Analysis of System Design Scheme for Detection of Separated Rare Cells Based on LabVIEW

Challenge: Design, develop, and manufacture a tool that detects and separates circulating tumor cells (CTCs) or fetal cells in maternal blood. The former aims to study individualized treatment in oncology, and the latter is to achieve non-invasive production. Pre-diagnosis.

Solution: Developed a patented technology called "Chip Lab" that utilizes the microelectronic properties of active silicon substrates to create microbiology labs that operate separately on suspended cells with NI embedded controllers.

Silicon Biosystems' technology is based on the ability of an electric field to exert a force on neutrally polarizable particles (such as cells) suspended in a liquid. According to this electrokinetic principle called Dielectrophoresis (DEP), neutral particles in a non-uniform electric field are subjected to a spatial electric field strength along (positive) dielectrophoresis (pDEP) or (negative) dielectrophoresis (nDEP). Reduce the force of the direction. More specifically, a particle is subjected to a positive dielectrophoretic force or a negative dielectrophoretic force due to its own electrical properties, which depends on the frequency and the properties of the medium in which the particles are suspended (Fig. 1).

Analysis of System Design Scheme for Detection of Separated Rare Cells Based on LabVIEW

In the DEPArray system, an electric field is generated on the surface of a silicon chip (Fig. 2a) that is directly connected to a microfluidic cavity in which the cells are suspended. The microfluidic cavity is enclosed by the surface of the chip and a transparent cover that is tens of microns from the surface of the chip. The surface of the active chip implements a two-dimensional array of microcells, each consisting of a planar electrode and an integrated logic circuit (Fig. 2b). When placed in the area corresponding to the electrodes, each electrode can be programmed to create a potential well or dielectric cage. In each of the dielectric cages, the particles can be in a stable suspension state for separate analysis. Because each cell is analyzed separately, the system enables complex fluorescence-based analysis to identify unique characteristics that distinguish target cells from other thousands of contaminated cells. The target cells are able to be independent, but are also simultaneously moved to a certain area of ​​the chip where the microfluidics control them automatically.

DEPArray system

Our patented platform DEPArray is a flexible and easy to use advanced technology system (Figure 4). At the heart of the system is a microchip that integrates an array of 300,000 electrodes in a microfluidic circuit.

The DEPArray system uses National Instruments hardware and software to manage high-precision mechanical, microfluidic, off-the-shelf commercially available electronics and custom tools, as well as vision and image processing. The workflow that the system allows the user to summarize is summarized as the following basic steps:

* Loading samples by microfluidic control

* Get images in bright field and fluorescence

* Analyze the image

* Identify and select target cells through a graphical user interface

* Automatically classify identified target cells

* Recycling target cells by microfluidic control

Sample loading

Sample loading is a very delicate process. We use NI LabVIEW software to control the pump unit to produce the desired pressure gradient so that the sample flows from the inlet slot to the chip within the microfluidic chamber. The system uses algorithms developed by the vision library of the NI Vision Development Module to automate the monitoring and control of the loading process.

Capture and analysis

Once the sample is loaded onto the chip, LabVIEW controls all of the I/O lines, configures the electrode array, holds the cells in cages, and keeps them floating at all stages of the process, ensuring robustness and reliability. System control.

Sample analysis is achieved by optically scanning the surface of the chip with fluorescence and multiple filters in bright field. LabVIEW controls the processing system with the chip and captures, images, and visualizes high-precision digital images acquired from the microscope with micron-level accuracy.

Target cell selection

In this step, the DEPArray system provides users with a powerful Human Machine Interface (HMI) developed by LabVIEW in conjunction with the Microsoft .NET framework to classify and select target cells (Figure 3). Cells can be analyzed using different methods to verify their properties. The HMI displays a scatter plot or histogram that analyzes the measurement results and provides a list of all measurements on the image. For each cell selected, the images captured in the analysis are also displayed, allowing the user to combine the results of the computer measurements with the morphological assessment.

Automatic classification

In this step, based on cell maps and obstacles, LabVIEW dynamically configures the array of chip electrodes to individually and simultaneously move each cell of interest from the initial position to the collection point. Digitization controls the movement of each cell of interest, giving the system high purity and unparalleled performance.

Recycling

In this step, LabVIEW interacts with the peristaltic pump device to create the desired pressure gradient that causes the buffer portion of the selected medium (such as a well or slide in the microfluidic chamber) to flow downwards. The classification and recovery process can be repeated to collect multiple cells or groups of purified cells separately for genetic analysis using traditional molecular biology techniques.

in conclusion

Silicon Biosystems develops technology that leverages NI hardware and software and Sky Technology's technology to provide a set of research activities to isolate circulating tumor cells (CTCs) for individualized treatment in oncology. And identify fetal cells in maternal blood for non-invasive prenatal diagnosis.

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