scholarly journals Time-domain signal averaging to improve microparticles detection and enumeration accuracy in a microfluidic impedance cytometer

Author(s):  
Brandon Ashley ◽  
Umer Hassan

Microfluidic impedance cytometry is a powerful system to measure micro and nano-sized particles and is routinely used in point-of-care settings disease diagnostics and other biomedical applications. However, small objects near a sensor’s detection limit are plagued with relatively significant background noise and are difficult to identify for every case. While many data processing techniques can be utilized to reduce noise and improve signal quality, frequently they are still inadequate to push sensor detection limits. Here, we report the first demonstration of a novel signal averaging algorithm effective in noise reduction of microfluidic impedance cytometry data, improving enumeration accuracy and reducing detection limits. Our device uses a 22 μm tall microchannel and gold coplanar microelectrodes that generates an electric field, recording bipolar pulses from polystyrene microparticles flowing through the channel. In addition to outlining a modified moving signal averaging technique theoretically and with a model dataset, we also performed a compendium of characterization experiments including variations in flow rate, input voltage, and particle size. Multi-variate metrics from each experiment are compared including signal amplitude, pulse width, background noise, and signal-to-noise ratio (SNR). Incorporating our technique resulted in improved SNR and counting accuracy across all experiments conducted, and the limit of detection improved from 5 μm to 1 μm particles without modifying microchannel dimensions. Succeeding this, we envision implementing our modified moving average technique to develop next generation microfluidic impedance cytometry devices with an expanded dynamic range and improved enumeration accuracy. This can be exceedingly useful for many biomedical applications, such as infectious disease diagnostics where devices may enumerate larger-scale immune cells alongside sub-micron bacterium in the same sample.

2018 ◽  
Vol 72 (7) ◽  
pp. 1104-1115 ◽  
Author(s):  
Nicholas A. Owens ◽  
Lars B. Laurentius ◽  
Marc D. Porter ◽  
Qun Li ◽  
Sean Wang ◽  
...  

Techniques for the detection of disease biomarkers are key components in the protection of human health. While work over the last few decades has redefined the low-level measurement of disease biomarkers, the translation of these capabilities from the formal clinical setting to point-of-need (PON) usage has been much more limited. This paper presents the results of experiments designed to examine the potential utility of a handheld Raman spectrometer as a PON electronic reader for a sandwich immunoassay based on surface-enhanced Raman scattering (SERS). In so doing, the study herein used a recently developed procedure for the SERS detection of phospho-myo-inositol-capped lipoarabinomannan (PILAM) as a means to compare the performance of laboratory-grade and handheld instrumentation and, therefore, gauge the utility of the handheld instrument for PON deployment. Phospho-myo-inositol-capped lipoarabinomannan is a non-pathogenic simulant for mannose-capped lipoarabinomannan (ManLAM), which is an antigenic marker found in serum and other body fluids of individuals infected with tuberculosis (TB). The results of the measurements with the field-portable spectrometer were then compared to those obtained for the same samples when using a much more sensitive benchtop Raman spectrometer. The results, albeit under different operational settings for the two spectrometers (e.g., signal integration time), are promising in that the limit of detection found for PILAM spiked in human serum when using the handheld system (0.18 ng/mL) approached that of the benchtop instrument (0.032 ng/mL). This work also: (1) identified potential adaptations (e.g., optimization of the plasmonically enhanced response for measurement by the handheld unit through a change in the excitation wavelength) to tighten the gap in performance; and (2) briefly examined the next steps and potential processes required to move this immunoassay platform closer to PON utility.


Author(s):  
A. P. Kovarsky ◽  
V. S. Strykanov

GaN epitaxial films were analyzed by Secondary Ion Mass Spectrometry (SIMS). Standard implanted samples were used to determine the appropriate analytical conditions for analysis of impurities. The dose and energy of implantation for selected elements (Mg, Al, Si, Zn, Cd, H, C and O) were chosen so the maximum impurity concentration was not more than 1020 atoms/cm3. The optimum analysis conditions were ascertained from the standards for each element, and the detection limits were deduced from the background levels of the implantation profiles. We demonstate that lower detection limits of 1015 atoms/cm3 with a dynamic range 103 − 105 are possible. Zn and Cd have low ion yields, so the minimum detection level for these elements is the background level of the detector. The detection limits of the other elements are determined by the contamination of an initial GaN matrix.


Sensors ◽  
2021 ◽  
Vol 21 (6) ◽  
pp. 2117
Author(s):  
Hui Han ◽  
Zhiyuan Ren ◽  
Lin Li ◽  
Zhigang Zhu

Automatic modulation classification (AMC) is playing an increasingly important role in spectrum monitoring and cognitive radio. As communication and electronic technologies develop, the electromagnetic environment becomes increasingly complex. The high background noise level and large dynamic input have become the key problems for AMC. This paper proposes a feature fusion scheme based on deep learning, which attempts to fuse features from different domains of the input signal to obtain a more stable and efficient representation of the signal modulation types. We consider the complementarity among features that can be used to suppress the influence of the background noise interference and large dynamic range of the received (intercepted) signals. Specifically, the time-series signals are transformed into the frequency domain by Fast Fourier transform (FFT) and Welch power spectrum analysis, followed by the convolutional neural network (CNN) and stacked auto-encoder (SAE), respectively, for detailed and stable frequency-domain feature representations. Considering the complementary information in the time domain, the instantaneous amplitude (phase) statistics and higher-order cumulants (HOC) are extracted as the statistical features for fusion. Based on the fused features, a probabilistic neural network (PNN) is designed for automatic modulation classification. The simulation results demonstrate the superior performance of the proposed method. It is worth noting that the classification accuracy can reach 99.8% in the case when signal-to-noise ratio (SNR) is 0 dB.


Biosensors ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 15
Author(s):  
Iulia Rus ◽  
Mihaela Tertiș ◽  
Cristina Barbălată ◽  
Alina Porfire ◽  
Ioan Tomuță ◽  
...  

The aim of this study was to develop a disposable, simple, fast, and sensitive sensor for the simultaneous electrochemical detection of doxorubicin (DOX) and simvastatin (SMV), which could be used in preclinical studies for the development of new pharmaceutical formulations for drug delivery. Firstly, the electrochemical behavior of each molecule was analyzed regarding the influence of electrode material, electrolyte solution, and scan rate. After this, the proper electrode material, electrolyte solution, and scan rate for both active substances were chosen, and a linear sweep voltammetry procedure was optimized for simultaneous detection. Two chronoamperometry procedures were tested, one for the detection of DOX in the presence of SMV, and the other one for the detection of DOX and SMV together. Finally, calibration curves for DOX and SMV in the presence of each other were obtained using both electrochemical methods and the results were compared. The use of amperometry allowed for a better limit of detection (DOX: 0.1 μg/mL; SMV: 0.7 μg/mL) than the one obtained in voltammetry (1.5 μg/mL for both drugs). The limits of quantification using amperometry were 0.5 μg/mL for DOX (dynamic range: 0.5–65 μg/mL) and 2 μg/mL for SMV (dynamic range: 2–65 μg/mL), while using voltammetry 1 μg/mL was obtained for DOX (dynamic range: 1–100 μg/mL) and 5 μg/mL for SMV (dynamic range: 5–100 μg/mL). This detection strategy represents a promising tool for the analysis of new pharmaceutical formulations for targeted drug delivery containing both drugs, whose association was proven to bring benefits in the treatment of cancer.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carlotta Peruzzi ◽  
Silvia Battistoni ◽  
Daniela Montesarchio ◽  
Matteo Cocuzza ◽  
Simone Luigi Marasso ◽  
...  

AbstractIn several biomedical applications, the detection of biomarkers demands high sensitivity, selectivity and easy-to-use devices. Organic electrochemical transistors (OECTs) represent a promising class of devices combining a minimal invasiveness and good signal transduction. However, OECTs lack of intrinsic selectivity that should be implemented by specific approaches to make them well suitable for biomedical applications. Here, we report on a biosensor in which selectivity and a high sensitivity are achieved by interfacing, in an OECT architecture, a novel gate electrode based on aptamers, Au nanoparticles and graphene hierarchically organized to optimize the final response. The fabricated biosensor performs state of the art limit of detection monitoring biomolecules, such as thrombin-with a limit of detection in the picomolar range (≤ 5 pM) and a very good selectivity even in presence of supraphysiological concentrations of Bovine Serum Albumin (BSA-1mM). These accomplishments are the final result of the gate hierarchic structure that reduces sterich indrance that could contrast the recognition events and minimizes false positive, because of the low affinity of graphene towards the physiological environment. Since our approach can be easily applied to a large variety of different biomarkers, we envisage a relevant potential for a large series of different biomedical applications.


2018 ◽  
Vol 27 (07) ◽  
pp. 1850104 ◽  
Author(s):  
Yuwadee Sundarasaradula ◽  
Apinunt Thanachayanont

This paper presents the design and realization of a low-noise, low-power, wide dynamic range CMOS logarithmic amplifier for biomedical applications. The proposed amplifier is based on the true piecewise linear function by using progressive-compression parallel-summation architecture. A DC offset cancellation feedback loop is used to prevent output saturation and deteriorated input sensitivity from inherent DC offset voltages. The proposed logarithmic amplifier was designed and fabricated in a standard 0.18[Formula: see text][Formula: see text]m CMOS technology. The prototype chip includes six limiting amplifier stages and an on-chip bias generator, occupying a die area of 0.027[Formula: see text]mm2. The overall circuit consumes 9.75[Formula: see text][Formula: see text]W from a single 1.5[Formula: see text]V power supply voltage. Measured results showed that the prototype logarithmic amplifier exhibited an 80[Formula: see text]dB input dynamic range (from 10[Formula: see text][Formula: see text]V to 100[Formula: see text]mV), a bandwidth of 4[Formula: see text]Hz–10[Formula: see text]kHz, and a total input-referred noise of 5.52[Formula: see text][Formula: see text]V.


2016 ◽  
Vol 13 (2) ◽  
pp. 458-469
Author(s):  
Baghdad Science Journal

A simple, fast, selective of a new flow injection analysis method coupled with potentiometric detection was used to determine vitamin B1 in pharmaceutical formulations via the prepared new selective membranes. Two electrodes were constructed for the determination of vitamin B1 based on the ion-pair vitamin B1-phosphotungestic acid (B1-PTA) in a poly (vinyl chloride) supported with a plasticized di-butyl phthalate (DBPH) and di-butyl phosphate (DBP). Applications of these ion selective electrodes for the determination of vitamin B1 in the pharmaceutical preparations for batch and flow injection systems were described. The ion selective membrane exhibited a near-Nernstian slope values 56.88 and 58.53 mV / decade, with the linear dynamic range of vitamin B1 was 5 x 10-5- 1 x 10-2 and 1 x 10-4-1 x 10-2 mol.L-1, in batch and FIA, respectively. The limit of detection was 3.5 x 10-5 and 9.5 x 10-5 mol.L-1, with the percentage linearity 98.85 and 95.22 in batch and FIA, respectively. The suggested ion selective electrode has been utilized perfection in the determination of vitamin B1 in pharmaceutical formulations using batch and flow injection system, respectively.


Author(s):  
Totka Dodevska ◽  
Dobrin Hadzhiev ◽  
Ivan Shterev ◽  
Yanna Lazarova

Recently, the development of eco-friendly, cost-effective and reliable methods for synthesis of metal nanoparticles has drawn a considerable attention. The so-called green synthesis, using mild reaction conditions and natural resources as plant extracts and microorganisms, has established as a convenient, sustainable, cheap and environmentally safe approach for synthesis of a wide range of nanomaterials. Over the past decade, biosynthesis is regarded as an important tool for reducing the harmful effects of traditional nanoparticle synthesis methods commonly used in laboratories and industry. This review emphasizes the significance of biosynthesized metal nanoparticles in the field of electrochemical sensing. There is increasing evidence that green synthesis of nanoparticles provides a new direction in designing of cost-effective, highly sensitive and selective electrode-catalysts applicable in food, clinical and environmental analysis. The article is based on 157 references and provided a detailed overview on the main approaches for green synthesis of metal nanoparticles and their applications in designing of electrochemical sensor devices. Important operational characteristics including sensitivity, dynamic range, limit of detection, as well as data on stability and reproducibility of sensors have also been covered. Keywords: biosynthesis; green synthesis; nanomaterials; nanotechnology; modified electrodes


2020 ◽  
Vol 10 (03) ◽  
pp. 395-401
Author(s):  
Mohammad K. Hammood ◽  
Maryam Hamed

Mefenamic acid belongs to non-steroidal anti-inflammatory drugs that are used widely for the treatment of analgesia. Our aim from this study is to establish a new assay for the quantitative determination of mefenamic acid (MFA) in the pharmaceutical sample by two sensitive and rapid flow injection-fluorometric methods. A homemade fluorometer was used in fluorescence measurements, which using solid-state laser diode 405 and 532 nm as a source, combined with a continuous flow injection technique. The first method depends on the effect of MFA on calcein blue (CLB) fluorescence at 405 nm. Another method is a study of rhodamine-6G (Rh-6G) fluorescence after adding MFA, and recording at 532 nm. Optimum parameters as fluorescent dye concentration, basic medium, flow rate, sample volume, purge time, and delay coil have been investigated. The dynamic range of MFA was 0.2 to 2 mmol.L-1; 0.5 to 2.3 mmol.L-1 with linearity percentage (% r2) 98.92 and 99.83%, for Rh-6G and CLB, respectively. Limit of detection at a minimum concentration in calibration curve 189.34 and 199.89 ng/sample, for Rh-6G and CLB, respectively. The comparison of developed methods with the classical method (UV-vis spectrophotometry) was achieved. The proposed methods were successfully applied for the determination of MFA in the pharmaceutical samples and can be used as an alternative method.


1989 ◽  
Vol 43 (3) ◽  
pp. 422-425 ◽  
Author(s):  
Richard T. Madison ◽  
Mary K. Carroll ◽  
Gary M. Hieftje

A sample cell for observing the Shpol'skii effect at 77 K is described and analytically assessed. The cell employs fiber-optic light guides to transport excitation and emission radiation. The system is compact, inexpensive, and simple to construct from commercially available laboratory components, and it alleviates several problems inherent in conventional refrigerated-cell designs. Detection limits for anthracene, coronene, and pyrene obtained with the sample cell are 8.8 × 10−8 M, 8.4 × 10−7 M, and 3.5 × 10−7 M, respectively. The linear dynamic range for each compound is 2 to 3 orders of magnitude.


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