A Scalable ISFET Sensing and Memory Array With Sensor Auto-Calibration for On-Chip Real-Time DNA Detection

Abstract

This paper presents a novel CMOS-based system-on-chip with a 78 56 ion-sensitive field-effect transistor array using in-pixel quantization and compensation of sensor nonidealities. The pixel integrates sensing circuitry and memory cells to encode the ion concentration in time and store a calibration value per pixel. Temperature sensing pixels spread throughout the array allow temperature monitoring during the reaction. We describe the integration of the array as part of a lab-on-chip cartridge that plugs into a motherboard for power management, biasing, data acquisition, and temperature regulation. This forms a robust ion detection platform, which is demonstrated as a pH sensing system. We show that our calibration is able to perform readout with a linear spread of 0.3% and that the system exhibits a high pH sensitivity of 3.2 /pH. The complete system is shown to perform on-chip real-time DNA amplification and detection of lambda phage DNA by loop-mediated isothermal amplification.

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

“…Owing to their compatibility with CMOS technology (complementary metal-oxide-semiconductor), fully-electronic chemical detection is possible while ensuring sensor miniaturisation, mass manufacturing and low cost. CMOS-based ISFET sensing has been demonstrated for the detection of DNA amplification by employing an adapted version of LAMP, called pH-LAMP, that allows changes in pH to occur during nucleic acid amplification such that they can be detected by the ISFET sensors [32][33][34]. Furthermore, this technology is a suitable candidate for point-of-care implementations through transferring the amplification chemistries on a Lab-on-Chip platform with integrated sensing.…”

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

“…In optical imaging, Active Pixel Sensor (APS) based readouts simplify the inpixel structure, together with column or array-level Correlated Double Sampling (CDS) for reducing mismatch in the sensor output. This architecture has also been applied to chemical sensing arrays [6], [7], [10]. Here, the voltage on the floating gate is converted to a current, with a sampling capacitor being charged via a source-follower or common source configuration.…”

“…Furthermore, compensation schemes for sensor offset are usually performed via resetting the floating gate voltage or by biasing the reference electrode. This poses a challenge for continuous monitoring applications that require fully-integrated biasing [6], [7], [11].…”

“…1. Typical ISFETs readout circuits with dashed boxes indicating the in-pixel structure: (a) Source drain follower [13]; (b) time-based readout with current discharging output nodes [6]; (c) PWM-based interface with time output [12]; (d) in-pixel common-source configuration with external interface [10]; (e) Closed-loop readout with ISFETs within the loop [11].…”

Simultaneous single-channel multiplex and quantification of carbapenem-resistant genes using multidimensional standard curves

“…will greatly expand the applicability of emerging molecular technologies (3,4), including point-of-care settings. Invasive infections with carbapenemase-producing strains are associated with high mortality rates (up to 40 -50%) and represent a major public health concern worldwide (5, 6).…”