Cell therapy is one of the three pillars of future medicine, and the global flow cytometry market is growing at a healthy rate. According to the Market Research Report, the global market of flow cytometry is expected to reach US $7 billion in 2022. This time, we invited Qian Gong, a senior engineer in the industry, through the technical distributor Excelpoint Shijian to share his practical experience – the hardware design scheme of flow cytometry analyzer.

1. General

Flow cytometry analyzer is a medical in vitro diagnostic equipment for quantitative analysis and sorting of single cells by flow cytometry. Flow cytometry is a high-tech product of immunocytochemistry, hydrodynamics, laser optics, electronics and computing science. Flow cytometry analyzer is mainly composed of optical system, liquid path system, signal detection system and data transmission analysis system. It has the advantages of high speed, high precision and high accuracy. It is the most advanced cell quantitative analysis instrument in modern times.

2. Design considerations and key points at the hardware level

The system integration of flow cytometry analyzer is complex, including fluid control system (controlling sample movement and waste liquid discharge), optical system (light source and optical signal receiving and detection), electrical signal processing system (photoelectric signal conversion and electrical signal filtering and amplification), environmental monitoring and control system (monitoring temperature, humidity, pressure, etc. and carrying out corresponding control), power management system (power supply of each circuit sub module) Data processing system (running algorithm to analyze data), etc.

2.1. Based on the system characteristics of flow cytometry analyzer, the following design points must be considered:

  • High speed and high precision analog signal processing
  • Temperature control is very important for cell and measurement
  • High precision automatic control (temperature, liquid level, mechanical action, etc.)

2.2. Key points of hardware design of analog electrical signal processing system

  • The transimpedance amplifier of current voltage conversion needs low bias current, high input impedance, low noise and low offset operational amplifier
  • High speed, high precision, synchronous sampling ADC
  • Low noise and stable high PSRR power supply
  • Low noise and dynamically adjustable laser constant current source
  • 2.3. Key points of hardware design of environmental monitoring system
  • High precision temperature acquisition device
  • Stable and efficient heating / cooling controller
  • Accurate liquid level measuring device

3. Detailed hardware scheme design

3.1. Analog electrical signal processing system

3.1.1. Hardware scheme of main signal link

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The laser is incident on the cell sheath flow channel, and the scattered light is received by three PDS at different angles. The photocurrent is converted by current and voltage, amplified by program control, and then collected by ADC. Due to the synchronization of three signals and high sampling rate, high-speed parallel ADC needs to be selected and controlled by FPGA to realize high-speed parallel synchronous acquisition.

Selection table of main components





3.1.2. Hardware scheme of laser constant current source with low noise and dynamic adjustment

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The general operational amplifier ad8542 and n-channel MOS tube constitute a constant current source to drive the laser tube. Using the PD feedback of the laser, the constant power source current is adjusted in real time to stabilize the laser output. Through the adjustable resistor RP1, the constant current source current can also be manually adjusted to control the laser power.

3.2. Environmental monitoring system

3.2.1. Temperature control system

The temperature control system is divided into two parts: refrigeration and heating. The refrigeration part is used to store reagents, and the heating part is used to test the thermal insulation of components (constant temperature 37 ℃). Based on the characteristics of Peltier, heating and refrigeration can be applied (just exchange the current direction). This scheme adopts ADI’s single chip scheme (adn8834):

  • Built in low internal resistance H-bridge
  • Built in Tec voltage and current detection circuit
  • It can drive NTC and RTD temperature sensors
  • Two built-in high-performance operational amplifiers can be used for temperature setting
  • Tec cooling and heating current limits can be set independently
  • Built in 2.5V high-precision reference source

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Constant temperature heating scheme

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Numerical control temperature adjustable refrigeration scheme

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The reverse end of the built-in operational amplifier 2 is directly connected with the output end to form a follower, and the in-phase end is controlled by DAC for temperature regulation. Built in operational amplifier 1 and external NTC are used for temperature measurement. The output signal of operational amplifier 1 is sent to ADC to form a temperature closed loop, which can realize digital PID to adjust the refrigeration temperature in real time.

3.2.2. Liquid level detection scheme

There are many liquid level detection methods, and the capacitance sensing method popular in the industry is selected in this scheme. The capacitance sensor AD7745 of ADI company is selected:

  • Built in 24 bit Σ-Δ Type ADC
  • Accuracy: 4 FF
  • Data update rate: 10 Hz to 90 Hz
  • I2C digital interface

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