ISFETs in CMOS and Emergent Trends in Instrumentation: A Review

Moser, Nicolas; Lande, Tor Sverre; Toumazou, C.; Georgiou, Pantelis

doi:10.1109/jsen.2016.2585920

Cited by 207 publications

(154 citation statements)

References 79 publications

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“…Electrochemical sensing for the detection of the pH changes induced during pH-LAMP is facilitated using ISFETs fabricated in unmodified complementary metal-oxide-semiconductor (CMOS) technology. ISFETs detect changes in the concentration of hydrogen ions at the passivation layer of the microchip through the modulation of an induced voltage across that layer 22,39 . This way, owing to the compatibility of fabrication in standard CMOS technology allows for the mass manufacturing, low cost, and miniaturisation of sensors while ensuring non-optical and fully-electronic chemical (pH) detection.…”

Section: Snv-specific Lamp On a Microchip-based Lab-on-chip Platformmentioning

confidence: 99%

A novel hotspot specific isothermal amplification method for detection of the common PIK3CA p.H1047R breast cancer mutation

Kalofonou

Malpartida-Cardenas

Alexandrou

et al. 2020

Sci Rep

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Breast cancer (BC) is a common cancer in women worldwide. Despite advances in treatment, up to 30% of women eventually relapse and die of metastatic breast cancer. Liquid biopsy analysis of circulating cell-free DNA fragments in the patients' blood can monitor clonality and evolving mutations as a surrogate for tumour biopsy. Next generation sequencing platforms and digital droplet PCR can be used to profile circulating tumour DNA from liquid biopsies; however, they are expensive and time consuming for clinical use. Here, we report a novel strategy with proof-of-concept data that supports the usage of loop-mediated isothermal amplification (LAMP) to detect PIK3CA c.3140 A > G (H1047R), a prevalent BC missense mutation that is attributed to BC tumour growth. Allele-specific primers were designed and optimized to detect the p.H1047R variant following the USS-sbLAMP method. The assay was developed with synthetic DNA templates and validated with DNA from two breast cancer cell-lines and two patient tumour tissue samples through a qPCR instrument and finally piloted on an ISFET enabled microchip. This work sets a foundation for BC mutational profiling on a Lab-on-Chip device, to help the early detection of patient relapse and to monitor efficacy of systemic therapies for personalised cancer patient management.Breast cancer (BC) has a lifetime incidence risk of 12%, with an overall survival of more than 70% of reported cases when early detection is possible 1,2 . Although surgery is capable of removing the primary tumour, minimal residual disease (MRD)/micrometastases may persist resulting in eventual resistance to therapy and recurrence 3 . MRD can often persist even after adjuvant therapy and can grow and spread overtime, remaining undetectable through mammograms, MRI scans and current tumour marker blood tests, such as CA-15-3 and CA 27.29 antigen assays 4 . These current tumour marker blood tests work as a cost-effective method to measure disease progression but do not provide information about mutational changes and heterogeneity of the primary tumour or MRD. With the development of new, non-cross-resistant treatments for breast cancer, early detection of MRD/micrometastases and mutational profiling of circulating tumour DNA (ctDNA) provides an attractive, cost-effective alternative approach to the detection of early signs of relapse and treatment switching.Previous research has proven that circulating free DNA (cfDNA) contains DNA fragments from cancer cells (ctDNA) that are released in blood, showing somatic mutations that reflect the original cancer and evolved clonal subtypes 5 . In particular, recent efforts have established that hotspot mutations in PIK3CA, a gene mutated in 20-40% of metastatic BC, are also commonly observed in screen-detected stage-1 BCs 6 . The PI3K protein is involved in the AKT/mTOR pathway and, when deregulated, leads to tumour-cell growth 7 . Investigation has

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Section: Snv-specific Lamp On a Microchip-based Lab-on-chip Platformmentioning

confidence: 99%

A novel hotspot specific isothermal amplification method for detection of the common PIK3CA p.H1047R breast cancer mutation

Kalofonou

Malpartida-Cardenas

Alexandrou

et al. 2020

Sci Rep

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“…These results indicate that the external strain could be used as stimuli to modulate the channel current and in this regard the presented FET could also be used as a strain sensor. The modulation of device channel current by external stimuli such as touch/contact force, temperature and even chemicals has been used in past to obtain highly sensitive physical and chemical sensors [4], [31]- [35]. Further, we have studied the impact of the strain on the performance of the TFET based 10 stage inverter chain ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Monolayer MoSe₂-Based Tunneling Field Effect Transistor for Ultrasensitive Strain Sensing

Dubey

Yogeswaran

Liu

et al. 2020

IEEE Trans. Electron Devices

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2020) Monolayer MoSe₂-based tunneling field effect transistor for ultrasensitive strain sensing. IEEE Transactions on Electron Devices, (Abstract-This paper presents a detailed investigation of the impact of mechanical strain on transition metal dichalcogenide (TMD) material based tunneling field-effect transistor (TFET). First, the impact of mechanical strain on material parameters of MoSe2 is calculated using the first principle of density functional theory (DFT) under meta generalized gradient approximation (MGGA). The device performance of the TMD TFET has been studied by solving the self-consistent 3D Poisson and Schrodinger equations in non-equilibrium Green's function (NEGF) framework. The results demonstrate that both ION and IOFF increase with uniaxial tensile strain, however, the change in ION/IOFF ratio remains small. This strain dependent performance change in TMD TFET has been utilized to design an ultra-sensitive strain sensor. The device shows a sensitivity (ΔIDS/IDS) of 3.61 for a strain of 2%. Due to the high sensitivity to the strain, these result shows the potential of using MoSe2 TFET as a flexible strain sensor. Furthermore, the strained TFET is analyzed for backend circuit performance. It is observed that the speed and energy efficiency of 10 stage inverter chain based on controlled strain improve substantially in comparison to unstrained TFET.Index Terms-TMD TFET, transition metal dichalcogenides, uniaxial strain.

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“…However this comes at the cost of non-linear characteristics, such as offset and drift, due to the intrinsic passivation layer as sensing membrane and the floating gate structure [8]. Therefore various ISFET readout circuits have been proposed to accommodate or minimize nonideal effects whilst maintaining a low power budget in a largescale system [16].…”

Section: Overview Of Isfet Readout Circuitsmentioning

confidence: 99%

“…4. The drift and low frequency noise limits of the sensor can be defined according to [8], [9], [13], [16]. It can be found the noise contribution from minimum transistors of this technology is much smaller than the drift rate reported.…”

Section: B Sensor Pixel and Arraymentioning

confidence: 99%

Ultrafast Large-Scale Chemical Sensing With CMOS ISFETs: A Level-Crossing Time-Domain Approach

Liu

Constandinou

Georgiou

2019

IEEE Trans. Biomed. Circuits Syst.

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The introduction of large-scale chemical sensing systems in CMOS which integrate millions of ISFET sensors have allowed applications such as DNA sequencing and fine-pixel chemical imaging systems to be realised. Using CMOS ISFETs provides advantages of digitisation directly at the sensor as well as correcting for non-linearity in its response. However, for this to be beneficial and scale, the readout circuits need to have the minimum possible footprint and power consumption. Within this context, this paper analyses an ISFET based pH-to-time readout using an inverter in the time-domain as a level-crossing detector and presents a 32×32 array with in-pixel digitisation for pH sensing. The inverter-based sensing pixel, controlled by a triangular waveform, converts the pH response into a timedomain signal whilst also compensating for sensor offset and thus resulting in an increase in dynamic range. The sensor pixels interface to a 15-bit asynchronous column-wise time-todigital converter (TDC), enabling fast asynchronous conversion whilst using minimal silicon area. Parallel outputs of 32 TDC interfaces are serialised to achieve fast data throughput. This system is implemented in a standard 0.18 µm CMOS technology, with a pixel size of 26 µm × 26 µm and a TDC area of 26 µm × 180 µm. Additionally, we investigate the use of additional offset compensation by having half of the array implemented with the floating gate tied down via a well diode. Measured results demonstrate the system is able to sense reliably with an average pH sensitivity of 30 mV/pH, whilst being able to compensate for sensor offset by up to ±7 V. A resolution of 0.013 pH is achieved and noise measurements show an integrated noise of 0.08 pH within 2-500 Hz and SFDR of 42.6 dB. The total power consumption of the system is measured to be 11.286 mW when operating at a high frame rate of 1 KFPS.

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ISFETs in CMOS and Emergent Trends in Instrumentation: A Review

Cited by 207 publications

References 79 publications

A novel hotspot specific isothermal amplification method for detection of the common PIK3CA p.H1047R breast cancer mutation

A novel hotspot specific isothermal amplification method for detection of the common PIK3CA p.H1047R breast cancer mutation

Monolayer MoSe₂-Based Tunneling Field Effect Transistor for Ultrasensitive Strain Sensing

Ultrafast Large-Scale Chemical Sensing With CMOS ISFETs: A Level-Crossing Time-Domain Approach

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