How integrated optical receivers can meet the future needs of point-of-care testing instruments

How integrated optical receivers can meet the future needs of point-of-care testing instruments

Introduction

In vitro diagnostic (IVD) systems rely on optical receiver technology to obtain specific diagnostic results with high sensitivity. Mature technologies such as ELISA and PCR utilize fluorescent optical receiver chains to perform diagnostic tests. Likewise, point-of-care testing (PoC) also uses optical receivers as powerful tools to create accurate, flexible, and fast systems to obtain results. This article details the key factors to consider when designing an optical PoC receive chain, explaining why an integrated optical front-end can meet these performance requirements and the corresponding key advantages - helping to build a platform that can adapt to future needs.

Basic knowledge of fluorescence detection and diagnostic technology

Fluorescence-based IVD detection uses light of a specific wavelength to excite a sample containing a fluorescent label, as shown by the green arrow in Figure 1. If the sample contains the target analyte, the fluorescently labeled target analyte emits low-energy light in response to excitation. For example, in Figure 1, the fluorescent label in the sample emits red light in response. This emitted light is the fluorescent signal we need to detect to determine whether the sample contains the target analyte and its content.

Figure 1. IVD fluorescence detection system.

Diagnostic tests based on fluorescence methods require a threshold to detect fluorescence. If the received fluorescence signal is below the threshold level, it cannot be determined that the target analyte is present in the sample. Electronics and other factors in the system may create background noise that increases the threshold. To lower threshold levels while consistently achieving better sensitivity without sacrificing selectivity, we need to carefully design the optical detection system to ensure that the signal chain does not increase the level of background noise.

Typical PoC fluorescence detection system

A typical PoC diagnostic fluorescence detection system uses a light-emitting diode (LED) to generate excitation light and a photodiode (PD) to detect the fluorescence emitted by the sample. PD generates a current that is proportional to the intensity of the fluorescent signal. PD currents are usually very low compared to the noise floor, so electronic systems need to be carefully designed to achieve high-sensitivity detection without sacrificing selectivity. Figure 2 shows the main components of a typical PoC fluorescence detection system. The transimpedance amplifier (TIA) converts the current signal of the PD into a voltage signal, and the analog-to-digital converter (ADC) digitizes the voltage signal and converts it into the corresponding fluorescence level.

Figure 2. Typical PoC diagnostic fluorescence detection system.

Performance requirements of PoC fluorescence detection system

Designers of PoC systems need to try to achieve the highest diagnostic sensitivity without sacrificing selectivity. This requires PoC instrumentation to reliably identify very low PD currents in response to LED excitation. For example, a highly sensitive system must be able to detect picoamp-level PD currents in response to LED excitation currents in the 100 mA level. That is, the system must be able to detect PD current with approximately 140 dB optical attenuation.

Achieving these capabilities requires a variety of device-level and system-level design considerations. The design of the analog front end (AFE) of PD is particularly important. Because PD currents are typically very weak compared to the noise floor, the TIA must have high gain and low input bias current. In addition, there are other important parameters that need to be considered, including low TIA input offset voltage, and the minimum distance between the PD and TIA.

System design is also an important factor in achieving high-sensitivity detection. Fluorescence detection must be synchronized with LED excitation, so the system requires a controller to ensure this synchronization. To identify weak PD current signals among the noise floor, the system usually needs to calculate the average of multiple fluorescence readings. This averaging technique is an important function of the controller. The drift of ambient light and LED will cause system errors. If the controller can be used to suppress ambient light and suppress LED drift, the overall advantage of system performance can be achieved.

Advantages of Integrated Optical Front-End Receiver

There are two distinct architecture options for the signal chain of a PoC reader: a completely discrete solution (shown in Figure 2), or the use of an integrated optical front-end (shown in Figure 3).

Figure 3. PoC inspection system using integrated optical front-end.

The first obvious advantage of an integrated solution is that it helps simplify system design. Integrated solutions enable synchronization of fluorescence detection and LED excitation within the optical front-end. Using an integrated optical front-end also reduces peripheral components and enables a more compact solution, thereby reducing the size of the device while reducing BOM and power management complexity. Another very critical point is that the integrated optical front-end can configure parameters such as photodiodes, LED drivers and filters through firmware, while discrete solutions cannot provide this configurability and require new hardware to be developed. Configurability is critical because we need to adjust the platform at any time based on changes to improve or adopt new detection methods. This is because new variants of some pathogens and some new diseases are constantly emerging, so it will be a big advantage to build a receiver platform that can implement new detection methods without changing the hardware.

Integrated optical front-ends have clear advantages, but measuring the performance of optical front-ends in low-light fluorescence applications is not straightforward. Simply considering the signal-to-noise ratio (SNR) of an integrated optical front-end does not reveal the true performance of the optical receiver. This is because light levels are often very low, so the absolute noise floor of the optical front-end, not the SNR, is the critical parameter. Although the 1/f noise component will limit the improvement of the noise floor by the averaging method, we can still use the averaging method to reduce the noise floor based on the time scale of the fluorescence measurement. Therefore, absolute dark current noise, especially flicker noise, is a major consideration. Many data sheets for integrated optical AFEs do not give the dark current noise of the entire system (including PD), so we need to measure this value separately.

Integrated Optical Front End from Analog Devices

ADI's integrated optical front-ends, such as the MAX86171, are ideal for PoC fluorescence applications and can integrate the analog signal chain and digital controller to form a single-IC solution for optical receivers. The MAX86171 includes an adjustable photodiode input, a 19-bit ADC, a low-noise LED driver, and a FIFO-buffered serial interface.

Figure 4. Functional block diagram of the MAX86171.

With 9 LED channels and 4 PD channels, this AFE has enough channels to support multiple detection methods and support future detection expansion without the need for hardware upgrades. The device is programmable via SPI or I2C, allowing fine-tuning of parameters such as integration time, mean range and dynamic range. The FIFO enables measurements to be taken while the MCU is in sleep mode, extending the battery life of handheld PoC systems.

More importantly, the device has high performance and low noise characteristics, which can help build high-sensitivity detection systems. Thanks to the averaging function and low 1/f noise, a signal chain consisting of a 7.5 mm2 photodiode has a dark current noise of only 11 pA rms, enabling reliable detection of low photodiode currents in the range of 1 pA to 10 pA, especially Ideal for low-light fluorescence applications. In addition, the device's excellent PSRR and ambient light rejection characteristics relieve system engineers from the burden of designing power supplies and mechanical enclosures.

Figure 5. Low-light measurements using the MAX86171.

We use the MAX86171 to drive an LED through a multilayer neutral density (ND) optical filter and then receive it through a photodiode to verify performance, as shown in Figure 5. By increasing the density of the ND filter, the optical attenuation can be varied from 40 dB (ND2) to 140 dB (ND7), thereby simulating the reduction in fluorescence content during PCR or LAMP detection. The MAX86171 can reliably detect photodiode currents above background dark current with better than 10 pA resolution at attenuation below 140 dB. The MAX86171's high sensitivity is due to the low dark current noise of only 11 pA rms when the photodiode is connected to the optical front-end.

Figure 6. MAX86171 performance.

After measurement, it was found that the performance of MAX86171 exceeded the performance requirements of PoC instruments and was fully suitable for the detection of various biochemical target analytes. The MAX86171's internal registers support firmware settings such as pulse width, pulse intensity, gain, and offset. In addition, the MAX86171 supports options such as filtering, averaging, and ambient light rejection to optimize optical detection performance. In summary, the MAX86171 is an extremely sensitive solution that can support new detection methods without changing the hardware.

in conclusion

The circuit design of the IVD system requires careful consideration to ensure high sensitivity detection without sacrificing selectivity. The most critical thing for a detection system adapted to various biochemical target analytes is to ensure that it can identify various weak electronic signals. Only in this way can accurate diagnostic results be provided.