Case Study – World-Class Noise Performance

Case Study

Delta Diagnostics’ world-class noise performance

In label-free biosensing, noise performance is critical. A low baseline noise level is a prerequisite to detecting analytes in very low concentrations and/or to detect low-molecular-weight analytes. Unfortunately, the noise performance of label-free biosensor instruments varies significantly between manufacturers. It can be anything between 0.01 Response units (RU) for the top-end instruments to several RU for lower-end instruments. In this case study, we have investigated the noise performance of Delta Diagnostics’ prototype instrument to assess how this compares to commercially available instruments.

Approach

Delta Diagnostics offers several types of chips that differentiate in the number of on-chip sensors and sensor type used. Generally speaking, ring resonator sensors have a slightly lower sensitivity, but their relatively small size allows a higher degree of multiplexing. Contrary, Mach-Zehnder interferometers can achieve a higher sensitivity but are also larger, limiting the multiplexablility. For this test, we used a chip that carries fourteen 3×3 Mach-Zehnder interferometers, allowing sensitive 14-plex detection. In addition, we used Delta Diagnostics’ proprietary signal processing to process the raw interferometer signals and evaluate the baseline noise. This signal processing was developed at Delta diagnostics with the specific aim to optimise noise performance.

In regular operation, binding the biomolecules to the biosensor surface causes a change in the optical refractive index at the immediate chip surface, which is subsequently detected. The detected refractive index change is proportional to the amount of surface-bound biomolecules. However, to exclude any noise contributions originating from biological processes, here we investigated baseline noise in an experiment where the sensor responds to a transition between two fluids having a slightly different refractive index.

Figure 1: Response for a transition from water to water with 3% IPA.

Figure 2: zoom-in on the curve in Figure 1 (top), and the deviation from a 2nd order polynomial fit (bottom).

Results

Figure 1 shows the response of a Delta Diagnostics’ sensor when transitioning from water to water with 3% isopropanol. A shift of over 2000 RU is observed. Subsequently, the noise was evaluated by zooming in on a particular part of the sensor response. The top graph in Figure 2 shows a zoom-in on the curve in Figure 1, with a 2nd-order polynomial fit. As can be seen, the number of data points amounts to ten per second. In other words, the sensor read-out is at 10Hz. Delta Diagnostics instrument allows read-out at 1 or 10Hz. The deviation from the fit is shown in the lower graph in Figure 2. The standard deviation from the fit is 0.01 RU per Square Root Hertz.

 

Conclusion

For 1Hz read-out, we achieve a baseline noise of 0.01 RU. This performance is only met by a select few top-end label-free biosensing instruments. Delta Diagnostics expects that further optimisation of its biosensors will lead to a further reduction in baseline noise and expect to report on a further reduction in baseline noise by at least a factor 2 in the near future.

Seed round from PhotonDelta & TNO Investment

News

Cash Infusion For Photonics-Focused Biosensor Startup Delta Diagnostics

Rotterdam-based Delta Diagnostics lands seed round from PhotonDelta & TNO Investment to help bring its biosensor system to the market faster.

14 July 2022, Rotterdam – Biosensor R&D start-up Delta Diagnostics has received a seed investment from two leading innovators: research organisation TNO – The Netherlands Organisation for Applied Scientific Research – and PhotonDelta, an ecosystem of photonic chip technology organisations. This investment enables Delta Diagnostics to further develop and validate its biosensor systems in preparation for a Series A investment round later this year.

A specialist in instrumentation for life science research and diagnostic test development, Delta Diagnostics, was spun out from TNO’s optics department in 2018 after a decade of research.

Typically, medical & life sciences instruments are very expensive and can only detect one or a few biomolecules at the same time. However, Delta Diagnostic’s biosensor technology uses photonic chips to detect up to 16 biomolecules simultaneously, with an instrument that is much more affordable.

Plans with the funding

Bart de Boer, CTO and co-founder of Delta Diagnostics, has firm plans for the seed funding: ‘’This investment enables us to further develop and validate our photonic biosensor system. The next step is to move from prototype to serial-producible product. We believe that our technology will ultimately result in new, more reliable, diagnostic tests that are developed at reduced time and cost.’’

TNO Technology Transfer Programme

Hans Boumans, director of technology transfer at TNO, was equally enthusiastic: “Delta Diagnostics is a great example of how TNO’s Technology Transfer Programme continues to accelerate market adoption. The startup’s ambition is a prime example of an organisation successfully delivering high tech that advances society, stimulates business and creates new jobs.”

Photonic chips for biosensing

As an ecosystem that researches, designs, develops, and manufactures solutions with integrated photonics technology, PhotonDelta provides funding to support startups like Delta Diagnostics, as Pieter Klinkert, Fund Manager at PhotonDelta, explains: ‘’We see great opportunities for biosensing instruments based on photonic chips, as the healthcare industry needs faster and cheaper solutions to diagnose patients. That’s why it makes sense that we support Delta Diagnostics in their next steps to validate and commercialise their products.’’

Currently, the international photonics market is worth € 7.3 billion euros with the Netherlands being a leading light in the technology’s development.

Delta Diagnostics’s technology is already being used at several universities and companies. As further funding is secured, the company’s aim is to build on this thriving customer base.

 

 

MIT R&D grant

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MIT R&D grant

Delta Diagnostics, together with project partner SensUR Health, obtained a MIT R&D grant from the Provincie Zuid-Holland for the development of a Chronic Kidney Disease test. This development will rely on a combination of the photonic biosensor technology of Delta Diagnostics and the Chronic Kidney Disease assays of SensUR Health to ultimately improve kidney patient care.

 

 

Instrument delivered to AUMC

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Instrument delivered to AUMC

Delta Diagnostics delivers a prototype R&D instrument to the Amsterdam University Medical Center, where the system will be used in the NWO-funded project “Profiling information using the chemical signature of a fingermark” in collaboration with the NFI, the National Police, The Police Academy, Merck Chemicals.

Proto Instrument Delivered

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Proto instrument delivered

Delta Delivers an instrument to the department Smart Sensor Systems of the Haagse Hogeschool. The Instrument will be used for the development of assays for various applications by both Physics students and Process and Food Technology students.