The invention will be described by reference to the preferred and alternative embodiments thereof in conjunction with the drawings in which:
a is an illustrative graph of the ion transmission factor and the full width at half maximum (FWHM) as a function of drive voltage, VL;
b is an illustrative scan at a low flow rate;
c is an illustrative scan at a high flow rate;
Preferred embodiments of the present invention include a FAIMS system such as the one described in PCT application numbers PCT/GB2005/050124 and PCT/GB2005/050126, referred to collectively as “Owlstone” and herein incorporated by reference in their entirety.
A control module 140 receives the processed signal from the signal processing module 130 and can change one or more operating parameters of the sensor 100 based on the received signal. Control module 140 may include a communication module 135 that receives instructions for the control module 140 and transmits alarms or sensor status information to a central station. In some embodiments, the control module 140 may be incorporated as part of the sensor package. In other embodiments, the control module 140 may be a wireless transmitter/receiver configured to transmit the signal from the signal processing module and receive commands from a remote control module. Removing the control module from the sensor package reduces the cost and power requirements of the sensor 100 enabling the deployment of many such sensors over a wide area.
Filter 115 is preferably a 2/2-electrode filter that generates an asymmetric oscillating electric field and a compensation field that are both transverse to the ion's direction of travel through the filter. The convention used herein to describe the filter uses two numbers that represent the number of electrodes and the number of contact pads per electrode separated by the “/”. A 2/2-electrode filter, therefore, describes a two-electrode configuration with each electrode having two contact pads. The use of more than one contact pad per electrode enables independent control of the transverse and longitudinal fields generated by the 2/2 electrode filter. In a preferred embodiment, the two-electrode filter may also generate a longitudinal drive field that pumps ions through the filter 115. The asymmetric oscillating electric field is generated by applying appropriate voltage signals to each of the four contact pads of the filter. The asymmetric voltage signal is generated by an asymmetric pulse generator 150 and amplified with a high voltage amplifier 155. The pulse width, repetition rate, and amplitude of the asymmetric voltage signal are set by the control module 140 through an electronic input interface 145. The transverse compensation field is generated by applying an appropriate compensation voltage signal to each of the contact pads in the filter. A voltage source 157 generates the compensation voltage signal with the amplitude and sweep rate of the compensation voltage signal controlled by the control module 140 through the electronic input interface 145. A power supply provides the necessary power to each of the components shown in
In
A larger peak produces a larger signal-to-noise ratio, which gives greater confidence that the target analyte has been correctly detected and is not due to a random noise fluctuation. A smaller signal-to-noise ratio, as illustrated in the low flow rate plot can increase the incidences of false positives where the lower peak height is difficult to distinguish from the amplitudes of a noise fluctuation. In many instances, a false positive may have little or minor harmful consequences but in other situations, a false positive may generate an unwanted cost. Therefore, reducing the false positive rate of a sensor is usually preferred. In this instance, a high flow rate may be preferred to reduce the false positive rate.
A high flow rate, however, also tends to broaden the peak, which reduces the selectivity of the sensor. A broader peak decreases the ability of the sensor to distinguish between two different ionic species, in other words, the selectivity of the sensor is reduced. High selectivity is desired to distinguish a target species from other benign species that may be present in environment of the sensor. If a target species is close to a benign environmental species, a scan may show a single broad peak instead of two closely spaced peaks with one peak representing the target species and the second peak representing the benign species. In such a situation, the sensor cannot determine if the detected peak is only the expected benign species or if the broad detected peak includes the target species. If the sensor is configured to raise an alarm when a broad peak is detected, the false positive rate increases. If, on the other hand, the sensor raises an alarm only when two distinct peaks are detected, the sensor may fail to raise an alarm when the target species is actually present. Therefore, increasing the flow rate through the FAIMS sensor increases the signal-to-noise ratio of a detected peak but decreases the selectivity of the FAIMS sensor.
a is an illustrative graph of the ion transmission factor 740 and the full width at half maximum (FWHM) 720 as a function of drive voltage, VL. The drive voltage, VL, is preferably a DC voltage applied across the top 315, 316 and bottom 317, 318 contact pads of the filter that acts to drive, or pump, the ions through the filter. Increasing VL increases the ion flow rate through the filter. The peak height is approximately proportional to the product of the ion transmission factor and drive voltage. In
An operator of the FAIMS sensor may set an operating point of the device by setting an operating parameter such as, for example, the drive voltage to a desired value. If high selectivity is desired, a small drive voltage may be selected. Conversely, if high sensitivity is desired, a large drive voltage may be selected. The antagonistic relation between sensitivity and selectivity on drive voltage, however, prevents the use of drive voltage to set the operating point of the device such that sensitivity and selectivity are both maximized. The ability to change the drive voltage, however, enables the operator of the FAIMS sensor to program a controller to dynamically change the operating point of the device in response to detected changes in the environment.
The sensor operates in the high sensitivity mode until step 920 when a possible event is detected. The occurrence of an event may be detected based on one or more predetermined threshold values. For example, if the ion current at a predetermined compensation voltage corresponding to a target analyte rises above an event threshold value, the control module may classify the occurrence as an event. At step 930, the control module changes the operating parameters of the sensor to increase the selectivity of the sensor by, for example, decreasing the drive voltage. The control module may also adjust other operating parameters such as sample time, peak RF voltage, or the scan range of the compensation voltage to assist in detecting a second event while in the high selectivity operating mode. At 940, the processed signal is compared to a second predetermined threshold value and an event is declared if the processed signal exceeds the second predetermined threshold value. If a second event is not detected in the high selectivity-operating mode, the control module classifies the event as a false positive event, jumps back to step 910, and changes the operating parameters of the sensor to the high sensitivity-operating mode.
If a second event is detected at step 940, a classification confidence statistic is estimated using Bayesian classification algorithms. By changing the operating point of the sensor, the confidence statistic can be increased. For example, the initial high sensitivity mode event may produce a confidence statistic of less than 95% likelihood that the analyte is present. By changing the operating point of the sensor to a high selectivity mode, the confidence statistic may be increased to greater than 95% and preferably greater than 99% likelihood that the analyte is present.
In step 960, the event is compared to one or more predetermined alarm criteria and if the alarm criteria are met, an alarm is set in step 970. If the event does not met the alarm criteria, the control module jumps back to step 930 and repeats the high selectivity measurement. An example of an alarm criterion is greater than 95% likelihood that the analyte is present. The alarm confidence level may be selected by balancing the cost of a false alarm against the cost of not detecting the analyte when it is actually present. For example, if the target analyte is a toxin that could result in death, the confidence level may be set to a lower value such as, for example, 90% to increase the probability that an alarm is initiated if the toxin is present. If, on the other hand, the target analyte is merely a nuisance but the cost of an evacuation is large, the confidence level may be to a higher value such as, for example, 99% to reduce the incidences of false positive events that require an evacuation.
In some embodiments, a second operating parameter may be adjusted to change dynamically the operating point of the sensor. An example of such an operating parameter is the pulse height of the transverse oscillating field.
In some embodiments, both the drive voltage and the pulse height may be adjusted to increase both sensitivity and selectivity of the sensor simultaneously. Increasing the drive voltage increases the ion flow through the sensor and increases the sensitivity of the sensor. Increasing the pulse height increases the ion mobility differences between species and increases the selectivity of the device. Selection of the pulse height depends on the target species and the environmental species that are expected to be present during deployment of the sensor. The pulse height may be selected to maximize the selectivity of the target species from the expected environmental species.
The sensor described in the Owlstone applications are very compact and inexpensive to fabricate compared to the original benchtop-sized FAIMS device. The filter disclosed in the Owlstone applications may be less than 10 cm2 in surface area and are preferably less than 5 cm2 in surface area. The small size of the filter enables the packaging of more than one filter in a housing that is less than about 0.5 L. The use of multiple sensors in a sensor array can increase selectivity and reduce the false positive rate of the device.
Each sensor shown in
If the sensor array does not have access to an external power source and must use a portable power source such as, for example, a battery, the deployed lifetime of the sensor may be extended by turning on each sensor only when required. The battery life is extended because it does not have to continually power each sensor in the array but turns on each sensor only when necessary. For example, a first sensor in the sensor array may have its operating point set to a high sensitivity mode. During deployment, only the first sensor operates until it detects a possible event. When the first sensor detects a possible event by exceeding a first threshold criterion, for example, a second sensor is activated. The second sensor is set to a different operating point from the first sensor, preferably to an operating mode that has a higher selectivity than the first sensor. If a second threshold criterion associated with the second sensor is exceeded, a third sensor operating at a third operating point and having a third threshold criterion is activated. If the second threshold criterion is not exceeded, the event is probably a false signal, the second sensor is deactivated, and the first sensor is reset to continue monitoring its environment. The sequential activation of sensors in a cascading series of, for example, increasing sensitivity continues until all sensors in the array have been activated. An alarm is registered only when each sensor in the array has exceeded its respective threshold criterion.
When a possible event is detected, the controller activates a next sensor in a sensor array at step 1330. The next sensor is set to a predetermined operating point that may depend on the target species and on the operating point of the previous sensor in the sensor array. For example, if the next sensor in the sensor array is the second sensor, the operating point of the second sensor may be set to higher selectivity mode relative to the first sensor's operating point. For example, the pulse height of the asymmetric oscillating field generated in the second sensor's filter may be set to a larger value than the pulse height of the first sensor's oscillating field.
The processed signal from the second sensor is compared to a predetermined threshold value associated with the operating point of the second sensor in step 1340. If the signal does not exceed the threshold value, the possible event may be classified as a false positive and the controller jumps back to step 1310 and may deactivate the second sensor. If the signal exceeds the threshold value, the controller determines if the most recently activated sensor is the last sensor in the sensor array in step 1350. If the most recently activated sensor is not the last sensor in the sensor array, the controller jumps back to step 1330 and activates the next sensor in the sensor array. For example, if the second sensor is the most recently activated sensor in a five-sensor array, the controller activates the third sensor in the sensor array and sets the third sensor's operating point to a predetermined operating point. The operating point of the third sensor may be set such that it has higher selectivity than the first or second sensor.
If the most recently activated sensor is the last sensor in the sensor array, then all the sensors in the sensor array have exceeded their respective thresholds and an alarm is registered in 1360.
The ability to control independently each sensor in the sensor array allows for a wide variety of operating modes that can be customized to a particular situation. For example, instead of operating the sensor array in a cascading sequence, the sensor array may be operated using groups of sensors within the sensor array.
In some embodiments, a sensor in the sensor array may be controlled to operate in a high sensitivity mode while the remaining sensors in the array are turned off to prolong battery life. When the high sensitivity sensor detects a possible event, the remaining sensors in the array may be turned on and set to a high selectivity operating point. Although the sensitivity of each sensor may decrease as selectivity increases, the activation of the remaining sensors in the array increases the effective flow of ions through the sensor array, thereby increasing the sensitivity of the array while operating in a high selectivity mode.
In some embodiments, the remaining sensors in the array may be controlled as a single group of sensors set to the same operating point, thereby making the group of sensors appear to be a single sensor with a large flow, or collection, cross-sectional area. For example, if the sensor array has nine FAIMS sensors with eight of the sensors controlled as a single group, the array will appear as a two-sensor array with the second sensor having an effective area that is eight times as large as a single FAIMS sensor. Operating the group of sensors at the same operating point may eliminate the need for separate electrode drive electronics, thereby reducing the cost and size of the sensor array.
Embodiments of the present invention comprise computer components and computer-implemented steps that will be apparent to those skilled in the art. For ease of exposition, not every step or element of the present invention is described herein as part of a computer system, but those skilled in the art will recognize that each step or element may have a corresponding computer system or software component. Such computer system and/or software components are therefore enabled by describing their corresponding steps or elements (that is, their functionality), and are within the scope of the present invention.
Having thus described at least illustrative embodiments of the invention, various modifications and improvements will readily occur to those skilled in the art and are intended to be within the scope of the invention. Accordingly, the foregoing description is by way of example only and is not intended as limiting. The invention is limited only as defined in the following claims and the equivalents thereto.