We have developed new types of magnetic sensors for clinical diagnostics. Magnetic detection can be highly selective even in complex biological media because of the inherently negligible magnetic background of biological objects. As such, the need for extensive sample purification is obviated, which not only minimizes sample loss, but also simplifies assay procedure.
Diagnostic Magnetic Resonance (DMR)
DMR Platform. (a) Iron-based magnetic nanoparticles. (b) Array of microcoils as an NMR probe. © Microfluidic chip integrating sample processing units and a NMR probe. (d) Miniaturized DMR system for clinical applications.
detection is based on the “T2-shortening” effect of magnetic nanoparticles (MNPs) in NMR
measurements. When placed in static polarizing magnetic fields for NMR
detection, MNPs produce local dipole fields that efficiently destroy the coherence in the spin-spin relaxation of water protons. MNP
-labeled objects consequently cause faster decay of the NMR
signal, or a shorter transverse relaxation time (T2), than do non-targeted objects. Significant advances have been made to improve the DMR
technology: 1) new types of MNPs with high magnetic moments were synthesized; 2) NMR
probes were integrated with sophisticated microfluidics to enable on-chip sample processing and NMR
detection; 3) the entire NMR
system was miniatured into a portable system for point-of-care operations in clinical settings. The developed DMR
platforms have been applied to detect various biological targets, including low levels of proteins (~10 pM), scant numbers of bacteria, single tumor cells, and exosomes.
The microHall (µHall) is a new cellular detection system that can quantitatively screen individual cells in unprocessed clinical specimens. The system uses a miniaturized Hall sensor to detect the magnetic moments of cells that have been immunolabeled with MNPs. The assay is performed on a single microfluidic chip, thereby eliminating the need for expensive or bulky equipment (e.g., optics or centrifuges).
First μHall prototype. (Left) Zoom up of microHall elements. (Right) Packaged μHall chip with microfluidics on top.
The fabrication of Hall sensors is also fully compatible with standard semiconductor processing, which consequently enables low-cost mass production of sensor chips as well as their integration with other auxiliary electronics. When compared with conventional flow cytometry, the µHall platform showed excellent agreement in molecularly screening cells. Importantly, the sensor was able to detect individual cells even in the presence of vast numbers of blood cells and unbound reactants. This capability renders the µHall well-suited for rare cell detection in complex biological media. For example, in a clinical trial with cancer patient blood samples, the µHall detected circulating tumor cells in all patient samples, even those that tested negative with clinical standards.