A microfluidic device integrating dual CMOS polysilicon nanowire sensors for on-chip whole blood processing and simultaneous detection of multiple analytes

Kuan, Da-Han; Wang, I-Shun; Lin, Jiun-Rue; Yang, Congrong; Huang, Chi-Hsien; Lin, Yen‐Hung; Lin, Chih‐Ting; Huang, Nien-Tsu

doi:10.1039/c6lc00410e

Cited by 38 publications

(23 citation statements)

References 32 publications

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“…We then used a spectrophotometer (Nanodrop One, Thermo Fisher Scientific Inc., MA) to measure the 280-nm absorbance intensity of each dilution factor, which correlates to the total protein concentration due to three amino acids (tryptophan, phenylalanine, and tyrosine) 34 . The protein concentration and composition may vary between different clinical samples, so standard curves of each sample were constructed individually (Supplementary Fig S2 ).…”

Section: Resultsmentioning

confidence: 99%

A Microfluidic Device for Simultaneous Extraction of Plasma, Red Blood Cells, and On-Chip White Blood Cell Trapping

Kuan

et al. 2018

Sci Rep

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This study reports a microfluidic device for whole blood processing. The device uses the bifurcation law, cross-flow method, and hydrodynamic flow for simultaneous extraction of plasma, red blood cells, and on-chip white blood cell trapping. The results demonstrate successful plasma and red blood cell collection with a minimum dilution factor (0.76x) and low haemolysis effect. The extracted red blood cells can also be applied for blood type tests. Moreover, the device can trap up to ~1,800 white blood cells in 20 minutes. The three components can be collected simultaneously using only 6 μL of whole blood without any sample preparation processes. Based on these features, the microfluidic device enables low-cost, rapid, and efficient whole blood processing functionality that could potentially be applied for blood analysis in resource-limited environments or point-of-care settings.

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Section: Resultsmentioning

confidence: 99%

A Microfluidic Device for Simultaneous Extraction of Plasma, Red Blood Cells, and On-Chip White Blood Cell Trapping

Kuan

et al. 2018

Sci Rep

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“…Vortex flow is induced in the microchannels of a micromachined polymethyl‐methacrylate based microfluidic device to achieve uniform sample dilution. The CMOS polysilicon nanowires are interfaced with a picoammeter to form a label‐free dynamic detection scheme without needing to contain the particles in a chamber . CMOS further enables us to integrate sensors in extremely small‐sized areas, which can easily beat the sensitivity and performance of commercially available sensors.…”

Section: Role Of Cmos In Microfluidicsmentioning

confidence: 99%

“…These DEP forces are generated by providing sinusoidal voltages to the metal electrodes through CMOS transfer gates . Kuan et al shaped an automatic real‐time fluidic control in a blood processing device using programmable microfabricated piezoelectric pumps that mixed blood sample with phosphate‐buffered saline . Chen et al and Gao et al have shown the dual use of a microheater array of microfabricated capacitive electrodes to also act as thermocapillary droplet‐propulsion actuators .…”

Section: Role Of Cmos In Microfluidicsmentioning

confidence: 99%

“…Technology has now advanced so much that there are fully integrated sample‐in‐results‐out chips for genetic analysis, sensors that can detect a handful of molecules, and many other similar systems . Complementary metal oxide semiconductor (CMOS) integrated LOC systems can be developed using CMOS technologies as sensors, signal conditioners, data processing circuitry, actuators, and wireless communication capabilities . CMOS is a set of microfabrication and nanofabrication processes, which is used to manufacture semiconductor chips present inside computer, smartphone, or any electronic gadgets.…”

Section: Introductionmentioning

confidence: 99%

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CMOS Enabled Microfluidic Systems for Healthcare Based Applications

et al. 2018

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additional parts, such as syringe pumps, control valves, and microscopes, which not only increase the complexity and cost of the system but also create a dependence of the system on a laboratorybased environment. Technology has now advanced so much that there are fully integrated sample-in-results-out chips for genetic analysis, [8] sensors that can detect a handful of molecules, and many other similar systems. [9] Complementary metal oxide semiconductor (CMOS) integrated LOC systems can be developed using CMOS technologies as sensors, signal conditioners, data processing circuitry, actuators, and wireless communication capabilities. [10][11][12][13][14][15][16][17] CMOS is a set of microfabrication and nanofabrication processes, which is used to manufacture semiconductor chips present inside computer, smartphone, or any electronic gadgets. Consequently, these chips are referred to as CMOS enabled or CMOS based chips. CMOS based chips can act as a processor, memory, and digital logic circuitry for data management. In this review, we will discuss how CMOS based devices have enabled both management of data from microfluidic devices as well as sensors and actuators to help complement the functionality of LOC devices. CMOS logics are simple to make, and consume little to no current in idle state. With the advancements in Moore's law we have seen the size of CMOS devices getting smaller and smaller allowing for more functionality to fit in a smaller area. [18] CMOS plays a significant role in the realization of portable and versatile microfluidic platforms by integrating them with microscale sensors, interfaces, and actuators to form autonomous hybrid systems. [10,12,16] Adding interface electronics to the same CMOS chip as sensors, actuators, data processing, and communication capabilities creates a universal platform for LOC technologies. Having signal amplification and noise removal right at the sensor interface without any signal loss makes the device output more accurate and sensitive, and also removes parasitic and mismatch errors. [1] By using CMOScompatible processes, it is possible to interface directly with the readout circuitry to form an integrated circuit system on a single chip. Signal acquisition from a large array of sensors to a single system requires a complex integration scheme, but CMOS microfabrication processes enable the integration of analogue multiplexers with biosensors on small dice. [19] CMOS also has the capability to actuate pumps and valves in microfluidic devices or to directly influence the fluid itself using electric With the increased global population, it is more important than ever to expand accessibility to affordable personalized healthcare. In this context, a seamless integration of microfluidic technology for bioanalysis and drug delivery and complementary metal oxide semiconductor (CMOS) technology enabled data-management circuitry is critical. Therefore, here, the fundamentals, integration aspects, and applications of CMOS-enabled microfluidic systems for affordable persona...

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“…To pave the way toward POC diagnosis for cardiac disease, in this work, CMOS field-effect biosensing technology is employed for cardiac disease diagnosis with multiple biomarkers in serum. Compared with another CMOS-compatible micro-cantilever biosensing technology, CMOS field-effect biosensing technology has advantages of fabrication and integration with interface circuits and microfluidity [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Pre-Clinical Tests of an Integrated CMOS Biomolecular Sensor for Cardiac Diseases Diagnosis

Lee

Wang

Huang

et al. 2017

Sensors

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Coronary artery disease and its related complications pose great threats to human health. In this work, we aim to clinically evaluate a CMOS field-effect biomolecular sensor for cardiac biomarkers, cardiac-specific troponin-I (cTnI), N-terminal prohormone brain natriuretic peptide (NT-proBNP), and interleukin-6 (IL-6). The CMOS biosensor is implemented via a standard commercialized 0.35 μm CMOS process. To validate the sensing characteristics, in buffer conditions, the developed CMOS biosensor has identified the detection limits of IL-6, cTnI, and NT-proBNP as being 45 pM, 32 pM, and 32 pM, respectively. In clinical serum conditions, furthermore, the developed CMOS biosensor performs a good correlation with an enzyme-linked immuno-sorbent assay (ELISA) obtained from a hospital central laboratory. Based on this work, the CMOS field-effect biosensor poses good potential for accomplishing the needs of a point-of-care testing (POCT) system for heart disease diagnosis.

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A microfluidic device integrating dual CMOS polysilicon nanowire sensors for on-chip whole blood processing and simultaneous detection of multiple analytes

Cited by 38 publications

References 32 publications

A Microfluidic Device for Simultaneous Extraction of Plasma, Red Blood Cells, and On-Chip White Blood Cell Trapping

A Microfluidic Device for Simultaneous Extraction of Plasma, Red Blood Cells, and On-Chip White Blood Cell Trapping

CMOS Enabled Microfluidic Systems for Healthcare Based Applications

Pre-Clinical Tests of an Integrated CMOS Biomolecular Sensor for Cardiac Diseases Diagnosis

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