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Special Issue "Micro and Nano Technologies for Point-of-Care Diagnosis"

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A special issue of Sensors (ISSN 1424-8220).

Deadline for manuscript submissions: closed (15 May 2012)

Special Issue Editors

Guest Editor
Dr. Utkan Demirci

Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Website | E-Mail
Interests: bioMEMS; bioprinting; global health; tissue engineering; microfluidics for cryopreservation
Guest Editor
Dr. Haluk Külah

Department of Electrical and Electronics Engineering, MEMS Research and Applications Center Middle East Technical University, 06531 Ankara, Turkey
Website | E-Mail
Interests: micro/nano electromechanical systems (MEMS); bioMEMS, MEMS based biosensors; energy scavenging and micro power generation; wireless integrated microsystems; interface electronics design for nano/micro scale sensors and actuators

Special Issue Information

Dear Colleagues,

Since the first introduction in 1970’s, MEMS technology is becoming popular in many different application areas, including military, automotive, and consumer electronics, as it provides cheap, small, and smart sensors and actuators.  Being an enabling technology, MEMS is especially critical for biomedical applications, resulting in a new research area shortly called BioMEMS.  Application areas of BioMEMS range from diagnostics to micro-fluidics, systems for drug delivery, tissue engineering, and implantable biomedical systems.  One of the most interesting application areas for this technology is the point-of-care diagnosis (POC) systems, where MEMS can provide miniaturized devices with simple sample processing, reduced cost of operation, ease of use minimizing the need for skilled operators, portability, and short test turn-around time.  These technologies have potential to enable novel real time monitoring systems by incorporating these systems with wireless electronics and implanting them inside the body for various applications including real time measurement of blood for early diagnosis of diseases such as cancer, and HIV. Further, it is possible to store drugs and release them to the body according to the analysis results, enabling treatment besides diagnosis in the near future.  With these advancements in the field, this special issue of the Sensors Journal will cover the advances in biomedical microsystems in the scope of point-of-care diagnosis, and will focus to grasp the latest trends.

Dr. Utkan Demirci
Dr. Haluk Külah
Guest Editors

Keywords

  • point-of-care diagnosis
  • microsystems
  • MEMS
  • lab-on-a-chip
  • micro total analysis systems (µTAS)

Published Papers (7 papers)

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Research

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Open AccessArticle Numerical and Experimental Study on the Development of Electric Sensor as for Measurement of Red Blood Cell Deformability in Microchannels
Sensors 2012, 12(8), 10566-10583; doi:10.3390/s120810566
Received: 10 May 2012 / Revised: 18 July 2012 / Accepted: 25 July 2012 / Published: 3 August 2012
PDF Full-text (748 KB) | HTML Full-text | XML Full-text
Abstract
A microsensor that can continuously measure the deformability of a single red blood cell (RBC) in its microchannels using microelectrodes is described in this paper. The time series of the electric resistance is measured using an AC current vs. voltage method as the
[...] Read more.
A microsensor that can continuously measure the deformability of a single red blood cell (RBC) in its microchannels using microelectrodes is described in this paper. The time series of the electric resistance is measured using an AC current vs. voltage method as the RBC passes between counter-electrode-type micro-membrane sensors attached to the bottom wall of the microchannel. The RBC is deformed by the shear flow created in the microchannel; the degree of deformation depends on the elastic modulus of the RBC. The resistance distribution, which is unique to the shape of the RBC, is analyzed to obtain the deformability of each cell. First, a numerical simulation of the electric field around the electrodes and RBC is carried out to evaluate the influences of the RBC height position, channel height, distance between the electrodes, electrode width, and RBC shape on the sensor sensitivity. Then, a microsensor was designed and fabricated on the basis of the numerical results. Resistance measurement was carried out using samples of normal RBCs and rigidified (Ca2+-A23186 treated) RBCs. Visualization measurement of the cells’ behavior was carried out using a high-speed camera, and the results were compared with those obtained above to evaluate the performance of the sensor. Full article
(This article belongs to the Special Issue Micro and Nano Technologies for Point-of-Care Diagnosis)
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Open AccessArticle Multiplex Immunoassay Platforms Based on Shape-Coded Poly(ethylene glycol) Hydrogel Microparticles Incorporating Acrylic Acid
Sensors 2012, 12(6), 8426-8436; doi:10.3390/s120608426
Received: 3 May 2012 / Revised: 25 May 2012 / Accepted: 5 June 2012 / Published: 20 June 2012
Cited by 9 | PDF Full-text (621 KB) | HTML Full-text | XML Full-text
Abstract
A suspension protein microarray was developed using shape-coded poly(ethylene glycol) (PEG) hydrogel microparticles for potential applications in multiplex and high-throughput immunoassays. A simple photopatterning process produced various shapes of hydrogel micropatterns that were weakly bound to poly(dimethylsiloxane) (PDMS)-coated substrates. These micropatterns were easily
[...] Read more.
A suspension protein microarray was developed using shape-coded poly(ethylene glycol) (PEG) hydrogel microparticles for potential applications in multiplex and high-throughput immunoassays. A simple photopatterning process produced various shapes of hydrogel micropatterns that were weakly bound to poly(dimethylsiloxane) (PDMS)-coated substrates. These micropatterns were easily detached from substrates during the washing process and were collected as non-spherical microparticles. Acrylic acids were incorporated into hydrogels, which could covalently immobilize proteins onto their surfaces due to the presence of carboxyl groups. The amount of immobilized protein increased with the amount of acrylic acid due to more available carboxyl groups. Saturation was reached at 25% v/v of acrylic acid. Immunoassays with IgG and IgM immobilized onto hydrogel microparticles were successfully performed with a linear concentration range from 0 to 500 ng/mL of anti-IgG and anti-IgM, respectively. Finally, a mixture of two different shapes of hydrogel microparticles immobilizing IgG (circle) and IgM (square) was prepared and it was demonstrated that simultaneous detection of two different target proteins was possible without cross-talk using same fluorescence indicator because each immunoassay was easily identified by the shapes of hydrogel microparticles. Full article
(This article belongs to the Special Issue Micro and Nano Technologies for Point-of-Care Diagnosis)

Review

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Open AccessReview Development of a Novel, Fully-Automated Genotyping System: Principle and Applications
Sensors 2012, 12(12), 16614-16627; doi:10.3390/s121216614
Received: 15 May 2012 / Revised: 2 October 2012 / Accepted: 26 November 2012 / Published: 3 December 2012
Cited by 8 | PDF Full-text (611 KB) | HTML Full-text | XML Full-text
Abstract
Genetic testing prior to treatment, pharmacogenetic analysis, is key to realizing personalized medicine which is a topic that has attracted much attention recently. Through the optimization of therapy selection and dosage, a reduction in side effects is expected. Genetic testing has been conducted
[...] Read more.
Genetic testing prior to treatment, pharmacogenetic analysis, is key to realizing personalized medicine which is a topic that has attracted much attention recently. Through the optimization of therapy selection and dosage, a reduction in side effects is expected. Genetic testing has been conducted as a type of pharmacogenetic analysis in recent years, but it faces challenges in terms of cost effectiveness and its complicated procedures. Here we report on the development of a novel platform for genetic testing, the i-densyTM, with the use of quenching probe system (QP-system) as principle of mutant detection. The i-densyTM automatically performs pre-treatment, PCR and detection to provide the test result from whole blood and extracted DNA within approximately 90 and 60 min, respectively. Integration of all steps into a single platform greatly reduces test time and complicated procedures. An even higher-precision genetic analysis has been achieved through the development of novel and highly-specific detection methods. The applications of items measured using the i-densyTM are diverse, from single nucleotide polymorphism (SNP), such as CYP2C19 and UGT1A1, to somatic mutations associated with cancer, such as EGFR, KRAS and JAK2. The i-densyTM is a useful tool for optimization of anticancer drug therapy and can contribute to personalized medicine. Full article
(This article belongs to the Special Issue Micro and Nano Technologies for Point-of-Care Diagnosis)
Open AccessReview Porous Bead-Based Diagnostic Platforms: Bridging the Gaps in Healthcare
Sensors 2012, 12(11), 15467-15499; doi:10.3390/s121115467
Received: 1 September 2012 / Revised: 25 October 2012 / Accepted: 1 November 2012 / Published: 9 November 2012
Cited by 14 | PDF Full-text (4379 KB) | HTML Full-text | XML Full-text
Abstract
Advances in lab-on-a-chip systems have strong potential for multiplexed detection of a wide range of analytes with reduced sample and reagent volume; lower costs and shorter analysis times. The completion of high-fidelity multiplexed and multiclass assays remains a challenge for the medical microdevice
[...] Read more.
Advances in lab-on-a-chip systems have strong potential for multiplexed detection of a wide range of analytes with reduced sample and reagent volume; lower costs and shorter analysis times. The completion of high-fidelity multiplexed and multiclass assays remains a challenge for the medical microdevice field; as it struggles to achieve and expand upon at the point-of-care the quality of results that are achieved now routinely in remote laboratory settings. This review article serves to explore for the first time the key intersection of multiplexed bead-based detection systems with integrated microfluidic structures alongside porous capture elements together with biomarker validation studies. These strategically important elements are evaluated here in the context of platform generation as suitable for near-patient testing. Essential issues related to the scalability of these modular sensor ensembles are explored as are attempts to move such multiplexed and multiclass platforms into large-scale clinical trials. Recent efforts in these bead sensors have shown advantages over planar microarrays in terms of their capacity to generate multiplexed test results with shorter analysis times. Through high surface-to-volume ratios and encoding capabilities; porous bead-based ensembles; when combined with microfluidic elements; allow for high-throughput testing for enzymatic assays; general chemistries; protein; antibody and oligonucleotide applications. Full article
(This article belongs to the Special Issue Micro and Nano Technologies for Point-of-Care Diagnosis)
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Open AccessReview Lab-on-a-Chip Pathogen Sensors for Food Safety
Sensors 2012, 12(8), 10713-10741; doi:10.3390/s120810713
Received: 9 May 2012 / Revised: 28 June 2012 / Accepted: 4 July 2012 / Published: 6 August 2012
Cited by 48 | PDF Full-text (1224 KB) | HTML Full-text | XML Full-text
Abstract
There have been a number of cases of foodborne illness among humans that are caused by pathogens such as Escherichia coli O157:H7, Salmonella typhimurium, etc. The current practices to detect such pathogenic agents are cell culturing, immunoassays, or polymerase chain reactions
[...] Read more.
There have been a number of cases of foodborne illness among humans that are caused by pathogens such as Escherichia coli O157:H7, Salmonella typhimurium, etc. The current practices to detect such pathogenic agents are cell culturing, immunoassays, or polymerase chain reactions (PCRs). These methods are essentially laboratory-based methods that are not at all real-time and thus unavailable for early-monitoring of such pathogens. They are also very difficult to implement in the field. Lab-on-a-chip biosensors, however, have a strong potential to be used in the field since they can be miniaturized and automated; they are also potentially fast and very sensitive. These lab-on-a-chip biosensors can detect pathogens in farms, packaging/processing facilities, delivery/distribution systems, and at the consumer level. There are still several issues to be resolved before applying these lab-on-a-chip sensors to field applications, including the pre-treatment of a sample, proper storage of reagents, full integration into a battery-powered system, and demonstration of very high sensitivity, which are addressed in this review article. Several different types of lab-on-a-chip biosensors, including immunoassay- and PCR-based, have been developed and tested for detecting foodborne pathogens. Their assay performance, including detection limit and assay time, are also summarized. Finally, the use of optical fibers or optical waveguide is discussed as a means to improve the portability and sensitivity of lab-on-a-chip pathogen sensors. Full article
(This article belongs to the Special Issue Micro and Nano Technologies for Point-of-Care Diagnosis)
Open AccessReview CMOS Cell Sensors for Point-of-Care Diagnostics
Sensors 2012, 12(8), 10042-10066; doi:10.3390/s120810042
Received: 15 May 2012 / Revised: 6 July 2012 / Accepted: 21 July 2012 / Published: 25 July 2012
Cited by 9 | PDF Full-text (2336 KB) | HTML Full-text | XML Full-text
Abstract
The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions. From this perspective, point-of-care diagnostics is a demanded field in clinics. It is also necessary both for prompt diagnosis and
[...] Read more.
The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions. From this perspective, point-of-care diagnostics is a demanded field in clinics. It is also necessary both for prompt diagnosis and for providing health services evenly throughout the population, including the rural districts. The requirements can only be fulfilled by technologies whose productivity has already been proven, such as complementary metal-oxide-semiconductors (CMOS). CMOS-based products can enable clinical tests in a fast, simple, safe, and reliable manner, with improved sensitivities. Portability due to diminished sensor dimensions and compactness of the test set-ups, along with low sample and power consumption, is another vital feature. CMOS-based sensors for cell studies have the potential to become essential counterparts of point-of-care diagnostics technologies. Hence, this review attempts to inform on the sensors fabricated with CMOS technology for point-of-care diagnostic studies, with a focus on CMOS image sensors and capacitance sensors for cell studies. Full article
(This article belongs to the Special Issue Micro and Nano Technologies for Point-of-Care Diagnosis)
Open AccessReview Screening of Aptamers on Microfluidic Systems for Clinical Applications
Sensors 2012, 12(7), 9514-9529; doi:10.3390/s120709514
Received: 30 May 2012 / Revised: 2 July 2012 / Accepted: 6 July 2012 / Published: 11 July 2012
Cited by 19 | PDF Full-text (501 KB) | HTML Full-text | XML Full-text
Abstract
The use of microfluidic systems for screening of aptamers and their biomedical applications are reviewed in this paper. Aptamers with different nucleic acid sequences have been extensively studied and the results demonstrated a strong binding affinity to target molecules such that they can
[...] Read more.
The use of microfluidic systems for screening of aptamers and their biomedical applications are reviewed in this paper. Aptamers with different nucleic acid sequences have been extensively studied and the results demonstrated a strong binding affinity to target molecules such that they can be used as promising candidate biomarkers for diagnosis and therapeutics. Recently, the aptamer screening protocol has been conducted with microfluidic-based devices. Furthermore, aptamer affinity screening by a microfluidic-based method has demonstrated remarkable advantages over competing traditional methods. In this paper, we first reviewed microfluidic systems which demonstrated efficient and rapid screening of a specific aptamer. Then, the clinical applications of screened aptamers, also performed by microfluidic systems, are further reviewed. These automated microfluidic systems can provide advantages over their conventional counterparts including more compactness, faster analysis, less sample/reagent consumption and automation. An aptamer-based compact microfluidic system for diagnosis may even lead to a point-of-care device. The use of microfluidic systems for aptamer screening and diagnosis is expected to continue growing in the near future and may make a substantial impact on biomedical applications. Full article
(This article belongs to the Special Issue Micro and Nano Technologies for Point-of-Care Diagnosis)

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