A palm-size μNMR relaxometer using a digital microfluidic device and a semiconductor transceiver for chemical/biological diagnosis

Abstract

Herein, we describe a micro-nuclear magnetic resonance (μNMR) relaxometer miniaturized to palm-size and electronically automated for multi-step and multi-sample chemical/biological diagnosis. The co-integration of microfluidic and microelectronic technologies enables an association between the droplet managements and μNMR assays inside a portable sub-Tesla magnet (1.2 kg, 0.46 Tesla). Targets in unprocessed biological samples, captured by specific probe-decorated magnetic nanoparticles (NPs), can be sequentially quantified by their spin-spin relaxation time (T2) via multiplexed μNMR screening. Distinct droplet samples are operated by a digital microfluidic device that electronically manages the electrowetting-on-dielectric effects over an electrode array. Each electrode (3.5 × 3.5 mm(2)) is scanned with capacitive sensing to locate the distinct droplet samples in real time. A cross-domain-optimized butterfly-coil-input semiconductor transceiver transduces between magnetic and electrical signals to/from a sub-10 μL droplet sample for high-sensitivity μNMR screening. A temperature logger senses the ambient temperature (0 to 40 °C) and a backend processor calibrates the working frequency for the transmitter to precisely excite the protons. In our experiments, the μNMR relaxometer quantifies avidin using biotinylated Iron NPs (Φ: 30 nm, [Fe]: 0.5 mM) with a sensitivity of 0.2 μM. Auto-handling and identification of two targets (avidin and water) are demonstrated and completed within 2.2 min. This μNMR relaxometer holds promise for combinatorial chemical/biological diagnostic protocols using closed-loop electronic automation.

µ‐NMR at the point of care testing

“…By introducing CMOS ICs into an NMR‐DMF system, the NMR detection device could be further reduced to palm‐size with improved sensitivity as well, because the integration of discrete electronics on the CMOS eliminated the potential for mutual interference . In the following year, Lei and the group proposed the first palm‐sized µNMR relaxometer for chemical and biological diagnosis (shown in Fig. ).…”

“…(B) The brief assembly of the DMF device. Reprinted with permission from . Copyright The Royal Society of Chemistry 2015.…”

Portable nuclear magnetic resonance biosensor and assay for a highly sensitive and rapid detection of foodborne bacteria in complex matrices

“…The development of high-throughput NMR spectrometers using complementary metal oxide semiconductor (CMOS) technology consisted of an array of high sensitivity micro-coils integrated with interfacing radio-frequency circuits on the same chip [10]. A micro-nuclear magnetic resonance (μNMR) relaxometer miniaturized to palm-size and electronically automated for multi-step and multi-sample chemical/biological diagnosis was also developed [11]. The μNMR relaxometer integrated microfluidic and microelectronic technologies to enable the association between the droplet management and μNMR assay inside a portable sub-Tesla magnet.…”

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

“…However, if the magnetic field fluctuates large enough such that the excitation pulses cannot excite the nucleus effectively, those calibration schemes may not work properly. Previously, we reported a calibration scheme to detect the ambient temperature and then tune the LO accordingly [28]. This method, however, suffers from a delay between the ambient temperature variation and the response on the magnet due to its high heat capacity (time constant >10 mins).…”