Modular transmission line probes for microfluidic nuclear magnetic resonance spectroscopy and imaging

Abstract

Microfluidic NMR spectroscopy can probe chemical and bio-chemical processes non-invasively in a tightly controlled environment. We present a dual-channel modular probe assembly for high efficiency microfluidic NMR spectroscopy and imaging. It is compatible with a wide range of microfluidic devices, without constraining the fluidic design. It collects NMR signals from a designated sample volume on the device with high sensitivity and resolution. Modular design allows adapting the detector geometry to different experimental conditions with minimal cost, by using the same probe base. The complete probe can be built from easily available parts. The probe body mainly consists of prefabricated aluminium profiles, while the probe circuit and detector are made from printed circuit boards. We demonstrate a double resonance HX probe with a limit of detection of 1.4 nmol s −1/2 for protons at 600 MHz, resolution of 3.35 Hz, and excellent B 1 homogeneity. We have successfully acquired 1 H-13 C and 1 H-15 N heteronuclear correlation spectra (HSQC), including a 1 H-15 N HSQC spectrum of 1 mM 15 N labeled ubiquitin in 2.5 µl of sample volume.

High-Resolution Nuclear Magnetic Resonance Spectroscopy with Picomole Sensitivity by Hyperpolarization on a Chip

“…The assembled microfluidic device was put in a transmission line based home-built probe. 11 The device sits between the two detector planes with the sample chamber of the device aligned with the sensitive area of the detector. All NMR experiments were performed at a field strength of 11.7 T with an AVANCE III console.…”

Time-Resolved Non-Invasive Metabolomic Monitoring of a Single Cancer Spheroid by Microfluidic NMR

“…Highly efficient NMR micro-detectors have been developed by a number of groups over the past two decades [12][13][14][15][16][17][18][19] and sensitivities in the vicinity of 1 nmol √ s have been achieved with samples around 1 µL volume 20 . Our group has recently presented a modular microfluidic NMR system based on this detector geometry that accommodates generic LoC devices 21 . A detailed characterisation of its performance is given in Ref.…”

Time-Resolved Non-Invasive Metabolomic Monitoring of a Single Cancer Spheroid by Microfluidic NMR

“…Highly efficient NMR micro-detectors have been developed by a number of groups over the past two decades [5][6][7][8][9][10][11][12] and sensitivities in the vicinity of 1 nmol √ s have been achieved with samples around 1 µL volume [13]. Our group have recently presented a modular microfluidic NMR system that accommodates generic LoC devices [14]. In the present contribution, we show that this makes it possible to quantitatively follow the metabolic activity of as few as 1250 mammalian cells in 2.5 µL of medium over the course of 48h.…”

“…In the present study, we demonstrate that a flexible microfluidic NMR platform can be used to quantitatively compare metabolic data obtained under different experimental modalities. The platform consists of a modular transmission line NMR micro-probe [14] in combination with disposable, generic LoC devices. Human adenocarcinoma cells (MCF-7) [27] were cultured under hypoxic conditions in LoC devices which were coated either with fibronectin, in order to promote adhesion of the cells to the chip surface [28], or with pluronic F-127, which prevents cell adhesion and forces the cells to form a spheroid [29].…”

“…The chips were then sealed with an airtight self-adhesive film, and were transferred to an incubator at 37 • C for a further 44h. At regular intervals, the chips were removed from the incubator and inserted into a NMR spectrometer operating at a proton Larmor frequency of 600 MHz using a specially built transmission line micro-NMR probe [14]. lowest seeding density, only a loose spheroid is obtained, and cell viability at the end of the experiment is poor.…”