A handheld magnetic sensing platform for antigen and nucleic acid detection

Abstract

The core requirements for point-of-care (POC) diagnostics necessitate low-cost, portability, easily integrated sample preparation, and quick measurement time. Frequency-shift based magnetic sensing is a measurement technique utilizing a complementary metal-oxide-semiconductor (CMOS) integrated-circuit (IC) chip for magnetic label detection. The sensing scheme leverages the low-cost manufacturing of IC chips while demonstrating the potential for multiplexing capabilities. In this article, we present modifications to this scheme for POC viability. We introduce a handheld reusable reader and a disposable open-well cartridge for the detection of nucleic acids and antigens. The diagnostic system utilizes a novel "magnetic freezing" technique to reduce measurement time, obviates baseline measurement before or during biological assay, and reduces sensor noise. We utilize these enhancements for the room temperature, amplification-free detection of a 31 base-pair DNA oligomer and the interferon-γ (IFN-γ) protein. We have demonstrated reliable measurements down to 100 pM for the DNA assay and 1 pM for the protein.

Overview of CMOS image sensor use in molecular diagnostics

“…However, the requirement for an expensive array reader limits this tool. Instead, a CMOS image sensor has been as an optical [55], (b) label free DNA detection on slinanized surface [56], (c) DNA, protein and glucose detection on polymer coated surface [57], (d) nucleic acid and antigen detection of magnetic sensing platform [58] (e) protein interaction on silanized surface [59], (f) protein interaction on polymer coated substrate [60], (g) protein detection on microelectronics integrated substrate [53]. reader to identify DNA hybridization [61].…”

CMOS biosensors for in vitro diagnosis – transducing mechanisms and applications

“…5(a)-(c)]. 49 The bound magnetic particles are detected from the oscillation frequency of the oscillator. They demonstrated the detection of DNA with a concentration of 100 pM by a novel magnetic freezing technique to reduce the sensor noise [ Fig.…”

Multi-parametric cell profiling with a CMOS quad-modality cellular interfacing array for label-free fully automated drug screening

“…Most existing cell-based assays utilize single-modality electronic sensors, each of which only measures one cell physiological property. Examples include microelectrode arrays (MEAs) with extracellular potential amplifiers and stimulators for recording neuron activities and action potential conduction, [17][18][19][20][21] electrical impedance sensors for cell-growth assay, cardiac beating measurements, and myocardial ischemia detection, [22][23][24] ion-sensitive field effect transistor (ISFET) arrays for cell metabolism assay, 25,26 magnetic sensor arrays for capturing cardiac beating or molecular detection, 12,16,[27][28][29] and optical sensors for DNA sensing and sequencing. [30][31][32][33][34] However, cells are highly complex systems with concurrent multi-physical activities, and thereby holistic understanding of such complex cellular physiological responses remains a daunting task.…”