Publications
24 results found
Cavallo FR, Mirza KB, de Mateo S, et al., 2022, A Point-of-Care Device for Fully Automated, Fast and Sensitive Protein Quantification via qPCR, BIOSENSORS-BASEL, Vol: 12
Kumar P, Mirza KB, Choudhury K, et al., 2021, Tissue Regeneration through Cyber-Physical Systems and Microbots, ADVANCED FUNCTIONAL MATERIALS, Vol: 31, ISSN: 1616-301X
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- Citations: 3
Cavallo FR, Mirza KB, de Mateo S, et al., 2021, Aptasensor for quantification of leptin through PCR amplification of short DNA-aptamers., ACS Sensors, Vol: 6, Pages: 709-715, ISSN: 2379-3694
Protein quantification is traditionally performed through enzyme-linked immunosorbent assay (ELISA), which involves long preparation times. To overcome this, new approaches use aptamers as an alternative to antibodies. In this paper, we present a new approach to quantify proteins with short DNA aptamers through polymerase chain reaction (PCR) resulting in shorter protocol times with comparatively improved limits of detection. The proposed method includes a novel way to quantify both the target protein and the corresponding short DNA-aptamers simultaneously, which also allows us to fully characterize the performance of aptasensors. Human leptin is used as a target protein to validate this technique, because it is considered an important biomarker for obesity-related studies. In our experiments, we achieved the lowest limit of detection of 100 pg/mL within less than 2 h, a limit affected by the dissociation constant of the leptin aptamer, which could be improved by selecting a more specific aptamer. Because of the simple and inexpensive approach, this technique can be employed for Lab-On-Chip implementations and for rapid "on-site" quantification of proteins.
Han Z, Francesca C, Nikolic K, et al., 2021, Signal identification of DNA amplification curves in custom-PCR platforms, ISSN: 0271-4310
Custom-made, point-of-care PCR platforms are a necessary tool for rapid, point-of-care diagnostics in situations such as the current Covid-19 pandemic. However, a common issue faced by them is noisy fluorescence signals, which consist of a drifting baseline or noisy sigmoidal curve. This makes automated detection difficult and requires human verification. In this paper, we have tried to use nonlinear fitting for automated classification of PCR waveforms to identify whether amplification has taken place or not. We have presented several novel signal reconstruction techniques based on nonlinear fitting which will enable better pre-processing and automated differentiation of a valid or invalid PCR amplification curve. We have also tried to perform this classification at lower PCR cycles to reduce decision times in diagnostic tests.
Han Z, Francesca C, Nikolic K, et al., 2021, Signal Identification of DNA Amplification Curves in Custom-PCR Platforms, IEEE International Symposium on Circuits and Systems (IEEE ISCAS), Publisher: IEEE, ISSN: 0271-4302
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- Citations: 5
Cavallo FR, Mirza KB, de Mateo S, et al., 2021, A Point-of-Care Device for Sensitive Protein Quantification, IEEE International Symposium on Circuits and Systems (IEEE ISCAS), Publisher: IEEE, ISSN: 0271-4302
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- Citations: 2
Wildner K, Mirza KB, De La Franier B, et al., 2020, Iridium oxide based potassium sensitive microprobe with anti-fouling properties, IEEE Sensors Journal, Vol: 20, Pages: 12610-12619, ISSN: 1530-437X
Here, we present a new type of potassium sensor which possesses a combination of potassium sensing and anti-biofouling properties. Two major advancements were required to be developed with respect to the current technology; Firstly, design of surface linkers for this type of coating that would allow deposition of the potassiumselective coating on Iridium (Ir) wire or micro-spike surface for chronic monitoring for the first time. As this has never been done before, even for flat Ir surfaces, the material’s small dimensions and surface area render this challenging. Secondly, the task of transformation of the coated wire into a sensor. Here we develop and bench-test the electrode sensitivity to potassium and determine its specificity to potassium versus sodium interference. For this purpose we also present a novel characterisation platform which enables dynamic characterization of the sensor including step and sinusoidal response to analyte changes. The developed sensor shows good sensitivity (<1 mM concentrations of K+ ions) and selectivity (up to approximately 10 times more sensitive to K+ than Na+ concentration changes, depending on concentrations and ionic environment). In addition, the sensor displays very good mechanical properties for the small diameter involved (sub 150 μm), which in combination with anti-biofouling properties, renders it an excellent potential tool for the chemical monitoring of neural and other physiological activities using implantable devices.
Roever P, Mirza KB, Nikolic K, et al., 2020, Convolutional neural network for classification of nerve activity based on action potential induced neurochemical signatures, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 1-5, ISSN: 0271-4302
Neural activity results in chemical changes in theextracellular environment such as variation in pH or potassium/sodium ion concentration. Higher signal to noise ratio makeneurochemical signals an interesting biomarker for closed-loopneuromodulation systems. For such applications, it is importantto reliably classify pH signatures to control stimulationtiming and possibly dosage. For example, the activity of thesubdiaphragmatic vagus nerve (sVN) branch can be monitoredby measuring extracellular neural pH. More importantly, guthormone cholecystokinin (CCK)-specific activity on the sVN canbe used for controllably activating sVN, in order to mimic thegut-brain neural response to food intake. In this paper, we presenta convolutional neural network (CNN) based classification systemto identify CCK-specific neurochemical changes on the sVN,from non-linear background activity. Here we present a novelfeature engineering approach which enables, after training, ahigh accuracy classification of neurochemical signals using CNN.
Cheng R, Mirza KB, Nikolic K, 2020, Neuromorphic robotic platform with visual input, processor and actuator, based on spiking neural networks, Applied System Innovation, Vol: 3, Pages: 1-16, ISSN: 2571-5577
This paper describes the design and modus of operation of a neuromorphic robotic platform based on SpiNNaker, and its implementation on the goalkeeper task. The robotic system utilises an address event representation (AER) type of camera (dynamic vision sensor (DVS)) to capture features of a moving ball, and a servo motor to position the goalkeeper to intercept the incoming ball. At the backbone of the system is a microcontroller (Arduino Due) which facilitates communication and control between different robot parts. A spiking neuronal network (SNN), which is running on SpiNNaker, predicts the location of arrival of the moving ball and decides where to place the goalkeeper. In our setup, the maximum data transmission speed of the closed-loop system is approximately 3000 packets per second for both uplink and downlink, and the robot can intercept balls whose speed is up to 1 m/s starting from the distance of about 0.8 m. The interception accuracy is up to 85%, the response latency is 6.5 ms and the maximum power consumption is 7.15 W. This is better than previous implementations based on PC. Here, a simplified version of an SNN has been developed for the ‘interception of a moving object’ task, for the purpose of demonstrating the platform, however a generalised SNN for this problem is a nontrivial problem. A demo video of the robot goalie is available on YouTube.
Mirza KB, Golden C, Nikolic K, et al., 2019, Closed-loop implantable therapeutic neuromodulation systems based on neurochemical monitoring, Frontiers in Neuroscience, Vol: 13, ISSN: 1662-4548
Closed-loop or intelligent neuromodulation allows adjustable, personalised neuromodulation which usually incorporates the recording of a biomarker, followed by implementation of an algori5 thm which decides the timing (when ?) and strength (how much ?) of stimulation. Closed-loop neuromodulation has been shown to have greater benefits compared to open-loop neuromodu lation, particularly for therapeutic applications such as pharmacoresistant epilepsy, movement disorders and potentially for psychological disorders such as depression or drug addiction. How ever, an important aspect of the technique is selection of an appropriate, preferably neural biomarker. Neurochemical sensing can provide high resolution biomarker monitoring for various neurological disorders as well as offer deeper insight into neurological mechanisms. The chemicals of interest being measured, could be ions such as potassium (K+), sodium (Na+ 12 ), calcium(Ca2+), chloride (Cl−), hydrogen (H+ 13 ) or neurotransmitters such as dopamine, serotonin and glutamate. This review focusses on the different building blocks necessary for a neurochemi cal, closed-loop neuromodulation system including biomarkers, sensors and data processing algorithms. Furthermore, it also highlights the merits and drawbacks of using this biomarker modality.
Mirza KB, Kulasekeram N, Liu Y, et al., 2019, System on chip for closed loop neuromodulation based on dual mode biosignals, 2019 IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: Institute of Electrical and Electronics Engineers (IEEE), ISSN: 2158-1525
Closed loop neuromodulation, where the stimulation is controlled autonomously based on physiological events, has been more effective than open loop techniques. In the few existing closed loop implementations which have a feedback, indirect non-neurophysiological biomarkers have been typically used (e.g. heart rate, stomach distension). Although these biomarkers enable automatic initiation of neural stimulation, they do not enable intelligent control of stimulation dosage. In this paper, we present a novel closed loop neuromodulation System-on-Chip (SoC) based on a dual signal mode that is detecting both electrical and chemical signatures of neural activity. We use vagus nerve stimulation (VNS) as a design case here. Vagal chemical (pH) signal is detected and used for initiating VNS and vagal compound nerve action potential (CNAP) signals are used to determine the stimulation dosage and pattern. Although we used the paradigm of appetite control and neurometabolic therapies for developing the algorithms for neurostimulation control, the SoC described here can be utilised for other types of closed loop neuromodulation implants.
Cavallo FR, Mirza KB, Toumazou C, 2018, Links Between DNA-Based Diet and Salivary Leptin Hormone Concentration, IEEE Biomedical Circuits and Systems Conference (BioCAS) - Advanced Systems for Enhancing Human Health, Publisher: IEEE, Pages: 547-550, ISSN: 2163-4025
Kulasekeram N, Wildner K, Mirza KB, et al., 2018, Reconfigurable Low-noise Multichannel Amplifier for Neurochemical Recording, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, ISSN: 0271-4302
Wildner K, Kulasekeram N, Mirza KB, et al., 2018, Live Demo: Reconfigurable Low-noise Multichannel Amplifier for Neurochemical Recording, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, ISSN: 0271-4302
Ahmed T, Mirza KB, Nikolic K, 2018, Resource efficient pre-processor for drift removal in neurochemical signals, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, ISSN: 0271-4302
A necessary requirement for chemometric platforms is pre-processing of the acquired chemical signals to remove baseline drift in the signal. The drift could originate from sensor characteristics or from background chemical activity in the surrounding environment. A recent emerging field is neurochemical monitoring to detect and quantify neural activity. In this paper, a resource efficient pre-processing system is presented to remove drift from the acquired neurochemical signal. The drift removal technique is based on baseline manipulation without requiring window based processing. The target application, for demonstration purposes, is the recording of vagal pH signals to enable closed-loop Vagus Nerve Stimulation (VNS). The final design is multiplier-free and results in an Application Specific Integrated Circuit (ASIC) that is 640 μm by 625 μm in area.
Mirza K, Alenda A, Eftekhar A, et al., 2018, Influence of cholecystokinin-8 on compound nerve action potentials from ventral gastric vagus in rats, International Journal of Neural Systems, Vol: 28, ISSN: 0129-0657
Objective:Vagus Nerve Stimulation (VNS) has shown great promise as a potential therapy for anumber of conditions, such as epilepsy, depression and forNeurometabolic Therapies, especially fortreating obesity. The objective of this study was to characterise the left ventral subdiaphragmaticgastric trunk of vagus nerve (SubDiaGVN) and to analyse the influence of intravenous injection of guthormone cholecystokinin octapeptide (CCK-8) on compound nerve action potential (CNAP) observedon the same branch, with the aim of understanding the impact of hormones on VNS and incorporatingthe methods and results into closed loop implant design.Methods:The cervical region of the left vagus nerve (CerVN) of male Wistar rats was stimulatedwith electric current and the elicited CNAPs were recorded on the SubDiaGVN under four differentconditions:Control(no injection),Saline,CCK1(100 pmol/kg) andCCK2(1000 pmol/kg) injections.Results:We identified the presence of Aδ, B, C1, C2, C3 and C4 fibres with their respective velocityranges. Intravenous administration of CCKin vivoresults in selective, statistically significant reductionof CNAP components originating from A and B fibres, but with no discernible effect on the C fibresinn=7animals. The affected CNAP components exhibit statistically significant (pSaline−CCK1= 0.02andpSaline−CCK2= 0.007) higher normalized stimulation thresholds.Conclusion:This approach of characterising the vagus nerve can be used in closed loop systems todeterminewhento initiate VNS and also to tune the stimulation dose, which is patient specific andchanges over time.
Cork SC, Eftekhar A, Mirza KB, et al., 2018, Extracellular pH monitoring for use in closed-loop vagus nerve stimulation, Journal of Neural Engineering, Vol: 15, Pages: 1-11, ISSN: 1741-2552
Objective: Vagal nerve stimulation (VNS) has shown potential benefits for obesity treatment; however, current devices lack physiological feedback, which limit their efficacy. Changes in extracellular pH (pHe) have shown to be correlated with neural activity, but have traditionally been measured with glass microelectrodes, which limit their in vivo applicability. Approach. Iridium oxide has previously been shown to be sensitive to fluctuations in pH and is biocompatible. Iridium oxide microelectrodes were inserted into the subdiaphragmatic vagus nerve of anaesthetised rats. Introduction of the gut hormone cholecystokinin (CCK) or distension of the stomach was used to elicit vagal nerve activity. Main results. Iridium oxide microelectrodes have sufficient pH sensitivity to readily detect changes in pHe associated with both CCK and gastric distension. Furthermore, a custom-made Matlab script was able to use these changes in pHe to automatically trigger an implanted VNS device. Significance. This is the first study to show pHe changes in peripheral nerves in vivo. In addition, the demonstration that iridium oxide microelectrodes are sufficiently pH sensitive as to measure changes in pHe associated with physiological stimuli means they have the potential to be integrated into closed-loop neurostimulating devices.
Mirza KB, Zuliani C, Hou B, et al., 2017, Injection moulded microneedle sensor for real-time wireless pH monitoring, 39th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC), Publisher: IEEE, Pages: 189-192, ISSN: 1094-687X
This paper describes the development of an array of individually addressable pH sensitive microneedles using injection moulding and their integration within a portable device for real-time wireless recording of pH distributions in biological samples. The fabricated microneedles are subjected to gold patterning followed by electrodeposition of iridium oxide to sensitize them to 0.07 units of pH change. Miniaturised electronics suitable for the sensors readout, analog-to-digital conversion and wireless transmission of the potentiometric data are embodied within the device, enabling it to measure real-time pH of soft biological samples such as muscles. In this paper, real-time recording of the cardiac pH distribution, during ischemia followed by reperfusion cycles in cardiac muscles of male Wistar rats has been demonstrated by using the microneedle array.
Mirza KB, Kulasekeram N, Toumazou C, 2017, Current feedback neural amplifier with real time electrode offset suppression, International Midwest Symposium on Circuits and Systems (MWSCAS), Publisher: IEEE, Pages: 1077-1080, ISSN: 1548-3746
This paper describes a direct coupled neural amplifier with active electrode offset suppression in order to avoid large coupling capacitors and complex chopper circuits. It describes a novel feedback scheme, where a low pass current mode feedback is applied to a regulated telescopic cascode amplifier, at the cascode nodes by using a modified transconductance block. This solution leads to fully differential input-differential output direct coupled neural amplifier, achieving a DC offset suppression range of ±200 mV, a chip area of 0.078 mm 2 per channel and an input referred noise of 2.5 μV rms over 1 Hz-5kHz bandwidth.
Mirza KB, Kulasekeram N, Cork S, et al., 2017, Platform for Closed Loop Neuromodulation Based on Dual Mode Biosignals
<jats:title>Abstract</jats:title><jats:p>Closed loop neuromodulation, where the stimulation is controlled autonomously based on physiological events, has been more effective than open loop techniques. In the few existing closed loop implementations which have a feedback, indirect non-neurophysiological biomarkers have been typically used (e.g. heart rate, stomach distension). Although these biomarkers enable automatic initiation of neural stimulation, they do not enable intelligent control of stimulation dosage. In this paper, we present a novel closed loop neuromodulation platform based on a dual signal mode that is detecting electrical and chemical signatures of neural activity. We demonstrated it on a case of vagus nerve stimulation (VNS). Vagal chemical (pH) signal is detected and used for initiatisng VNS and vagal compound action potential (CAP) signals are used to determine the stimulation dosage and pattern. Although we used the paradigm of appetite control and neurometabolic therapies, the platform developed here can be utilised for prototyping closed loop neuromodulation systems before adapting the final System-on-Chip (SoC) design.</jats:p>
Mirza K, Zuliani C, Hou B, et al., 2017, An Individually Addressable Microneedle Device for Real-Time Wireless pH Monitoring, 9th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC'17)
This paper describes the development of an array of individually addressable pH sensitive microneedles using injection moulding and their integration within a portable device for real-time wireless recording of pH distributions in biological samples. The fabricated microneedles are subjected to gold pat- terning followed by electrodeposition of iridium oxide to sensitize them to 0.07 units of pH change. Miniaturised electronics suitable for the sensors readout, analog-to-digital conversion and wireless transmission of the potentiometric data are embodied within the device, enabling it to measure real-time pH of soft biological samples such as muscles. In this paper, real-time recording of the cardiac pH distribution, during ischemia followed by reperfusion cycles in cardiac muscles of male Wistar rats has been demonstrated by using the microneedle array.
Mirza K, Zuliani C, Hou B, et al., 2017, An Individually Addressable Microneedle Device for Real-Time Wireless pH Monitoring, 39th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC'17)
This paper describes the development of an array of individually addressable pH sensitive microneedles using injection moulding and their integration within a portable device for real-time wireless recording of pH distributions in biological samples. The fabricated microneedles are subjected to gold pat- terning followed by electrodeposition of iridium oxide to sensitize them to 0.07 units of pH change. Miniaturised electronics suitable for the sensors readout, analog-to-digital conversion and wireless transmission of the potentiometric data are embodied within the device, enabling it to measure real-time pH of soft biological samples such as muscles. In this paper, real-time recording of the cardiac pH distribution, during ischemia followed by reperfusion cycles in cardiac muscles of male Wistar rats has been demonstrated by using the microneedle array.
Mirza KB, Wildner K, Kulasekeram N, et al., 2017, Live Demo: Platform for Closed Loop Neuromodulation Based on Dual Mode Biosignals, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, ISSN: 2163-4025
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- Citations: 2
Mirza KB, Luan S, Constandinou TG, 2012, Towards a Fully-Integrated Solution for Capacitor-Based Neural Stimulation, International Symposium on Circuits and Systems (ISCAS), ISSN: 0271-4302
Charge-mode stimulation (ChgMS) is a relatively new method being explored in the field of electrical neural stimulation. One of the key challenges in such a system is to overcome charge sharing between the storage capacitor and the double layer capacitor in the Electrode-Electrolyte-Interface (EEI). In this work, this issue is overcome by using a second-generation negative current conveyor (CCII-) with low current tracking error. The level of charge sharing in the circuit is expressed by a new figure of merit (charge delivery efficiency) introduced in this paper. The proposed system has a maximum power efficiency of 76.6% and a total power consumption of 270uW per electrode for a target charge stimulus of 0.9nC. Crucially, the system achieves a minimum charge delivery efficiency of 98.22%.
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