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

摘要

Herein, we describe a micro-nuclear magnetic resonance (mu NMR) 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 mu NMR 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 (T-2) via multiplexed mu NMR 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 x 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 mu L droplet sample for high-sensitivity mu NMR screening. A temperature logger senses the ambient temperature (0 to 40 degrees C) and a backend processor calibrates the working frequency for the transmitter to precisely excite the protons. In our experiments, the mu NMR relaxometer quantifies avidin using biotinylated Iron NPs (Phi: 30 nm, [Fe]: 0.5 mM) with a sensitivity of 0.2 mu M. Auto-handling and identification of two targets (avidin and water) are demonstrated and completed within 2.2 min. This mu NMR relaxometer holds promise for combinatorial chemical/biological diagnostic protocols using closed-loop electronic automation.