Hybrid AFM/NMR Probe for Nanoscale Single-Cell Imaging
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Solution Overview
Problem
Current imaging technologies, such as NMR, have limited spatial resolution and long acquisition times, making it difficult to analyze cellular structures and local biochemistry at the single cell level, which is essential for understanding cellular disease mechanisms and developing treatments.
Innovation Solution
A hybrid AFM/NMR probe that combines atomic force microscopy and nuclear magnetic resonance technologies, enabling nanoscale spatial localization and biophysical analysis, with a nanofabricated planar radiofrequency coil for localized spectroscopy and cell localization, allowing for real-time biophysical, chemical, and structural analysis of single cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional NMR imaging is used, then tissue morphology and function can be imaged, but spatial resolution is limited to about 1.0 micron and volume elements to less than 64 μm3, preventing single cell-level analysis
Solution Approach 1:
The patent divides the NMR imaging system into two independent components: a conventional NMR imaging system for bulk tissue analysis and a separate micro-NMR probe for single-cell analysis. This segmentation allows each component to be optimized for its specific resolution requirements without compromising the other, enabling both macro and micro imaging capabilities within the same overall system.
Solution Approach 2:
The patent introduces a new spatial dimension by integrating a micro-NMR probe that can be positioned at the single-cell level within tissue samples. This micro-probe operates independently from the conventional NMR scanner, adding a microscopic imaging dimension to the existing macro imaging capability, thereby achieving multi-scale analysis from whole tissue to individual cells.
2Productivity
If conventional NMR imaging is used, then tissue morphology can be visualized, but acquisition times are long (approximately 8 hours), reducing productivity
Solution Approach 1:
The patent segments the imaging task into two separate processes: rapid micro-NMR spectroscopy for single-cell biochemical analysis and conventional NMR imaging for tissue morphology. The micro-NMR probe can perform rapid acquisitions in minutes rather than hours, significantly improving productivity for cellular-level studies while the conventional scanner handles bulk tissue characterization.
Solution Approach 2:
The patent applies partial action by using the micro-NMR probe to perform rapid biochemical analysis of individual cells or small regions, obtaining sufficient information for cellular characterization without requiring the full conventional NMR imaging sequence. This partial analysis approach dramatically reduces acquisition time while providing the necessary cellular-level insights.
3Adaptability or versatility
If single cell-level analysis is performed, then cellular heterogeneity and disease mechanisms can be investigated, but current technologies cannot simultaneously provide mechanical, structural, and biochemical information
Solution Approach 1:
The patent merges three distinct analytical capabilities into a single integrated platform: AFM for mechanical properties and surface morphology, Raman spectroscopy for biochemical composition, and micro-NMR for molecular structure and dynamics. By combining these techniques in one system with a single probe, the patent enables simultaneous multi-parameter analysis of single cells, providing comprehensive insights into both mechanical and biochemical characteristics without requiring multiple separate measurements.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The hybrid probe achieves high-resolution imaging and spectroscopy of individual cellular structures, improving the detection of cellular heterogeneity and providing valuable insights into cellular disease mechanisms, leading to more effective treatments and therapies.
Implementation Method 1
at least one piezoelectric element mounted to the top surface of the beam at or near the proximal end, where the at least one piezoelectric element is capable of generating a deflection signal due to strain in the beam due to a deflection of the distal end
Implementation Method 2
a coil having at least one turn mounted to the top surface of the beam at or near the distal end opposite the tip, where the coil is capable of both transmitting and sensing electromagnetic radiation
Implementation Method 3
when positioned within a magnetic field, is capable of nuclear magnetic resonant spectroscopy by transmission to and reception of electromagnetic radiation from the sample via the coil
Data Source
AI summary
A method of using a AFM/NMR probe, the method comprising the steps of injecting a sample to be analyzed with magnetic particles, introducing a probe into proximity with the sample, the probe capable of both transmitting and sensing electromagnetic radiation; generating a magnetic field via the probe, and adjusting the magnitude of the magnetic field to manipulate the magnetic particles within the sample.