Ballistic Microscopy for Live-Cell Pico-Sampling and Omics Imaging
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current imaging and sampling techniques for cell contents are limited by destructive methods that provide only static snapshots, lack spatial resolution, and cannot capture dynamic cellular processes in live cells.
Innovation Solution
Ballistic microscopy (BaM) uses high-speed ballistic nanoparticles to capture pico- to femto-liter samples from live cells without harm, enabling high spatial and temporal resolution imaging by combining with mass spectrometry or sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If label-free approaches like cryo-electron microscopy are used to obtain atomic resolution imaging, then structural detail is improved, but the sample is frozen in a single static state and dynamic cellular processes cannot be captured
Solution Approach 1:
The cell is sampled at multiple discrete time points through repeated ballistic particle bombardment, dividing the dynamic process into sequential snapshots that can be reconstructed into a temporal movie, thereby achieving both atomic resolution and temporal resolution
Solution Approach 2:
Live cells are pre-cultured and maintained in physiological conditions before bombardment, allowing dynamic processes to occur naturally before being captured at specific time points, preserving the temporal sequence of cellular events
2Measurement precision
If mass spectrometry is used to decipher molecular identities, then molecular identification is improved, but spatial resolution is limited and the sample is destroyed
Solution Approach 1:
Ballistic particles serve as intermediaries that physically extract molecular material from specific spatial locations within the cell and transport it to the mass spectrometry analyzer, preserving spatial information while enabling molecular identification
Solution Approach 2:
Ballistic particles extract and remove molecular material from the cell at specific locations, separating the sampling function from the analysis function, thereby preserving spatial resolution information while enabling comprehensive molecular identification through mass spectrometry
3Length of stationary object
If high-velocity particles are used to penetrate thick tissues, then penetration depth is improved, but the complexity of the system increases
Solution Approach 1:
The velocity of ballistic particles is varied as a controllable parameter to adjust penetration depth, allowing the same system to image different tissue thicknesses by simply changing the acceleration voltage or particle launch speed, without requiring different hardware systems
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
Enables dynamic, atomic-scale imaging of live cells with unprecedented detail, allowing untargeted identification and localization of unknown analytes in both space and time, applicable to a wide range of cell types and tissues.
Implementation Method 1
These are ballistic micro and nano particles that travel through a cell at ballistic speed and capture a pico or femto-liter of cellular content and bring it out for analysis
Data Source
AI summary
Ballistic microscopy—a completely new approach to “image” a cell utilizing particle bombardment, is described. These are ballistic micro and nano particles that travel through a cell at ballistic speed and capture a pico or femto-liter of cellular content and bring it out for analysis without harming the cell. This enables a new approach to omics-based imaging where millions of these particles are bombarded on cells with resolved space and time and captured to process using well known omics techniques including proteomics (mass spec) or sequencing—while keeping the spatial and temporal resolution. This work provides—for the first time—a way to resolve atomic details of live cells without any labels.