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CMOS cell sensors for point-of-care diagnostics.

Adiguzel Y, Kulah H - Sensors (Basel) (2012)

Bottom Line: The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions.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.

View Article: PubMed Central - PubMed

Affiliation: METU-MEMS Research and Application Center, Middle East Technical University, Ankara 06800, Turkey. yekbun@metu.edu.tr

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 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.

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Schematic drawing of silicone nanowire (SiNW) chip dually functionalized with antibodies against tumor necrosis factor-alpha and interleukin-6, respectively at SiNW-1 and SiNW-2 [93]. S denotes source and D denotes drain. Adapted with the permission of Elsevier.
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f10-sensors-12-10042: Schematic drawing of silicone nanowire (SiNW) chip dually functionalized with antibodies against tumor necrosis factor-alpha and interleukin-6, respectively at SiNW-1 and SiNW-2 [93]. S denotes source and D denotes drain. Adapted with the permission of Elsevier.

Mentions: Reliability and sensitivity are among essential criteria of point-of-care diagnostics. Silicon nanowire-based sensors, which can be fabricated by means of CMOS compatible processes, have the potential to improve sensitivities due to their inherent characteristics. Since, silicon nanowires perform as the conducting channel in proximity to the sensing environment. This is analogous to bulk silicon FETs, where the conducting channel is buried under a dielectric insulating layer [90]. One dimensional structure is further benefited for a large surface-to-volume ratio. Sensitivities, which were revealed to be elevated to a level that was sufficient to detect biomarker proteins down to 1 fg/mL in buffer and 30 fg/mL in undiluted human serum [91], are expected to be effective for cell detection as well. Pui and co-workers [92] utilized silicone nanowire-based FETs to detect adipocytokines secreted by adipocytes, to understand the interplay between the adipocytokines and their physiological functions. Aligned arrays of silicone nanowire single cystals were fabricated by means of top-down CMOS-compatible fabrication techniques [92]. Recently, the same authors [93] employed dually-functionalized silicon nanowire chip (Figure 10) for parallel detection of the secretion of pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6, during immune response of macrophages to the stimulation of bacterial endotoxin lipopolysaccharide. The study was indicated to be not only influential for the study of immunity but key to diagnosis or to monitor drug treatment of pathological states as well [93]. While these approaches may be of use for drug research, a diverse approach came earlier from another study of the same group. They performed electrophysiological measurements at the single-cell level or from tissues, which could be an application in high-throughput drug screening for ion channels [90]. Electrocardiogram (ECG) signals from a beating rat heart was measured by detecting cardioelectricity in characteristic changes of their conducting current, and also, spontaneous membrane action potentials from individual rat cardiomyocytes were transduced into changes in conductance [90]. In the former case, the beating heart was placed into the recording chamber on the top of the nanowire chip; while, in the latter case, the cardiomyocytes were isolated from the hearts of neonatal rats and cultured on the nanowire chip for a few days until the experiment [90]. Another type of muscle cell, rat aortic muscle cells (A7R5) were also sensed with the silicon nanowire chip, for their membrane activities and action potentials, by introducing concentrated potassium solution into the recording chamber [90]. This resulted in the observation of current spikes. The authors stated that the local extracellular voltage at the narrow cleft between the adhering membrane patch and the underneath nanowire was transduced into nanowire current signals, indirectly.


CMOS cell sensors for point-of-care diagnostics.

Adiguzel Y, Kulah H - Sensors (Basel) (2012)

Schematic drawing of silicone nanowire (SiNW) chip dually functionalized with antibodies against tumor necrosis factor-alpha and interleukin-6, respectively at SiNW-1 and SiNW-2 [93]. S denotes source and D denotes drain. Adapted with the permission of Elsevier.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472815&req=5

f10-sensors-12-10042: Schematic drawing of silicone nanowire (SiNW) chip dually functionalized with antibodies against tumor necrosis factor-alpha and interleukin-6, respectively at SiNW-1 and SiNW-2 [93]. S denotes source and D denotes drain. Adapted with the permission of Elsevier.
Mentions: Reliability and sensitivity are among essential criteria of point-of-care diagnostics. Silicon nanowire-based sensors, which can be fabricated by means of CMOS compatible processes, have the potential to improve sensitivities due to their inherent characteristics. Since, silicon nanowires perform as the conducting channel in proximity to the sensing environment. This is analogous to bulk silicon FETs, where the conducting channel is buried under a dielectric insulating layer [90]. One dimensional structure is further benefited for a large surface-to-volume ratio. Sensitivities, which were revealed to be elevated to a level that was sufficient to detect biomarker proteins down to 1 fg/mL in buffer and 30 fg/mL in undiluted human serum [91], are expected to be effective for cell detection as well. Pui and co-workers [92] utilized silicone nanowire-based FETs to detect adipocytokines secreted by adipocytes, to understand the interplay between the adipocytokines and their physiological functions. Aligned arrays of silicone nanowire single cystals were fabricated by means of top-down CMOS-compatible fabrication techniques [92]. Recently, the same authors [93] employed dually-functionalized silicon nanowire chip (Figure 10) for parallel detection of the secretion of pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6, during immune response of macrophages to the stimulation of bacterial endotoxin lipopolysaccharide. The study was indicated to be not only influential for the study of immunity but key to diagnosis or to monitor drug treatment of pathological states as well [93]. While these approaches may be of use for drug research, a diverse approach came earlier from another study of the same group. They performed electrophysiological measurements at the single-cell level or from tissues, which could be an application in high-throughput drug screening for ion channels [90]. Electrocardiogram (ECG) signals from a beating rat heart was measured by detecting cardioelectricity in characteristic changes of their conducting current, and also, spontaneous membrane action potentials from individual rat cardiomyocytes were transduced into changes in conductance [90]. In the former case, the beating heart was placed into the recording chamber on the top of the nanowire chip; while, in the latter case, the cardiomyocytes were isolated from the hearts of neonatal rats and cultured on the nanowire chip for a few days until the experiment [90]. Another type of muscle cell, rat aortic muscle cells (A7R5) were also sensed with the silicon nanowire chip, for their membrane activities and action potentials, by introducing concentrated potassium solution into the recording chamber [90]. This resulted in the observation of current spikes. The authors stated that the local extracellular voltage at the narrow cleft between the adhering membrane patch and the underneath nanowire was transduced into nanowire current signals, indirectly.

Bottom Line: The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions.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.

View Article: PubMed Central - PubMed

Affiliation: METU-MEMS Research and Application Center, Middle East Technical University, Ankara 06800, Turkey. yekbun@metu.edu.tr

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 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.

Show MeSH
Related in: MedlinePlus