scholarly journals Quantitative and rapid Plasmodium falciparum malaria diagnosis and artemisinin-resistance detection using a CMOS Lab-on-Chip platform

2019 ◽  
Author(s):  
K. Malpartida-Cardenas ◽  
N. Miscourides ◽  
J. Rodriguez-Manzano ◽  
L. S. Yu ◽  
J. Baum ◽  
...  

AbstractEarly and accurate diagnosis of malaria and drug-resistance is essential to effective disease management. Available rapid malaria diagnostic tests present limitations in analytical sensitivity, drug-resistant testing and/or quantification. Conversely, diagnostic methods based on nucleic acid amplification stepped forwards owing to their high sensitivity, specificity and robustness. Nevertheless, these methods commonly rely on optical measurements and complex instrumentation which limit their applicability in resource-poor, point-of-care settings. This paper reports the specific, quantitative and fully-electronic detection of Plas-modium falciparum, the predominant malaria-causing parasite worldwide, using a Lab-on-Chip platform developed in-house. Furthermore, we demonstrate on-chip detection of C580Y, the most prevalent single-nucleotide polymorphism associated to artemisinin-resistant malaria. Real-time non-optical DNA sensing is facilitated using Ion-Sensitive Field-Effect Transistors, fabricated in unmodified complementary metal-oxide-semiconductor technology, coupled with loop-mediated isothermal amplification. This work holds significant potential for the development of a fully portable and quantitative malaria diagnostic that can be used as a rapid point-of-care test.

2020 ◽  
Vol 36 (4) ◽  
pp. 112-120
Author(s):  
A.V. Zverev ◽  
M. Andronik ◽  
V.V. Echeistov ◽  
Z.H. Issabayeva ◽  
O.S. Sorokina ◽  
...  

The results of the development and manufacture of an integrated membrane-free sensor for the control of accurate dilution of liquid samples on the microfluidic chip are presented. The proposed type of devices is intended for direct precise measurements of liquid flow rate in microchannels of laboratories-on-chip, including point-of-care systems. The sensor topology was optimized based on the numerical simulation results and technological requirements. The main characteristic of the developed sensor is the lack of a membrane in the design while maintaining the sensitivity and accuracy of the device at the level of a commercial membrane analogue. The fully biocompatible sensor was manufactured using standard microelectronics and soft lithography technologies. In order to optimize the sensor design, 32 different topologies of the device were tested. The integration of the flow sensors on the chip allows to significantly reduce the dead volume of the hydrodynamic system and to control the amount of liquid entering the individual reservoirs of the microfluidic chip. The sensor occupies an area of (210 x 140) um2 in the channel and is characterized by a relative error of 5% in the flow rate range of 100-1000 ul/min. microfluidics, lab-on-chip, calorimetric flow sensor, thermoresistive sensor, numerical simulation, hydrodynamics, complementary metal-oxide-semiconductor, microtechnologies Devices were made at the BMSTU Nanofabrication Facility (FMN Laboratory, FMNS REC, ID 74300).


Biosensors ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 117 ◽  
Author(s):  
Faye M. Walker ◽  
Kuangwen Hsieh

Advances in nucleic acid amplification technologies have revolutionized diagnostics for systemic, inherited, and infectious diseases. Current assays and platforms, however, often require lengthy experimental procedures and multiple instruments to remove contaminants and inhibitors from clinically-relevant, complex samples. This requirement of sample preparation has been a bottleneck for using nucleic acid amplification tests (NAATs) at the point of care (POC), though advances in “lab-on-chip” platforms that integrate sample preparation and NAATs have made great strides in this space. Alternatively, direct NAATs—techniques that minimize or even bypass sample preparation—present promising strategies for developing POC diagnostic tools for analyzing real-world samples. In this review, we discuss the current status of direct NAATs. Specifically, we surveyed potential testing systems published from 1989 to 2017, and analyzed their performances in terms of robustness, sensitivity, clinical relevance, and suitability for POC diagnostics. We introduce bubble plots to facilitate our analysis, as bubble plots enable effective visualization of the performances of these direct NAATs. Through our review, we hope to initiate an in-depth examination of direct NAATs and their potential for realizing POC diagnostics, and ultimately transformative technologies that can further enhance healthcare.


Micromachines ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 544 ◽  
Author(s):  
Ganesh Jayakumar ◽  
Per-Erik Hellström ◽  
Mikael Östling

Silicon ribbons (SiRi) have been well-established as highly sensitive transducers for biosensing applications thanks to their high surface to volume ratio. However, selective and multiplexed detection of biomarkers remains a challenge. Further, very few attempts have been made to integrate SiRi with complementary-metal-oxide-semiconductor (CMOS) circuits to form a complete lab-on-chip (LOC). Integration of SiRi with CMOS will facilitate real time detection of the output signal and provide a compact small sized LOC. Here, we propose a novel pixel based SiRi device monolithically integrated with CMOS field-effect-transistors (FET) for real-time selective multiplexed detection. The SiRi pixels are fabricated on a silicon-on-insulator wafer using a top-down method. Each pixel houses a control FET, fluid-gate (FG) and SiRi sensor. The pixel is controlled by simultaneously applying frontgate (VG) and backgate voltage (VBG). The liquid potential can be monitored using the FG. We report the transfer characteristics (ID-VG) of N- and P-type SiRi pixels. Further, the ID-VG characteristics of the SiRis are studied at different VBG. The application of VBG to turn ON the SiRi modulates the subthreshold slope (SS) and threshold voltage (VTH) of the control FET. Particularly, N-type pixels cannot be turned OFF due to the control NFET operating in the strong inversion regime. This is due to large VBG (≥25 V) application to turn ON the SiRi sensor. Conversely, the P-type SiRi sensors do not require large VBG to switch ON. Thus, P-type pixels exhibit excellent ION/IOFF ≥ 106, SS of 70–80 mV/dec and VTH of 0.5 V. These promising results will empower the large-scale cost-efficient production of SiRi based LOC sensors.


2008 ◽  
Vol 94 (2) ◽  
pp. 216-225 ◽  
Author(s):  
Marco Bianchessi ◽  
Sarah Burgarella ◽  
Marco Cereda

The development of new powerful applications and the improvement in fabrication techniques are promising an explosive growth in lab-on-chip use in the upcoming future. As the demand reaches significant levels, the semiconductor industry may enter in the field, bringing its capability to produce complex devices in large volumes, high quality and low cost. The lab-on-chip concept, when applied to medicine, leads to the point-of-care concept, where simple, compact and cheap instruments allow diagnostic assays to be performed quickly by untrained personnel directly at the patient's side. In this paper, some practical and economical considerations are made to support the advantages of point-of-care testing. A series of promising technologies developed by STMicroelectronics on lab-on-chips is also presented, mature enough to enter in the common medical practice. The possible use of these techniques for cancer research, diagnosis and treatment are illustrated together with the benefits offered by their implementation in point-of-care testing.


2015 ◽  
Vol 451 ◽  
pp. 240-246 ◽  
Author(s):  
Nicola Marziliano ◽  
Maria Francesca Notarangelo ◽  
Marco Cereda ◽  
Vittoria Caporale ◽  
Lucia Coppini ◽  
...  
Keyword(s):  

2021 ◽  
Vol 8 (3) ◽  
pp. 031313
Author(s):  
Aref Asghari ◽  
Chao Wang ◽  
Kyoung Min Yoo ◽  
Ali Rostamian ◽  
Xiaochuan Xu ◽  
...  

2020 ◽  
Vol 4 (9) ◽  
Author(s):  
Solihah Maketar ◽  
Nurhidanatasha Abu Bakar

Massive elimination efforts have been done to control the malaria disease caused by the emergence of the fifth human malaria parasite known as Plasmodium knowlesi. Early detection of the parasite is important in treating malaria infection. Microscopic examination of Giemsa-stained thick and thin blood films is the gold standard for laboratory malaria diagnosis, while rapid diagnostic tests (RDTs), polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) are significant diagnostic techniques to detect acute infection. However, these methods have several limitations in which it could delay the treatment. The potential of lab-on-chip (LOC) as a point-of-care diagnostic tool for malaria fulfils the requirement of limitations where it is able to produce early detection of malaria infection. This review discusses advantages and disadvantages of malaria diagnostic methods as well as new approaches that could be used for high speed, sensitive and reliable malaria detection to prevent the disease from causing severe complications and even fatal if left untreated.


Micromachines ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1003
Author(s):  
Saghi Forouhi ◽  
Ebrahim Ghafar-Zadeh

Emerging infectious diseases such as coronavirus disease of 2019 (COVID-19), Ebola, influenza A, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) in recent years have threatened the health and security of the global community as one of the greatest factors of mortality in the world. Accurate and immediate diagnosis of infectious agents and symptoms is a key to control the outbreak of these diseases. Rapid advances in complementary metal-oxide-semiconductor (CMOS) technology offers great advantages like high accuracy, high throughput and rapid measurements in biomedical research and disease diagnosis. These features as well as low cost, low power and scalability of CMOS technology can pave the way for the development of powerful devices such as point-of-care (PoC) systems, lab-on-chip (LoC) platforms and symptom screening devices for accurate and timely diagnosis of infectious diseases. This paper is an overview of different CMOS-based devices such as optical, electrochemical, magnetic and mechanical sensors developed by researchers to mitigate the problems associated with these diseases.


Sensors ◽  
2019 ◽  
Vol 19 (8) ◽  
pp. 1917 ◽  
Author(s):  
Shane O’Sullivan ◽  
Zulfiqur Ali ◽  
Xiaoyi Jiang ◽  
Reza Abdolvand ◽  
M Selim Ünlü ◽  
...  

We review some emerging trends in transduction, connectivity and data analytics for Point-of-Care Testing (POCT) of infectious and non-communicable diseases. The patient need for POCT is described along with developments in portable diagnostics, specifically in respect of Lab-on-chip and microfluidic systems. We describe some novel electrochemical and photonic systems and the use of mobile phones in terms of hardware components and device connectivity for POCT. Developments in data analytics that are applicable for POCT are described with an overview of data structures and recent AI/Machine learning trends. The most important methodologies of machine learning, including deep learning methods, are summarised. The potential value of trends within POCT systems for clinical diagnostics within Lower Middle Income Countries (LMICs) and the Least Developed Countries (LDCs) are highlighted.


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