable signal change. In an alternative embodiment, the target can harbor the redoxable moiety. In a preferred application, the target sequence is associated with an object and its detection is correlated with the authenticity of the object.

Abstract: A reagentless, reusable bioelectronic DNA or RNA sequence sensor is disclosed. The sensor includes a DNA probe tagged with a electroactive, redoxable moiety, self-assembled on or near an electrode. This surface-confined DNA probe structure undergoes hybridization-induced conformational change in the presence of the target DNA/RNA sequence which change the electron-transfer distance between the redoxable moiety and the electrode thereby providing a detectable signal change. In a preferred application, the target sequence is associated with an object and its detection is correlated with the authenticity of the object.