Optimized Lateral Flow Immunoassay Reader for the Detection of Infectious Diseases in Developing Countries

Detection and control of infectious diseases is a major problem, especially in developing countries. Lateral flow immunoassays can be used with great success for the detection of infectious diseases. However, for the quantification of their results an electronic reader is required. This paper presents an optimized handheld electronic reader for developing countries. It features a potentially low-cost, low-power, battery-operated device with no added optical accessories. The operation of this proof of concept device is based on measuring the reflected light from the lateral flow immunoassay and translating it into the concentration of the specific analyte of interest. Characterization of the surface of the lateral flow immunoassay has been performed in order to accurately model its response to the incident light. Ray trace simulations have been performed to optimize the system and achieve maximum sensitivity by placing all the components in optimum positions. A microcontroller enables all the signal processing to be performed on the device and a Bluetooth module allows transmission of the results wirelessly to a mobile phone app. Its performance has been validated using lateral flow immunoassays with influenza A nucleoprotein in the concentration range of 0.5 ng/mL to 200 ng/mL

Neuromodulators for Primary Headache Disorders: A Review

Primary headache disorders are among the most common and disabling globally. Pharmacological treatments are often insufficient, poorly tolerated, have side effects and the majority of patients are unable to complete their treatment. Understanding the neural pain pathways of these disorders has led to the development of alternative therapies. Electrical nerve stimulation is a form of pain modulation with few side effects for the treatment of primary headache disorders. Different neuromodulation approaches, both invasive and non-invasive, have rapidly led to new approaches for the treatment of patients suffering from headache, particularly those who have failed traditional pharmacotherapy. Non-invasive treatment methods are safe, practical and well-tolerated compared to alternatives. This paper details recent evidence-based advances in neuromodulators for primary headache disorders such as migraine and trigeminal autonomic cephalalgias (in particular, cluster headache) including non-invasive commercial devices used for migraine and cluster headache. The target neural structures, their advantages and disadvantages and their application in headache treatment are discussed. Examples of using neuromodulation to manage primary headache disorders are discussed. Both invasive stimulations e.g. of occipital and vagus nerves, the sphenopalatine ganglion, deep brain and spinal cord, and non-invasive, e.g. stimulation of the frontal, cervical and auricular vagus nerves, transcranial magnetic and transcranial direct current stimulation, are detailed

Direct Numerical Simulations of premixed methane flame initiation by pilot n-heptane spray autoignition

Autoignition of n-heptane sprays in a methane/air mixture and the subsequent methane premixed flame ignition, a constant volume configuration relevant to pilot-ignited dual fuel engines, was investigated by DNS. It was found that reducing the pilot fuel quantity, increases its autoignition time. This is attributed to the faster disappearance of the most reactive mixture fraction (predicted from homogeneous reactor calculations) which is quite rich. Consequently, ignition of the n-heptane occurs at leaner mixtures. The premixed methane flame is eventually ignited due to heating gained by the pressure rise caused by the n-heptane oxidation, and heat and mass transfer of intermediates from the n-heptane autoignition kernels. For large amounts of the pilot fuel, the combustion of the n-heptane results in significant adiabatic compression of the methane–air mixture. Hence the slow methane oxidation is accelerated and is further promoted by the presence of species in the oxidizer stream originating from the already ignited regions. For small amounts of the pilot fuel intermediates reach the oxidizer stream faster due to the very lean mixtures surrounding the n-heptane ignition kernels. Therefore, the premixed methane oxidation is initiated at intermediate temperatures. Depending on the amount of n-heptane, different statistical behaviour of the methane oxidation is observed when this is investigated in a reaction progress variable space. In particular for large amounts of n-heptane the methane oxidation follows roughly an autoignition regime, whereas for small amounts of n-heptane methane oxidation is similar to a canonical premixed flame. The data can be used for validation of various turbulent combustion models for dual-fuel combustion.The computational costs for this work were covered by the EPSRC project ref. no. EP/J021997/1.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.combustflame.2015.09.01

Impact of neuroanatomical variations and electrode orientation on stimulus current in a device for migraine: a computational study

Objective. Conventional treatment methods for migraine often have side effects. One treatment involves a wearable neuromodulator targeting frontal nerves. Studies based on this technique have shown limited efficacy and the existing setting can cause pain. These may be associated with neuroanatomical variations which lead to high levels of required stimulus current. The aim of this paper is to study the effect of such variations on the activation currents of the Cefaly neuromodulator. Also, using a different electrode orientation, the possibility of reducing activation current levels to avoid painful side-effects and improve efficacy, is explored. Approach. This paper investigates the effect of neuroanatomical variations and electrode orientation on the stimulus current thresholds using a computational hybrid model involving a volume conductor and an advanced nerve model. Ten human head models are developed considering statistical variations of key neuroanatomical features, to model a representative population. Main results. By simulating the required stimulus current level in the head models, it is shown that neuroanatomical variations have a significant impact on the outcome, which is not solely a function of one specific neuroanatomical feature. The stimulus current thresholds based on the conventional Cefaly system vary from 4.4 mA to 25.1 mA across all head models. By altering the electrode orientation to align with the nerve branches, the stimulus current thresholds are substantially reduced to between 0.28 mA and 15 mA, reducing current density near pain-sensitive structures which may lead to a higher level of patient acceptance, further improving the efficacy. Significance. Computational modeling based on statistically valid neuroanatomical parameters, covering a representative adult population, offers a powerful tool for quantitative comparison of the effect of the position of stimulating electrodes which is otherwise not possible in clinical studies

Compact pixel architecture for CMOS lateral flow immunoassay readout systems

A novel pixel architecture for CMOS image sensors is presented. It uses only one amplifier for both integration of the photocurrent and in-pixel noise cancelation, thus minimizing power consumption. The circuit is specifically designed to be used in readout systems for lateral flow immunoassays. In addition a switching technique is introduced enabling the use of column correlated double sampling technique in capacitive transimpedance amplifier pixel architectures without the use of any memory cells. As a result the reset noise which is crucial in these architectures can be suppressed. The circuit has been designed in a 0.35-μm CMOS technology and simulations are presented to show its performance

1.2V Energy-Efficient Wireless CMOS Potentiostat for Amperometric Measurements

Wireless biosensors are playing a pivotal role in health monitoring, disease detection and management. The development of wireless biosensor nodes and networks strongly relies on the design of novel low-power, low-cost and flexible CMOS sensor readouts. This paper presents a CMOS potentiostat that integrates a control amplifier, a dual-slope ADC and a wireless unit on the same chip. It implements a novel time-based readout scheme, whereby the counter of the dual-slope ADC is moved to the receiver and the sensor current is encoded in the timing between two wireless pulses transmitted via pulse-harmonic modulation across an inductive link. Measured results show that the potentiostat chip can resolve a minimum input current of 10pA at a sampling frequency of 125 Hz and a power consumption of 12 μW

Direct Numerical Simulations of Dual-Fuel Non-Premixed Autoignition

Autoignition of turbulent methane/air mixing layers, in which n-heptane droplets have been added, was investigated by DNS. This configuration is relevant to dual-fuel, pilot-ignited natural gas engines under direct injection conditions. Two passive scalars were introduced in order to describe the dual fuel combustion. It was shown that the pre-ignition phase is dominated by n-heptane oxidation while methane oxidation is less intense. During the pre-ignition phase the methane/air mixing layer is distorted due to turbulence creating regions around the n-heptane droplets allowing the transport of intermediate species to the methane reaction zone. According to the passive scalars introduced, it was shown that ignition occurs at mixtures rich in n-heptane vapour. Subsequently, consumption of both n-heptane and methane is rapidly increased and promoted by the high temperatures achieved. The competition of the two fuels makes autoignition retarded relative to the pure n-heptane case, but accelerated relative to the pure methane case.This is the author accepted manuscript. The final version is available from Taylor & Francis via http://dx.doi.org/10.1080/00102202.2016.113939

Effect of Model Complexity on Fiber Activation Estimates in a Wearable Neuromodulator for Migraine

Migraine is a prevalent and highly disabling disorder. The pharmaceutical and invasive treatment methods have trouble-some side effects and associated risks, hence undesirable. Transcutaneous supraorbital neuromodulation has been shown to potentially suppress episodic migraine attacks yet results have low efficacy. This inconclusive response may be associated with neuroanatomical variations of patients which may be investigated using computational models. Model complexity is a limiting factor in implementing such techniques. This paper investigates the effect of model complexity on fiber activation estimates in transcutaneous frontal nerve stimulation. It is shown that the model can be simplified while minimally affecting the outcome

Computational Study on Transcutaneous Frontal Nerve Stimulation: Simplification of Human Head Model

Migraine is a highly disabling disorder of the brain which may affect patients both socially and economically. The pharmaceutical and invasive treatment methods may have undesirable side effects and associated risks. It has recently been shown that transcutaneous supraorbital neuromodulation may suppress episodic migraine attacks. However, results have indicated low efficacy. This inconclusive response may be associated with neuro-anatomical variations in patients which may be investigated using computational models. Model complexity is a limiting factor in implementing such techniques. This paper investigates the effect of model complexity on fiber activation estimates in transcutaneous frontal nerve stimulation. It is shown that the model can be simplified while minimally affecting the outcome

Influence of cellular structures of skin on fiber activation thresholds and computation cost

Electrical neuromodulation is widely used to treat and manage neurological disorders. Migraine, a socioeconomic burden, may be treated using this technique. Transcutaneous stimulation of frontal nerves by electrodes placed on the forehead is of interest as it exposes patients to lower levels of risk and side-effects compared with surgical and pharmaceutical solutions and may be readily delivered. The size, shape and placement of the electrodes can be optimised using computational models involving a volume conductor model of anatomical structures and electrodes as well as nerve fibre models. A detailed volume conductor incorporating cell level structures of skin can yield an accurate map of electrical potential distribution due to an electrode setting. However, such a model imposes a very substantial computational cost which may impede the design process. Computation cost can be significantly reduced if the skin microscopic structures are ignored. In this study, we compare the accuracy and computation cost with and without skin microscopic structures on the outcome of a device for transcutaneous frontal nerve stimulation. The performance is presented as the percentage activation of target nerve fibres in response to the level of stimulus current delivered via surface electrodes placed on the forehead. When cell level structures of skin are not incorporated, discretisation time is reduced from 21 h to 0.4 h and the number of finite elements used from 18 M to 1.4 M. Only 1% difference in stimulus current thresholds is observed