Fixed-Target Sample Holder for High-Throughput Synchrotron Crystallography

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

The bottleneck in biomolecular crystallography is obtaining and handling small, highly ordered crystals for X-ray analysis, which is exacerbated by radiation damage and inefficient sample handling methods, leading to low throughput and high costs in structure determination.

Innovation Solution

A flexible, modular sample handling system for serial synchrotron X-ray crystallography that integrates with existing infrastructure, allows multiple loading modalities, provides environmental control, and minimizes X-ray background scatter, enabling rapid prototyping and high-throughput crystallography.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If small crystals are used for X-ray analysis, then radiation damage increases and sample handling becomes more difficult, but throughput must be increased to meet structural determination demands

Engineering Contradiction:
ImprovethroughputVSAvoidradiation damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The system segments the sample handling process into modular components: a sample holder with multiple sample positions, an automated sample changer, and individual crystal mounting positions. This allows parallel processing of multiple crystals, increasing throughput while each crystal receives controlled, minimal X-ray exposure to reduce radiation damage.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Crystals are pre-mounted on loops or pins in a controlled environment before being transferred to the X-ray beamline. This preliminary preparation allows optimization of crystal orientation and positioning before data collection, reducing the time each crystal needs to be exposed to X-rays and minimizing radiation damage while maintaining high throughput.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If traditional sample handling methods are used, then sample preparation and exchange time increases, but high throughput crystallography is required

Engineering Contradiction:
ImprovethroughputVSAvoidsample preparation and exchange time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The system employs dynamic, automated sample exchange mechanisms where crystals can be rapidly transferred between mounting positions and the X-ray beam without manual intervention. The automated sample changer dynamically adjusts sample positions and orientations, reducing preparation and exchange time while maintaining high throughput crystallography.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The sample holder and automated sample changer are designed to perform self-alignment and self-positioning functions, reducing the need for manual adjustment and preparation time. Crystals are automatically oriented and positioned in the X-ray beam, enabling high throughput operation with minimal human intervention.

Inventive Principle:
Principle #25Self-service

3Object-affected harmful factors

If crystals are cooled to reduce radiation damage, then additional disorder is introduced, but radiation damage must be minimized

Engineering Contradiction:
Improveradiation damageVSAvoidcrystal order
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The system optimizes multiple parameters simultaneously: cooling temperature, X-ray beam intensity, exposure time, and crystal orientation. By carefully adjusting these parameters, the system minimizes radiation damage through controlled cooling while maintaining crystal order through optimized exposure conditions and rapid data collection protocols.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS12436116B2Serial synchrotron crystallography sample holding system
Publication Date: 2025.10.07 MITEGEN LLC
  • US12436116B2 patent drawing
  • US12436116B2 patent drawing
  • US12436116B2 patent drawing

AI summary

A fixed target sample holder for serial synchrotron crystallography comprising goniometer compatible base, a carrier, a sample holding insert which can be placed into the carrier. The sample holing insert comprising fiducials and windows, wherein each of the windows are respectively configured to accept a sample. The windows can also have holes and texture within each window. Additionally, a sample loading workstation for loading crystals into the sample holder and the removal of excess liquid from the sample, comprising a humidity-controlled chamber, a sample support within the chamber, a capture to place the goniometer-compatible base and a channel in communication with the chamber that allows for the flow of humidified air into the chamber.