28.1 A handheld 50pM-sensitivity micro-NMR CMOS platform with B-field stabilization for multi-type biological/chemical assays

Abstract

Point-of-use (PoU) biological/chemical assays are aimed to transform bulky laboratory instruments into easy-to-use lab-on-a-chip platforms, bringing down the cost, size, and sample-use by orders of magnitude [1,2]. Micro-Nuclear Magnetic Resonance (NMR) is a trail-blazing tool for target pinpointing, by utilizing functionalized magnetic nanoparticles (MNPs) as the probe [3]. Screening by micro-NMR is repeatable, versatile and low-cost as it is label-and washingfree for the samples, and immobilization-free for the electrodes. Herein, a high-sensitivity micro-NMR CMOS platform with magnetic (B)-field stabilization and thermal management is reported (Fig. 28.1.1). This handheld tool unifies multi-type assays (target detection, protein state analysis, and solvent-polymer dynamics), and is suitable for healthcare, food industry, and colloidal applications.Micro-NMR relaxometry detects the spin-spin relaxation time (T 2 ) by extracting the echoes envelopes from the response of the non-zero spin nuclei (i.e., 1 H). The nuclei, under magnetization with a static magnetic field (B 0 ), absorb orthogonal RF exciting magnetic field (B 1 ) at the Larmor frequency, f L =γB 0 (γ: gyromagnetic ratio), and precess about the direction of magnetization at f L even after the cessation of the excitation. In an existing micro-NMR system [3], frequency deviation of the local oscillator (LO) from f L induces improper frequency excitation, paralyzing the operation. Confounded by the thermal instability of the portable magnet (B 0 =0.46T, T.C.=-1200ppm/K), LO tracking is essential to safeguard the system against environmental changes.Our micro-NMR platform ( Fig. 28.1.2) is tailored with B 0 -field stabilization and thermal management to enhance the robustness and simplify the hardware. The dynamic B 1 -field transduction is based on a spiral coil driven by a transmitter (TX)/receiver (RX) together with a matching capacitor C M , to excite/obtain the magnetic signal to/from the droplet samples (2.5μL) normal to the chip surface. The TX is based on a tapped inverter-chain power amplifier (PA), measured 31.6% power efficiency, to deliver programmable pulse sequences pertaining to the LO. The RX features a multi-stage low-noise amplifier (LNA) for high RX sensitivity (down to 1nV/√Hz input-referred-noise), and a dynamic-bandwidth lowpass filter for fast recovery from saturation after excitation pulses. The B 0 -field sensor and calibrator manage the lateral B 0 -field together with a current driver, which injects a calibration current to the magnet (75mT/A) stabilizing the bulk magnetization on the nuclei. The spiral coil also serves as a heater allowing thermal profiling of the samples. The thermal-induced error on the B 0 -field sensor and calibrator, and the hotness of the samples, are monitored by a BJT temperature sensor.To sense the lateral B 0 -field normal to the chip surface, a current-mode 4-folded vertical hall sensor (VHS) arranged in a Wheatstone bridge is employed (Fig. 28.1.3). Each VHS element is composed by an n-well as the...

Introduction

“…Chapter 4 discloses the design of the micro-NMR relaxometer with B 0 -field stabilization module [36,37]. Ascribed to the temperature instability of the magnet, calibration on either excitation frequency or Larmor frequency of the protons is necessary to safeguard the operation of the micro-NMR relaxometer.…”

CMOS Vertical Hall Magnetic Sensors on Flexible Substrate

“…A well laid out geometry of the Hall device can greatly decrease the offsets and improve the performance. For a 4F 3C VHS, the spinning circuitry design for two-phases operation has been reported in [31]. This design uses four phases, as shown in Fig.…”

A Handheld High-Sensitivity Micro-NMR CMOS Platform With B-Field Stabilization for Multi-Type Biological/Chemical Assays

“…This work was presented in IEEE ISSCC 2016 [24]. Here we disclose the entire design and engineering of the platform.…”