Temporally addressable detection array

A detection device and a method of detection are disclosed. The device may have a sensor array, a detector array, and a sensor controller. The sensor array may have a plurality of sensors, each sensor being responsive to a different analyte of interest. Each sensor may also be able to emit electromagnetic energy. For example, one or more of the sensors may include an LED. One or more of the sensors may include a sensing compound within a xerogel, which is responsive to an analyte of interest. In the method, one of the sensors is turned on, and one or more of the detectors are activated to receive electromagnetic energy emitted from the sensor.

FIELD OF THE INVENTION

The present invention relates to devices and methods for detecting analytes in a sample.

BACKGROUND OF THE INVENTION

A standard detection system places a sample in contact with a sensor array platform, and the output from the sensor array platform is detected by a charged coupled device (“CCD”) camera. Unfortunately, CCDs require multiple voltages, they can consume significant electrical power and they require additional post-processing to determine the changes in signals from a given sensor element.

Existing optically-based devices for detecting the presence of analytes, including CCDs, have a configuration whereby all sensor and detector elements are either “on” or “off”. In addition, despite several well-documented advantages, there has not been a marriage of complementary metal oxide semi-conductor (“CMOS”) optical array detectors with discrete or arrayed sensors having a light emitting diode (“LED”) and a xerogel-based sensing compound.

SUMMARY OF THE INVENTION

The present invention includes a detection device having a sensor array, a detector array, and a sensor controller. The sensor array may have a plurality of sensors, each sensor being responsive to a different analyte of interest. Each sensor may also be able to emit electromagnetic energy. For example, one or more of the sensors may include an LED. One or more of the sensors may include a sensing compound within a xerogel, which is responsive to an analyte of interest.

The sensor controller may be in communication with the sensor array. The sensor controller may be able to turn on at least one of the sensors so as to emit electromagnetic energy while another of the sensors is turned off, so as not to emit electromagnetic energy. For example, the sensor controller may turn on one sensor at a time.

The detector array may have a plurality of detectors. One or more of the detectors may be able to receive emitted electromagnetic energy from one or more of the sensors. A receiver may be in communication with the detector array. The receiver may obtain signals from all the detectors when a sensor is turned on, or the receiver may obtain a signal from only one of the detectors when a particular sensor is turned on.

A device according to the invention may include one or more filters. The filter may receive the electromagnetic energy, and some of that energy may be allowed to pass through the filter with relatively little attenuation, compared to other portions of the electromagnetic energy received. One or more of the filters may be tunable, so that the portion of energy passing through the filter with little or no attenuation may be changed. Filters may be provided so that energy from more than one sensor is filtered by a single filter, or so that energy from only one of the sensors reaches a particular filter.

In a method according to the invention, a determination may be made as to whether an analyte of interest is in a sample. In such a method, a device may be provided having a sensor array, a detector array, a sensor controller in communication with the sensor array, and a receiver in communication with the detector array. The sensor array may be contacted with a sample to be analyzed. An input signal from the sensor controller to a first one of the sensors may be provided, which when received by the first sensor, causes the first sensor to emit electromagnetic energy. The electromagnetic energy may be received at the detector array, and a corresponding signal may be provided to the receiver. The signal provided to the receiver may be provided by only one of the detectors, or the signal may be provided by more than one of the detectors. The receiver may then identify the signal as being related to the first sensor. The signal may then be analyzed to determine whether the analyte is in the sample.

FURTHER DESCRIPTION OF EMBODIMENTS OF THE INVENTION

FIG. 1depicts a detection device10according to the invention having a sensor controller13, a sensor array16, a detector array19and a receiver22. The sensor controller13and the sensor array16have an input communication channel25which enables signals from the sensor controller13to reach the sensor array16. The detector array19and the receiver22have an output communication channel28which enables signals from the detector array19to reach the receiver22.

The sensor array16may have more than one sensor31. A sensor31may have an LED34and one or more sensor compounds37.FIG. 2depicts such a sensor31. Each sensor compound37may be chemically sensitive to a different analyte of interest. The LED34and one sensor compound37may be thought of as a single sensor31. However, it should be noted that a single LED34may be used in conjunction with more than one sensor compound37to form multiple sensors31.FIG. 3depicts such a sensor31having a first sensor compound37A and a second sensor compound37B. It may also be possible to form the sensor array16from sensors31that each have one LED34per sensor compound37.

As an example, a single LED34and a single sensor compound37may be used to form a sensor31, and if the sensor array16were composed of 100 such sensors31each having a diameter of 100 micrometers, the sensors31might be formed in a 10×10 array and spaced on 150 micrometer centers. A corresponding detector array19might comprise a 10×10 array of 100 micrometer diameter CMOS detectors spaced on 150 micrometer centers.

The LED34may serve to provide a source of electromagnetic energy to the sensor compound37. In the presence of the analyte of interest and the electromagnetic energy, the sensor compound37may exhibit characteristics that are not present when either the analyte or the electromagnetic energy, or both, are not present. For example, the sensor compound37may fluoresce when the analyte is present and electromagnetic energy is provided to the sensor compound37. There are many such sensor compounds37, and some of them may be purchased from Sigma-Aldrich, Inc. The amount of fluorescence from a given sensor31may be a function of the concentration of the analyte in the sample.

The sensors31in sensor array16may be arranged in a logical order. For example,FIG. 4depicts a sensor array16in which a first set38of sensors31are designed to detect a particular type of analyte, and sensors within that set38may be arranged so that the specificity of the sensors31changes. For example, a first sensor39A in the set38might be responsive to the presence of many different analytes within a class of analytes, the second sensor39B might be responsive to a subset of those analytes, and so on until the last sensor39L in the set38is responsive to only one or two analytes within the class of analytes.

The detector array19may be provided to receive the electromagnetic energy40emitted from the sensor31. The detector array19may have a plurality of detectors43, some or all of which may be CMOS optical detectors. The detector array19may provide an analog output from each detector43to be read out directly by the receiver22.

To determine the presence of a particular analyte, say analyte “X”, an X-responsive sensor “Sx” may be provided, and a corresponding detector “DX” may be provided. In a similar manner, to determine the presence of analyte “Y”, a Y-responsive sensor “SY” may be provided, and a corresponding detector “DY” may be provided. In this fashion, a “one-to-one match” between each sensor31and each detector43may be established. Such a design may require accurate alignment of the sensor array16and detector array19so that electromagnetic energy40from each sensor31may be received by the corresponding detector43.

The relative positions of DXand Sxmay need to be positioned to prevent cross-talk. For example, assuming the analyte of interest is analyte “X”, DXmay be positioned relative to other detectors43so that DXreceives detectably more energy from SXthan the other detectors43. Alternatively, or in addition, SXmay be positioned relative to other sensors so that D, receives more energy from Sxthan the other detectors43. A lens or lenslet array may be used to focus energy40from a particular sensor31to its corresponding detector43, and in this fashion, the detectors43may be placed closer together, the sensors31may be placed closer together, or both.

The energy40emitted from a particular sensor31may not be uni-directional. For example, if each sensor31has a corresponding detector43, each detector43might receive energy from a number of neighboring sensors31. To avoid this, only one sensor31may be activated at a time, and so the signal provided by the detector array19at a particular time will correspond to the presence or absence of the analyte corresponding to that particular sensor31.

Embodiments of the invention may be provided in which a sensor array16has independently addressable sensors31so that only those sensors31that are of interest at a particular time may be turned on. The sensor controller13may be used to turn sensors31on and off at desired times. Further, the detector array19may be comprised of independently addressable detectors43, so that only those detectors43that are of interest at a particular time may be turned on. For example, the sensor controller13may be used to turn detectors43on and off at desired times so that a sensor31and its corresponding detector43are turned on at the same time and turned off at the same time. However, it should be noted that the invention may be implemented via a detector array19comprised of detectors43which are not independently addressable.

Each sensor31may be turned on selectively by applying a voltage at a particular location (see for example, Jiang, H. X., Jin, S. X., Li, J., Shakya, J., and Lin, J. Y., “III-nitride blue microdisplays,” Applied Physics Letters, 2001 78(9) p. 1303-1305; Ozden, I., Diagne, M., Nurmikko, A. V., Han, J., and Takeuchi, T., “A matrix addressable 1024 element blue light emitting InGaN QW diode array,” Physica Status Solidi a-Applied Research, 2001 188(1) p. 139-142). The controlling circuitry for the sensor array16may be on the same integrated circuit (“IC”) as the detector array19, or on a separate controlling IC. Each sensor31may be activated by applying a DC voltage for a particular length of time, ton. Alternatively, the voltage applied to each sensor31may be modulated at some frequency, fmod, which may also allow each sensor31to exhibit its own, unique modulation frequency. Using a DC voltage may allow for amplitude information to be obtained, while modulating the voltage applied to a sensor31may allow for phase measurements.

Having provided a general overview, two example embodiments of the invention will be considered. In the first example, one sensor31is activated at a time, and the responses of all detectors43are combined to obtain one output signal provided to the receiver.FIG. 5depicts the sensor31and detectors43that are active in this first example at a particular instant of time by blackening the location of the active sensor31and active detectors43. In this example, alignment of the sensor array16with the detector array19may be relatively simple, since precise alignment is not necessary. In a second example, one sensor31and its corresponding detector43are activated at a time, and the output signal from the detector43is provided to the receiver22.FIG. 6depicts the sensor31and detector43that are active in this second embodiment at a particular instant of time by blackening the location of the active sensor31and active detector43. This example embodiment of the invention may use less power because only one detector circuit is active at a time, but better alignment than the previously described first example may be needed.

Both examples may use a sensor array16that has addressable sensors31, and both examples may have the sensor compounds37formed directly on LEDs34. Methods of forming the sensor compounds37on the LEDs34may include those disclosed by E. J. Cho, F. V. Bright, “Integrated Chemical Sensor Array Platform Based on a Light Emitting Diode, Xerogel-Derived Sensor Elements, and High-Speed Pin Printing,” Analytica Chimica Acta, vol. 470, pp. 101-110, 2002). In both examples, the LEDs34may be sequentially turned on by the sensor controller13. The timing associated with sequentially turning on the LEDs34may be used by the receiver22to identify portions of the output signal being provided to the receiver22. For example, time-slicing may be used to correlate a portion of the output signal with a particular sensor31.

A filter46may be used to augment the ability of the detector array19to receive energy40that is of interest. A narrow-band optical filter46may be included for this purpose. For example, if a sensor compound37is known to fluoresce at a particular wave length, then it may be beneficial to filter the energy40emanating from that sensor31so as to attenuate other wavelengths. By using a filter46, the ability of a detector43to receive energy emanating from its corresponding sensor31may be improved. By attenuating unwanted wavelengths, the detector43should be more likely to provide an output signal to the receiver22that properly indicates the state of the sensor31. Further, a filter46may reduce or eliminate the chance that a detector43will sense energy40from a sensor31that does not correspond to that detector43. A filter46may be provided to filter energy40from one sensor31, a group of sensors31or all sensors31in the sensor array16. The filter46may be electrically tunable, such as a short cavity Fabry-Perot filter, and in this manner, the filter characteristics may be altered.

FIG. 7shows a first configuration according to the invention in which a single large area electrically tunable filter46is placed between the sensor array16and the detector array19. Unfiltered energy40A is received by the filter46, and filtered energy40B leaves the filter. Adjustments to the filter46may be timed to coincide with the particular sensor31that is turned on. For example, when a first sensor31is turned on, the filter's characteristics may be adjusted to attenuate electromagnetic energy that may interfere with detection of fluorescence by the first sensor's31sensor compound37. Then, when a second sensor31is turned on, the filter's characteristics may be adjusted again to attenuate a different wavelength that may interfere with detection of fluorescence by the second sensor's31sensor compound37.

In a second configuration of a device having a filter, each sensor needing a filter may be provided with an integral filter. The filter may be formed on the sensor between the LED and the sensor compound (seeFIG. 8), or the filter may be formed on the sensor so as to reside between the sensor compound and the detector array (seeFIG. 9). This second configuration may be implemented in a manner which does not require adjusting the filter characteristics to match the particular sensor31that is turned on.

In a third configuration of a device having a filter46, an array of filter elements49A,49B,49C may be placed between the sensor array and the detector array. One implementation of this configuration would be to provide a filter array having a first filter element49A that serves to attenuate electromagnetic energy from a first group of sensors, and a second filter element49B that serves to attenuate electromagnetic energy from a second group of sensors.FIG. 10depicts such an arrangement. This configuration may reduce the number of filters46that are needed, and may reduce or eliminate the number of adjustments to the filter46in order to match the particular sensor31that is turned on.

FIG. 11shows steps of a method according to the invention. Such a method may be used to determine whether an analyte is in a sample. Such a method may begin by providing100(a) a sensor array having a plurality of sensors, each sensor being responsive to a different analyte of interest, and each sensor being able to emit electromagnetic energy, (b) a detector array having a plurality of detectors, each detector being able to receive electromagnetic energy emitted from the sensor array, (c) a sensor controller in communication with the sensor array, and (d) a receiver in communication with the detector array. The sensor array may be contacted103by the sample, and an input signal from the sensor controller may be provided106to a first one of the sensors so as to activate only that sensor. The first one of the sensors may receive109the input signal from the sensor controller and emit112electromagnetic energy. The emitted electromagnetic energy may be received115at the detector array, which then may provide118an output signal, which corresponds to the emitted electromagnetic energy, to the receiver. The receiver may identify121the output signal as being related to the first one of the sensors, and analyze123the output signal to determine whether the analyte is in the sample.

After the first one of the sensors emits electromagnetic energy, the first one of the sensors may be turned off by the sensor controller, and a second one of the sensors may receive an input signal from the sensor controller, so as to activate only the second sensor. The steps identified above as steps112through123may be performed with respect to the second sensor. After the second sensor emits electromagnetic energy, the process may be repeated with other sensors in the sensor array. In this fashion, the sample may be tested for a plurality of analytes using a single device and in a short amount of time.

In an embodiment of the method, the signal provided to the receiver may correspond to more than one of the detectors (seeFIG. 2). Alternatively, the signal provided to the receiver may correspond to only one of the detectors (seeFIG. 3).

Although the present invention has been described with respect to one or more particular embodiments, it will be understood that other embodiments of the present invention may be made without departing from the spirit and scope of the present invention. Hence, the present invention is deemed limited only by the appended claims and the reasonable interpretation thereof.