Automated Tissue Section Collection Apparatus

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Solution Overview

Problem

Current methods for creating a comprehensive wiring diagram of the brain are hindered by the manual and time-consuming process of producing thin tissue slices for imaging, which is impractical for larger brain structures like those of rodents and humans, due to the fragility and handling requirements of the tissue sections.

Innovation Solution

An automated system for collecting and handling thin tissue sections, including a collection apparatus that moves in conjunction with a microtome to collect sections without manual intervention, maintains fluid levels, and adjusts the speed of the support substrate to match sectioning rates, enabling prolonged and precise collection of thin tissue sections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If manual collection methods are used, then tissue sections can be collected, but tissue damage occurs and the process is time-consuming

Engineering Contradiction:

Improvetissue section integrityVSAvoidcollection time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The system enables automated self-collection of tissue sections through the microtome's integrated collection apparatus, eliminating the need for manual technician intervention. The collection mechanism automatically retrieves sections from the water boat and transfers them to the support substrate continuously during the sectioning process.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The manual mechanical manipulation by technicians is replaced with an automated mechanical collection system. The apparatus uses mechanical means to automatically retrieve tissue sections from the water boat and deposit them onto the support substrate, replacing the manual eyelash technique with a systematic mechanical collection process.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If manual collection is used, then tissue sections can be retrieved, but the ultramicrotome must be frequently stopped

Engineering Contradiction:

Improvecollection operationVSAvoidsectioning throughput

Core Design Contradiction:

Ease of operationVSProductivity

Solution Approach 1:

The collection apparatus operates continuously throughout the sectioning process, allowing the ultramicrotome to run without interruption. The system maintains continuous collection of tissue sections on the support substrate, eliminating the need to stop the sectioning process for manual retrieval operations.

Inventive Principle:

Principle #20Continuity of useful action

3Productivity

If thicker tissue sections are cut to compensate for disturbances, then collection can continue, but imaging resolution is limited

Engineering Contradiction:

Improvecontinuous sectioning capabilityVSAvoidimaging resolution

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The system provides continuous feedback through the automated collection process, allowing real-time monitoring of section quality and thickness. This enables maintenance of optimal thin section thickness (50-200 nm) throughout prolonged sectioning runs, as the automated system can detect and compensate for variations to maintain consistent section quality suitable for high-resolution imaging.

Inventive Principle:

Principle #23Feedback

4Ease of manufacture

If manual collection is performed, then tissue sections can be gathered, but skilled technicians are required and damage is inevitable

Engineering Contradiction:

Improvecollection process simplicityVSAvoidtissue section preservation

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The system provides protective cushioning for fragile tissue sections through the water boat environment and controlled collection mechanism. The water provides a cushioning medium that supports tissue sections during retrieval, while the automated mechanism handles sections gently to prevent damage that would occur with manual manipulation.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

Data Source

PatentEP2614376B1Methods and systems for collection of tissue sections

Publication Date: 2022.11.02 PRESIDENT & FELLOWS OF HARVARD COLLEGE

Figure 1A~1C
Figure 2A~2B
Figure 3A~3C

AI summary

Methods, apparatuses and systems for facilitating automated or semi- automated collection of tissue samples cut by a microtome. In one example, a collection apparatus may be moved back and forth between respective positions at which the collection apparatus is operatively coupled to a microtome so as to collect cut tissue samples, or routine access to the microtome is provided. Relatively easy movement and positioning of the collection apparatus is facilitated, while at the same time ensuring structural stability and appropriate alignment and/or isolation between the collection apparatus and the microtome. A fluid reservoir receives samples cut by the microtome, and the collection apparatus may collect samples via a conveyor-like substrate disposed near/in the reservoir. A linear movement of the substrate may be controlled based on a cutting rate of the microtome, and the fluid level in the reservoir may be automatically maintained to facilitate effective sample collection.