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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.

Complementary metal oxide semiconductor (CMOS) technology enables low-cost and large-scale integration of transistors and physical sensing materials on tiny chips (e.g., <1 cm), seamlessly combining the two key functions of biosensors: transducing and signal processing. Recent CMOS biosensors unified different transducing mechanisms (impedance, fluorescence, and nuclear spin) and readout electronics have demonstrated competitive sensitivity for in vitro diagnosis, such as detection of DNA (down to 10 aM), protein (down to 10 fM), or bacteria/cells (single cell). Herein, we detail the recent advances in CMOS biosensors, centering on their key principles, requisites, and applications. Together, these may contribute to the advancement of our healthcare system, which should be decentralized by broadly utilizing point-of-care diagnostic tools.

We report a micro-Nuclear Magnetic Resonance (NMR) system compatible with multi-type biological/chemical lab-on-a-chip assays. Unified in a handheld scale (dimension: 14 x 6 x 11 cm 3 , weight: 1.4 kg), the system is capable to detect < 100 pM of Enterococcus faecalis derived DNA from a 2.5-μL sample. The key components are a portable magnet (0.46 T, 1.25 kg) for nucleus magnetization, a system PCB for I/O interface, an FPGA for system control, a current driver for trimming the magnetic (B) field, and a silicon chip fabricated in 0.18-μm CMOS. The latter, integrated with a current-mode vertical Hall sensor and a low-noise readout circuit, facilitates closed-loop B-field stabilization (2 mT  0.15 mT), which otherwise fluctuates with temperature or sample displacement. Together with a dynamic-B-field transceiver with a planar coil for micro-NMR assay and thermal control, the system demonstrates: 1) selective biological target pinpointing; 2) protein state analysis and 3) solvent-polymer dynamics, suitable for healthcare, food and colloidal applications, respectively.Compared to a commercial NMR-assay product , this platform greatly reduces the sample consumption (120x), hardware volume (175x) and weight (96x). Index TermsBaseband, biological, biosensor, chemical, CMOS, deoxyribonucleic acid (DNA), filter, Hall sensor, immunoglobulin, lab-on-a-chip, low-noise amplifier (LNA), magnetic sensing, nuclear magnetic resonance (NMR), point-of-care, polymer, power amplifier (PA), protein, radio frequency (RF), receiver (RX), transceiver (TRX), transimpedance amplifier (TIA), transmitter (TX).J S S C -M a n u s c r i p t 2 | P a g e