We have completed a challenging project that started with a referral from a partner. The liquid biopsy platform project was the design of a complex medical instrument and it required a combination of skills that we are known for: analog circuitry, FPGA, microprocessors, and firmware. The instrument is used for non-invasive liquid biopsies and requires the accurate measurement of a very low current in a sample of blood. These liquid biopsy devices can provide a simple and noninvasive method to diagnose cancer in the very early stages, which allows for more effective treatment and lower risk of mortality.
Sensing low currents
Our customer needed to measure a very wide current range: from 10 picoamps to 50 microamps. To measure these low currents accurately, our design had to have low leakage currents. Since leakage currents double every 10 degrees C, it is particularly difficult to make these sensitive current measurements in non-climate controlled environments. There wasn’t an off-the-shelf chip that could handle multiple channels of this type of measurement. So we used individual op amps, resistors and transistor switches with careful layout and grounding. Additionally, since leakage currents caused by assembly contamination can be a thousand times greater than the current we were trying to measure, it was critical to select the right PCB manufacturer and work with them to achieve ultra clean processing.
Good low-noise-design principles
Because noise from external sources was also a major challenge, proper shielding was important. Extreme care was needed to shield the incoming signals from external noise. The need for shielding and low leakage current required that every input channel be surrounded by a ground wire. This ground wire was carried all the way through the cables from one board to another board. We checked and reviewed the customer’s design for the board that interconnected through the cable, so that there wouldn’t be problems. The enclosure had to be carefully designed to provide shielding and to connect correctly to the ground of the circuit board. We reviewed the design of the enclosure to improve its shielding effectiveness.
To achieve the required accuracy, the circuit had to be calibrated. Self-calibration is done without any external equipment. It involves routing a known internal reference input to each channel of the board. The output is then read and compared to the expected value. Software stores the result and adjusts each reading to make it accurate. Calibrating small current measurements requires applying small currents, which is tricky, because the input switches introduce leakage and noise into the system. It took some very clever algorithms in software to overcome the shortcomings of the electronics. The self-calibration software was much more difficult than the actual measurement software.
Because the system needed to handle a wide range of input current from 10 picoamps to 50 microamps, we needed to automatically select different ranges. But more ranges increase the leakage current! So it was a careful balance in the design to handle all the circuit and software interactions to ensure accurate readings.
With 96 channels and over 3,000 components on the board, it was not a simple task. We were very happy that the first boards only had two jumper wires and only a few part values had to be changed. It is a real testament to the expertise of our engineering team and quality of their work that the first boards are in use in the client’s lab. They did an outstanding job.
The customer was very impressed with our project management where each week we reviewed the status of the schedule, the budget, and the technical risks, and what was coming up in the next few weeks, including the deliverables for each person on the team.
We were very effective in working with the customer in China, managing both the 15-hour difference in time zones and some language issues. None of our team spoke Cantonese. To help manage the language barrier we were careful in our calls to go through things slowly and carefully to make sure that we understood the customer and that we were being understood by them. We knew if we didn’t take the time to do that, we would have had serious problems. As it was, we had a great remote collaboration.