Sensor strip with multiple sensors for sensing different agents simultaneously

Abstract

Various examples are provided related to simultaneous sensing of different agents. In one example, a medical sensing system includes a portable sensing and readout device including a test strip port that can engage with a disposable multi-channel test strip; pulse generation circuitry that can generate synchronized gate and drain pulses; and switching circuitry that can control application of the synchronized gate and drain pulses to individual channels of the multi-channel test strip for measurement. Each channel can include a functionalized sensing area that can detect an agent different than the other channels. The switching circuitry can electrically couple a first electrode of a channel being measured to a gate pulse output of the pulse generation circuitry.

Description

SENSOR STRIP WITH MULTIPLE SENSORS FOR SENSING DIFFERENT AGENTS SIMULTANEOUSLYCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to, and the benefit of, U.S. provisional application entitled “Sensor Strip with Multiple Sensors for Sensing Different Agents Simultaneously” having serial no. 63 / 632,184, filed April 10, 2024, which is hereby incorporated by reference in its entirety.BACKGROUND

[0002] Breast cancer is the most popular cancer in women. Each year, in the United States, roughly 240,000 women and 2,100 men confront the diagnosis of breast cancer, resulting in approximately 42,000 women and 500 men succumbing to the disease. Noteworthy is that 24% of these cases involve individuals from Black, Indigenous, or People of Color communities. In 2023, an estimated 300,590 new cases and 43,700 deaths were recorded, reflecting an annual increase of 0.5%.SUMMARY

[0001] Aspects of the present disclosure are related to simultaneous sensing of different agents. In one aspect, among others, a medical sensing system comprises a portable sensing and readout device comprising: a test strip port configured to detachably engage with a disposable multi-channel test strip, each channel of the multi-channel test strip comprising a functionalized sensing area configured to detect an agent different than other channels of the multi-channel test strip; pulse generation circuitry configured to generate synchronized gate and drain pulses; and switching circuitry configured to control application of the synchronized gate and drain pulses to individual channels of the multichannel test strip for measurement, where the switching circuitry electrically couples a first electrode of an individual channel being measured to a gate pulse output of the pulsegeneration circuitry. In one or more aspects, the multi-channel test strip can include a plurality of channels. The multi-channel test strip can be a three-channel test strip. The multichannel test strip can comprise a first set of channels on a first side and a second set of channels on a second side. The multi-channel test strip can comprise two channels functionalized with different antibodies for detection of biomarkers. A first channel of the multi-channel test strip can be functionalized to detect HER2 and a second channel of the multi-channel test strip can be functionalized to detect CA 15-3.

[0002] In various aspects, the functionalized sensing area of each channel can comprise two electrodes separated from each other, wherein at least one electrode is functionalized to detect the agent. The switching circuitry can electrically couple one or more individual channel not being measured to ground. The pulse generation circuitry can be configured to adjust the gate pulse. The pulse generation circuitry can comprise a level shifter to adjust voltage of the gate pulse. In some aspects, the pulse generation circuitry can be configured to adjust the gate period. The portable sensing and readout device can comprise an adjustable gain amplifier to measure an output. The adjustable gain amplifier can be a closed-loop programmable gain amplifier. The multi-channel test strip can comprise a combination of pins providing an identification sequence corresponding to the multichannel test strip. The test strip port can be configured to engage with the combination of pins and the portable sensing and readout device can be configured to identify measurement parameters associated with the multi-channel test strip based upon the combination of pins. The medical sensing system can comprise LED indicators configured to provide visual indications of measurement results.

[0003] Other systems, methods, features, and advantages of the present disclosure will be or become apparent to one with skill in the art upon examination of the following drawings and detailed description. It is intended that all such additional systems, methods, features, and advantages be included within this description, be within the scope of the present disclosure, and be protected by the accompanying claims. In addition, all optional and preferred features and modifications of the described embodiments are usable in all aspectsof the disclosure taught herein. Furthermore, the individual features of the dependent claims, as well as all optional and preferred features and modifications of the described embodiments are combinable and interchangeable with one another.BRIEF DESCRIPTION OF THE DRAWINGS

[0004] Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present disclosure. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.

[0005] FIG. 1 is an image illustrating examples of repurposed glucose strips, in accordance with various embodiments of the present disclosure.

[0006] FIG. 2 illustrates an example of the strip functionalization, in accordance with various embodiments of the present disclosure.

[0007] FIGS. 3A-3C illustrate examples of calibration curves for plain saliva and doped saliva, in accordance with various embodiments of the present disclosure.

[0008] FIGS. 4A-4C illustrate examples of digital output readings of human saliva samples and corresponding protein concentrations, in accordance with various embodiments of the present disclosure.

[0009] FIG. 5 is an image of a fabricated printed circuit board (PCB) with a microcontroller to produce the digital sensor output, in accordance with various embodiments of the present disclosure.

[0010] FIG. 6 includes images of a two-channel test strip and graphical representations of the underlying electrode and connecting traces for the 2-channel test strip and a 3- channel test strip, in accordance with various embodiments of the present disclosure.

[0011] FIGS. 7A and 7B illustrate examples of digital readings from the functionalized two-channel strip, in accordance with various embodiments of the present disclosure.

[0012] FIG. 8 is an image illustrating the layout of a PCB designed to facilitate conversion of voltage signals obtained from test strips into digital readings, in accordance with various embodiments of the present disclosure.

[0013] FIGS. 9A-9D illustrate examples of calibration curves of the HER2 and CA 15-3 and output digital reading results with functionalized test strips, in accordance with various embodiments of the present disclosure.

[0014] FIGS. 10A-10D illustrate examples of a low-power handheld pulse waveform detection system and multi-channel test strip configuration, in accordance with various embodiments of the present disclosure.DETAILED DESCRIPTION

[0015] Disclosed herein are various examples related to simultaneous sensing of different agents. Reference will now be made in detail to the description of the embodiments as illustrated in the drawings, wherein like reference numbers indicate like parts throughout the several views.

[0016] Several detection methods have been developed, encompassing biopsy-based, biosensor-based, biomarker-based, screening-based, and microwave breast imaging approaches. Each of the methods mentioned above has its own advantages and disadvantages. As an illustration, mammography, while widely accessible, poses the drawback of radiation exposure and may induce discomfort, particularly for women with dense breast tissue. In contrast, ultrasound is radiation-free; however, it has limitations in detecting small tumors and relies heavily on the operator's proficiency. On the other hand, Magnetic Resonance Imaging (MRI) is characterized by its heightened sensitivity, yet it comes with the trade-offs of being costlier and more time-consuming in comparison to other modalities.

[0017] Human epidermal growth factor receptor-2 (HER2 / erbB2) and CA 15-3 (MUC1) are two common used biomarkers in breast cancer detection with enzyme-linked immunoassay (ELISA). The biomarkers not only can be detected in serum but also in saliva.Numerous studies had been done with saliva samples. Belonging to a family of four transmembrane receptors, the HER2 actively participates in signal transduction pathways responsible for orchestrating cellular growth and differentiation. An upregulation or amplification of HER2 emerges as a distinctive feature associated with malignancy, signaling an unfavorable prognosis in the context of breast cancer. It has been reported that CA 15-3 in saliva carries significant diagnostic value for breast cancer. Identified as the first breast cancer-associated antigen in 1984, CA 15-3, a transmembrane glycoprotein, has drawn attention for its potential diagnostic role. Subsequent research revealed that CA 15-3 in breast secretions not only serves as a differentiator between malignant breast cancers and benign breast diseases but also proves to be a more valuable biomarker for diagnosing breast cancer when compared with mammography.

[0018] A technique with a reusable printed circuit board (PCB) containing a MOSFET and disposable single-channel test strips has been employed. The method delivers results in under 2 seconds, making it an expedited testing process. This method has also been used to detect cerebrospinal fluid (CSF), cardiac troponin I, COVID-19 and Zika virus[23’28]. Sensitivity refers to the reduction in digital readings corresponding to a one-order increase in protein concentration. Logarithmic scales offer practical utility by condensing a broad spectrum of values into a more easily comprehensible scale. The sensitivity of the HER2 strip was 70 / dec while the CA15-3 strip was 30 / dec. The limit of detection is down to 1015g / mL for both kind of strips, which is four-order lower than the commercial ELISA kits. This work significantly contributes to the field of breast cancer detection.

[0019] Enhancing the efficacy of the detection approach involves the introduction of a novel strip design known as the double-channel strip. This innovative design incorporates two distinct biomarkers, HER2 and CA 15-3, functionalized within the dual channels of the strip. This dual-biomarker approach enables simultaneous testing, thereby amplifying the precision of the rapid breast cancer test for improved accuracy. The presented circuit design enables simultaneous multi-channel measurements of the dual channels.

[0020] Biomarkers in saliva that heralded the presence of breast cancer were detected using the novel sensor with single strips and also with multi-channel strips. Initially, HER-2 was detected using HER-2 antibody-functionalized commercially available test strips, which were designed for glucose detection (Luvnshare Biomedical Inc., Hsinchu, Taiwan) without glucose enzymes, to optimize sensor sensitivity and reduce cost. FIG. 1 is an image showing repurposed glucose strips with a single channel (left with single arrow) and 3 electrodes (right with three arrows).

[0021] Binding the antibodies to attach them on the Au electrode on the strip involves a four-step functionalization procedure. FIG. 2 illustrates an example of the strip functionalization, which can include: (1) Gold plating of a carbon electrode attached to the gate pulse source on the PCB; (2) Immersion in 10mM thioglycolic acid for 4 hrs to form an Au-S bond; (3) Soaking of strips in N, N’-dicyclohexylcarbodi-imide (0.1 mM) and N- hydroxysuccinimide (0.1 mM) in acetonitrile for 2 hrs; and (4) Injection of 20 pg / ml_ of HER2, CA15-3 or CA 125 monoclonal antibody (Sino Biological Inc., Chesterbrook, PA) into the microchannel and storage of the strips in a sealed disk for 18 hours under 4°C.

[0022] To determine the limit of detection (LOD), pure HER-2, CA 15-3 and CA 125 antigen (Sino Biological Inc. Chesterbrook, PA) were diluted with artificial saliva into different concentrations. The targeted antigen was specifically recognized through corresponding antibodies anchored to the electrode on the strip. Functionalized disposable glucose strips with HER-2, CA-15-3 and CA 125 antibodies detected these proteins in doped artificial saliva down to 1 x 10’15g / ml. FIGS. 3A-3C show examples of calibration curves for plain saliva and doped saliva. Sensitivity for HER-2 biomarkers (FIG. 3A), CA-15-3 biomarkers (FIG. 3B) and CA 125 biomarkers (FIG. 3C) is down to 1015g / ml.

[0023] The sensor’s limit of detection (LOD) of 1015g / ml is six to seven orders lower than the gold standard ELISA test, which is around 108to 109g / mL, used to measure these biomarkers. The sensitivity for HER-2 is 70 / dec, CA 15-3 is 30 / dec and CA 125 is 17 / dec. The differences in sensitivity among these biomarkers is due to their molecular weights. The molecular weight for HER2 is 185 kDa, CA15-3 is 250~350 kDa, and CA 125 200-1000 kDa.A double spring model was used to simulate the output response of the sensor. The heavier proteins would have larger spring constants and diminish the detection sensitivity.

[0024] In addition to obtaining the calibration curve from a series of diluted proteins, 17 human saliva samples from both BCa patients and 4 control samples from healthy volunteers were obtained through the University of Florida Clinical and Translational Science Institute (UF CTSI) Biorepository. These de-identified samples all came with corresponding diagnoses, which were confirmed through biopsies as part of the patients’ routine care. After defrosting, the saliva samples were applied to the samples were classified into three groups: (1) healthy control; (2) in situ BCa (DCIS) and; (3) invasive BCa. Among the invasive BCa samples, one of them was HER2 positive, while the rest of the samples were HER2 negative as tested through biopsy results using immunohistochemistry (IHC). All the samples were tested with three different types of strips, which were functionalized with either HER2, CA 125 or CA15-3. All of the output digital readings were averaged from ten pulse measurements, which took around 15 msec.

[0025] FIGS. 4A-4C show examples of digital output readings of 21 human saliva samples and corresponding protein concentrations for HER-2 (FIG. 4A), CA-15-3 (FIG. 4B) and CA-125 (FIG. 4C), where there are clear differences among healthy, DCIS and invasive BCa cases based off of biomarker levels. Dotted vertical lines indicate range of ELISA LOD, which is several orders higher than the LOD for our sensor. There are several patients who have invasive and DCIS BCa who cannot be captured using the ELISA method. TABLE 1 (below) shows the median and the range of digital readings by disease status and overall p- value using Kruskal- Wallis test to examine if there is statistically significant distinctions among two or more groups. The overall p-value is significant while the value for HER2 is 0.002, indicating that this sensor technology is an efficient way to detect HER2 biomarkers in saliva. CA 125 has significant differences between healthy and invasive (p<0.05).TABLE 1. Digital readings by disease status and overall p-value.

[0026] A detection system implemented on a PCB was used to send a synchronous voltage pulse signal to both gate and drain electrode of the Metal-Oxide-Semiconductor FET (MOSFET), using a double-pulse method. FIG. 5 is an image of the PCB fabricated with a microcontroller to produce the digital sensor output. The drain pulse duration (square wave at VDD) was around 1.1 ms at a constant voltage, whereas the gate pulse started at around 40 ps after the onset of the drain pulse signal and stoped at 40 ps before the end of the drain pulse. A 13 kQ resistor was connected to the drain as a load resistor. The circuit was able to generate pulse signals and convert the analog drain output of the MOSFET into a 4- digit digital output after each pulse trigger. The analog drain waveform (VD) was collected using an Agilent infiniiVision DSO7054B oscilloscope, and a voltage reading at 750ps was extracted as the analog reading. A voltage-controlled oscillator (SN74S124N) was used to convert the drain waveform into a frequency output, and subsequently integrated by a built-in Arduino microcontroller to translate it into the 4-digit digital signal. A built-in LCD screen was used for displaying the result. Ten pulse signals were collected and averaged for each sampling concentration for the analog signal and digital readout.

[0027] A multi-channel sensing strip was developed and fabricated to allow for simultaneous detection of multiple biomarkers to enhance detection capabilities of the sensor. Each channel can be functionalized with separate antibodies for detection of biomarkers. FIG. 6 shows images (left) of a two-channel strip that allows for testing of multiple antigens in one substrate and graphical representations (right) of the underlying electrode and connecting traces for the 2-channel test strip and a 3-channel test strip. In some implementations, channels can be included on both (opposite) sides of test strip. This two-channel strip was successfully used to detect HER2 and CA-15-3 simultaneously.FIGS. 7A and 7B show examples of digital readings from the functionalized two-channel strip in FIG. 6, where HER-2 (FIG. 7A) and CA 15-3 (FIG. 7B) were detected simultaneously for each sample. These results are similar to the ones detected with single channel strips where the digital reading correlated well with the burden of disease.

[0028] To create these multi-channel strips, a process involving gold sputtering was initiated, followed by selective removal of a portion of the gold to form distinct electrodes. Each channel comprises two gold electrodes, one designed for signal input and the other for signal output. The electrodes within the channels can be functionalized for the detection of specific biomarkers. The details of the functionalization method have been previously elucidated. Anti-HER2 / ERBB2 monoclonal antibody (Sino Biological Inc., Chesterbrook, PA) and CA 15-3 monoclonal antibody (Sino Biological Inc., Chesterbrook, PA) were used during the functionalization process. In this case, all antibodies utilized underwent a rigorous validation process to confirm their specificity for binding to the targeted proteins. Furthermore, experiments were conducted using sensor strips that had been functionalized with HER2 antibodies to detect various CA 15-3 proteins and vice versa, and employing strips functionalized with CA 15-3 antibodies to identify HER2. Notably, in both cases, there was no discernible response, and the output readings closely resembled those obtained from blank saliva samples.

[0029] Human HER2 / ErbB2 / CD340(676-1255) protein (Sino Biological Inc., Chesterbrook, PA) and human Mucin-1 / MUC-1 (CA 15-3) protein (Sino Biological Inc., Chesterbrook, PA) were diluted into a series of protein standard solution to obtain the calibration curve. A total of 16 human saliva samples were sourced from both breast cancer patients and healthy volunteers, facilitated by the University of Florida Clinical and Translational Science Institute (UF CTSI) Biorepository. The specimens were collected from individuals within the UF Health System and were meticulously preserved in a deep-freeze storage unit at -78°C. All samples were de-identified and accompanied by corresponding diagnoses, which were rigorously validated through biopsy procedures conducted as part of the patients' routine medical care. After thawing the saliva samples, the samples weredirectly introduced into the microfluidic channel without the need for any dilution, filtration, or centrifugation steps. Categorizing the human samples based on their histologic type, they were distinguished into three distinct groups: (1) healthy control; (2) in situ breast cancer; and (3) invasive breast cancer. Among the invasive breast cancer samples, one was identified as HER2 positive, while the remaining samples were HER2 negative, as confirmed by immunohistochemistry (IHC) results from biopsy analyses. Tests were conducted on all the samples using the two channels on the strip, functionalized with HER2 and CA 15-3 antibodies respectively. The p-values of the testing results were analyzed by Kruskal- Wallis tests (continuous outcomes) and Fisher’s exact tests.

[0030] A PCB was designed to facilitate the conversion of voltage signals obtained from the test strips into digital readings. FIG. 8 is an image illustrating the layout of the fabricated PCB, which is described in more detail below. To amplify the detected signal from the test strip, a MOSFET (STMicroelectronics STP200N3LL) was employed. The PCB comprises, e.g., a pattern generator, reading display, strip connector, and other circuit components configured to facilitate the reading of the functionalized multi-channel test strip. The device operates by connecting the test strip to the Arduino-activated system. The Arduino triggers the pattern generator to create a test pattern, generating output signals through the strip. The readout block, equipped with a metal-oxide-semiconductor field-effect transistor (MOSFET), amplifies the signal, which is then converted to a frequency signal by a voltage- controlled oscillator (VCO). A counter measures the VCO output, providing a digital representation of the readout voltage displayed on the device. The device employs multiple test patterns for each measurement, averting charge accumulation effects on the strip. Adjustable parameters, including test pattern length and frequency, can be controlled by the Arduino and a potentiometer, ensuring adaptability to various strip types. The MOSFET's active socket allows easy replacement for optimization, emphasizing the device's flexibility and precision in concentration measurements.

[0031] To validate the reliability of the dual-channel sensor and its capability to distinguish between two distinct biomarkers, a series of tests were conducted. Each channelwas individually assessed to demonstrate the functionality of both channels. These strips were tested with varying concentrations of diluted pure HER2 protein (Sino Biological Inc., Chesterbrook, PA) and CA 15-3 (Sino Biological Inc., Chesterbrook, PA). The dilutions were prepared using pure artificial saliva (Pickering Laboratories Inc., Mountain View, CA), and the proteins were diluted from 1 x 10“15g / mL to 1 x w5g / mL. As the protein concentration rises, a concurrent increase in the gate current was observed, resulting in a proportional decrease in the output drain current. Simply put, elevated protein concentration in the sample corresponds to lower output readings.

[0032] FIG. 9A shows an example of a calibration curve of the HER2 protein, which demonstrates that the double channel strip can detect the HER2 in artificial saliva samples, with a limit of detection as low as 1 x 1O~15g / mL. The HER2 side exhibits a sensitivity of 78 / dec. FIG. 9B shows examples of the output digital reading result from the human sample test with strips functionalized by HER2 antibody. Sixteen human samples were tested with the strips to validate the technique. The digital reading shows a decline as one moves from the healthy group to the invasive breast cancer group, signifying an elevation in HER2 concentration. In situ breast cancer is an early stage where abnormal cells are confined to the milk ducts or lobules and haven't spread. Invasive breast cancer is a more advanced stage where cancer cells have invaded surrounding breast tissue, posing a greater risk of spreading to other parts of the body. Significantly, the majority of invasive breast cancer samples exhibit HER2-negativity, a determination established through Immunohistochemistry (IHC). The sensor developed in this study boasts a low limit of detection, enabling the differentiation of negative samples. This detection method proves highly effective in distinguishing between diverse sample groups, presenting substantial advantages for early detection and subsequent treatment.

[0033] In FIG. 90, an example of the calibration curve for the CA 15-3 side of the dualchannel strip is depicted. The sensitivity is approximately 56 / dec, while the limit of detection reaches as low as 1015g / mL. To underscore the relevance of the sensor, human sample testing was conducted, and examples of the output digital reading result with stripsfunctionalized by CA 15-3 antibody are illustrated in FIG. 9D. The calibration curve, coupled with the human sample test readings, provides individuals with valuable insights into their health status. A decrease in readings may warrant caution, signaling an increase in breast cancer-related biomarkers. Simultaneous testing of both biomarkers enhances the accuracy of the rapid breast cancer test, offering a comprehensive understanding of one's health.

[0034] TABLE 2 shows the analytical result of HER2 and CA 15-3 human sample test.The p-values for HER2 and CA 15-3 were 0.003 and 0.011 , respectively. Continuous variables are presented as median (range); categorical variables are presented as N (col%). P-values are the results of Kruskal-Wallis tests (continuous outcomes) and Fisher’s exact tests. In simpler terms, these values indicate the likelihood that the observed differences in the levels of HER2 and CA 15-3 between healthy individuals and cancer patients are not due to random chance. Lower p-values, such as 0.003, suggest a higher level of statistical significance, implying that the observed differences are more likely to be real and not just random variations. These p-values provide a foundation for the relevance of HER2 and CA 15-3 as potential biomarkers for distinguishing between health and cancer within the studied population.Healthy Volunteers In Situ Breast Cancer Invasive Breast p value(N=4, 25%) (N=3, 19%) Cancer(N=9, 56%)HER2 3264 (3177, 3355) 3004 (2979, 3147) 2679 (1984, 3380) 0.003CA 15-3 3196 (3129, 3350) 2874 (2849, 3179) 2770 (1988, 3293) 0.011TABLE 2. Patient characteristics and sensor readings by disease group.

[0035] The introduction of the dual-channel strip represents a significant advancement in breast cancer detection methodology. The innovative design, capable of simultaneously assessing HER2 and CA 15-3 biomarkers, enhances the precision of rapid breast cancer testing. The functionalization process, involving specific antibodies and thorough validation, ensures reliability and specificity in detecting targeted proteins. The sensitivity and low limit of detection demonstrated by the dual-channel strip, coupled with successful human sample testing, underscore its potential as a valuable diagnostic tool. The ability to differentiatebetween healthy and breast cancer samples offers a comprehensive understanding of one's health status. Completing the entire test in under 2 seconds, this technique is poised to greatly assist medical professionals in conducting breast cancer screening tests, whether in a hospital setting or public areas. The use of the dual-channel strip has the potential to enhance early detection in breast cancer.

[0036] Referring now to the multi-channel detection system, a low-power handheld pulse waveform detection system and silicon chip are proposed, as illustrated in the schematic diagram of FIG. 10A. In the system, a microcontroller (MCU) can be integrated to control other components in the circuit, generate pulses with adjustable periods, digitize readout signals, and facilitate wireless Bluetooth communication with a smart phone. A level shifter and a digital-to-analog converter (DAC) can adjust the pulse voltage generated by the MCU, allowing flexible adjustment of the pulse voltage and period according to experimental needs. The applied voltage pulses can be switched to specific channels, enabling simultaneous multi-channel measurements. The measurement parameters for each channel can be independently configured and optimized for different target substances. When there is no measurement signal, the switch can be toggled to a ground connection to prevent charge accumulation on the electrodes, avoiding interference with the measurement values.

[0037] The signal can be processed through a closed-loop programmable gain amplifier (PGA), illustrated in FIG. 10B. Traditional common-source amplifier architectures encounter challenges such as non-linearity, restricted input range, and cumbersome gain reconfiguration, mainly stemming from the FET's operational characteristics. Utilizing an Op Amp-based closed-loop amplifier mitigates these issues. By employing an appropriate amplifier topology, enhancements in input range and linearity can be achieved. Moreover, the readout circuit's gain is easily adjustable by tuning the feedback resistor ratio. FIG. 10C is a plot illustrating an example of the readout data of the two topologies, demonstrating that the Op Amp-based architecture has a better linearity.

[0038] Additional pins are available at the strip interface, providing a low-cost implementation of automatic strip recognition and the ability to switch measurement settingsby adding identification pins on the sample. FIG. 10D illustrates the example of electrode recognition pins. For instance, with three recognition pins, the leftmost pin remains at a high voltage, and the potential input from the other two pins can identify the inserted sample type.

[0039] Furthermore, the system includes two indicator lights that can quickly provide users with reference results based on the measured values, with a green or red light indicating high or low values, respectively.

[0040] This system can include a corresponding application / software designed for controlling measurement parameters and displaying results. The main interface of the application can be configured to display the inserted sample types along with the measured values for each channel. Multiple measurements can be taken for each channel, and the results are presented on this page, including the calculated average for each channel. In the application, optimal measurement parameters can be configured for different substances, such as name, pulse voltage, PGA reference voltage, pulse width, pulse interval, measurement timing, number of measurements, PGA gain, and the use of LED indicator lights.

[0041] Once the measurement parameters for the target substance are set, users can assign specific parameters for each channel based on the measurable substances on each sample. When a sample is inserted, the system can automatically identify its type based on the recognition pins and switch to the corresponding measurement parameters.

[0042] Breast cancer remains a significant and pressing health concern, impacting a considerable number of individuals annually. This disclosure presented an innovative approach to breast cancer detection through the use of dual-channel test strips that can concurrently evaluate two prominent biomarkers — HER2 and CA 15-3. The limit of detection for both biomarkers is as low as 1015g / mL, which is four orders of magnitude lower than that of commercial enzyme-linked immunoassay (ELISA) kits. The sensor exhibits impressive sensitivity, with 78 / dec forthe HER2 side and 56 / dec for the CA 15-3 side. To validate the efficacy of the dual-channel strip, human sample tests were conducted, demonstrating its ability to differentiate between healthy and cancer groups. The results indicate significant pvalues for HER2 and CA 15-3 tests, emphasizing the importance of this research. Notably, the testing process takes less than 2 seconds. The results show a promising avenue for rapid and accurate breast cancer detection, providing valuable insights for early diagnosis and subsequent treatment.

[0043] It should be emphasized that the above-described embodiments of the present disclosure are merely possible examples of implementations set forth for a clear understanding of the principles of the disclosure. Many variations and modifications may be made to the above-described embodiment(s) without departing substantially from the spirit and principles of the disclosure. All such modifications and variations are intended to be included herein within the scope of this disclosure and protected by the following claims.

[0044] The term "substantially" is meant to permit deviations from the descriptive term that don't negatively impact the intended purpose. Descriptive terms are implicitly understood to be modified by the word substantially, even if the term is not explicitly modified by the word substantially.

[0045] It should be noted that ratios, concentrations, amounts, and other numerical data may be expressed herein in a range format. It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a concentration range of “about 0.1% to about 5%” should be interpreted to include not only the explicitly recited concentration of about 0.1 wt% to about 5 wt%, but also include individual concentrations (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.5%, 1.1%, 2.2%, 3.3%, and 4.4%) within the indicated range. The term “about” can include traditional rounding according to significant figures of numerical values. In addition, the phrase “about ‘x’ to ‘y’” includes “about ‘x’ to about ‘y’”.

Claims

CLAIMSTherefore, at least the following is claimed:1 . A medical sensing system, comprising: a portable sensing and readout device comprising: a test strip port configured to detachably engage with a disposable multi-channel test strip, each channel of the multi-channel test strip comprising a functionalized sensing area configured to detect an agent different than other channels of the multi-channel test strip; pulse generation circuitry configured to generate synchronized gate and drain pulses; and switching circuitry configured to control application of the synchronized gate and drain pulses to individual channels of the multi-channel test strip for measurement, where the switching circuitry electrically couples a first electrode of an individual channel being measured to a gate pulse output of the pulse generation circuitry.

2. The medical sensing system of claim 1 , comprising the multi-channel test strip including a plurality of channels.

3. The medical sensing system of claim 1 , wherein the multi-channel test strip is a three-channel test strip.

4. The medical sensing system of claim 1 , wherein the multi-channel test strip comprises a first set of channels on a first side and a second set of channels on a second side.

5. The medical sensing system of claim 1 , wherein the multi-channel test strip comprises two channels functionalized with different antibodies for detection of biomarkers.

6. The medical sensing system of claim 5, wherein a first channel of the multi-channel test strip is functionalized to detect HER2 and a second channel of the multi-channel test strip is functionalized to detect CA 15-3.

7. The medical sensing system of claim 1 , wherein the functionalized sensing area of each channel comprises two electrodes separated from each other, wherein at least one electrode is functionalized to detect the agent.

8. The medical sensing system of claim 1 , wherein the switching circuitry electrically couples one or more individual channel not being measured to ground.

9. The medical sensing system of claim 1 , wherein the pulse generation circuitry is configured to adjust the gate pulse.

10. The medical sensing system of claim 9, wherein the pulse generation circuitry comprises a level shifter to adjust voltage of the gate pulse.11 . The medical sensing system of claim 1 , wherein the pulse generation circuitry is configured to adjust the gate period.

12. The medical sensing system of claim 1 , wherein the portable sensing and readout device comprises an adjustable gain amplifier to measure an output.

13. The medical sensing system of claim 12, wherein the adjustable gain amplifier is a closed-loop programmable gain amplifier.

14. The medical sensing system of claim 1 , wherein the multi-channel test strip comprises a combination of pins providing an identification sequence corresponding to the multi-channel test strip.

15. The medical sensing system of claim 14, wherein the test strip port is configured to engage with the combination of pins and the portable sensing and readout device is configured to identify measurement parameters associated with the multi-channel test strip based upon the combination of pins.

16. The medical sensing system of claim 1 , comprising LED indicators configured to provide visual indications of measurement results.

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