Deterministic Mechanoporation with Static Needle for Viable Cell Delivery
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Solution Overview
Problem
Existing methods for intracellular delivery of exogenous materials to large populations of suspension cells are inefficient and often compromise cell viability, necessitating high-throughput and precise delivery techniques.
Innovation Solution
A system and method for precision mechanoporation using a static array of wells with gravitational sedimentation and flow-focusing to capture single cells, combined with a static needle for cargo injection without centrifugation or needle movement, enabling pressure-driven flow and localized cargo delivery into the cell nucleus.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional intracellular delivery methods are used, then cargo delivery can be achieved, but cell viability is compromised and throughput is low
Solution Approach 1:
The system divides the cell population into individual single-cell compartments within an array of wells, allowing parallel processing of millions of cells simultaneously. Each well contains a single cell that is independently captured, mechanoporated, and delivered, enabling high throughput while maintaining individual cell viability through controlled, localized treatment
Solution Approach 2:
The invention changes the physical state and arrangement of cells from a bulk suspension to individual trapped cells in microwells. This parameter change enables precise control over delivery parameters for each cell while processing large populations, resolving the contradiction between throughput and viability by making viability controllable at the single-cell level across millions of cells
2Quantity of substance
If centrifugation is used for cell capture, then cell concentration can be achieved, but system complexity and energy consumption increase
Solution Approach 1:
The system replaces the mechanical centrifugation system with a microfluidic pressure-driven flow system. Cells are concentrated and sorted through controlled fluid flow and pressure gradients within the microwell array, eliminating the need for centrifugal force generation, large-scale mechanical components, and high energy consumption associated with centrifugation
Solution Approach 2:
The invention uses pressure-driven fluid flow and pneumatic control to achieve cell capture and concentration. By applying controlled pressure gradients through microfluidic channels, cells are directed into individual wells without mechanical centrifugation, reducing system complexity and energy requirements while maintaining effective cell concentration
3Manufacturing precision
If moving needles are used for cargo injection, then delivery precision can be improved, but device complexity and operational difficulty increase
Solution Approach 1:
Instead of moving the needle to achieve precise delivery, the invention inverts the approach by keeping the needle stationary and moving the cell into the needle's position. The cell is captured in a microwell directly over the static needle, then mechanically engaged and delivered without needle movement, simplifying the device while maintaining precision
Solution Approach 2:
The system performs preliminary capture of the cell in the microwell positioned over the static needle before delivery. This preliminary positioning action ensures precise alignment and cell-needle engagement without requiring the needle to move, thereby achieving delivery precision while maintaining operational simplicity through the static needle design
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 system achieves high throughput and efficient cargo delivery with minimal cell viability loss, ensuring at least 70% cell viability and uniform cargo load across processed cells, with a coefficient of variability below 10%, and capable of processing millions of cells per cycle.
Implementation Method 1
one or more modules for generating a pressure gradient, wherein the pressure gradient is configured to induce a pressure-driven flow of a single cell suspension in the system
Implementation Method 2
each well of the array of wells is configured to capture a single cell therein via sedimentation (e.g., gravitational sedimentation) and flow-focusing of the single cell
Implementation Method 3
a static needle in the bottom surface of each well of the static array of wells configured to inject a cargo into the nucleus of the single cell captured in the well
Data Source
AI summary
Described are systems, devices, and methods for delivery of a payload to a cell, including gene transfection of the cell. Such systems, devices, and methods are configured to capture and form a pore in a cell through which the payload may be delivered. Additionally, such systems, devices and methods are configured to work with various cell types and to deliver the payloads to the nucleus of the cell.