Case Study – World-Class Noise Performance

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.


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).


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.



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.

Case Study – IgG Detection

Case Study – IgG Detection

Case Study

Rapid Serological Testing for COVID-19 IgG

Test Platform

Delta Diagnostics introduces a platform that enables rapid and cost-effective development of new diagnostic tests. This platform can be employed to swiftly respond to the demand for a new test, such as in the case of emerging epidemics. Delta Diagnostics’ biosensor technology, based on photonic integrated circuits, enables quantitative and extremely sensitive multi-biomarker detection in small patient samples in a matter of minutes. 

Antibody Test

A rapid serological test for the detection of antibodies can be used to determine if a person has had an infection and potentially developed immunity. However, current point-of-care tests are limited in performance and not recommended to be used for individual patient diagnostics. 

As a technology showcase, Delta Diagnostics developed a rapid COVID-19 IgG test by immobilizing the Receptor Binding Domain (RBD) of SARS-CoV-2 on its proprietary optical chip. One of the great advantages of Delta Diagnostics’ platform is label-free detection, allowing to directly and quantitatively detect binding of biomolecules. This is shown in Figure 1, displaying the signals from different IgG monoclonal antibodies binding to the RBD-coated chip, where antibodies present in higher concentrations and/or with a higher affinity produce higher signals. 

Subsequently, the RBD-coated chip was challenged by a blind panel of 10 sera provided by Reinier Haga Medical Diagnostic Center (RHMDC). The samples were drawn from healthy individuals (pre-COVID-19 pandemic) and individuals with PCR-confirmed COVID-19. The PCR-confirmed sera were reference-tested at RHMDC using the Wantai total antibody test (WTA-test). The panel was sequentially analysed on Delta Diagnostics’ point-of-care development platform. Between consecutive sera, the chip was regenerated. This effective regeneration procedure allows for rapid testing without replacement of the chip. 

The time-to-result was less than 15 minutes per sample. 

Figure 1: Sensor signals for different validation samples containing different quantities and types of IgG antibodies. 

The unlocked panel data in Table 1, obtained after completion of the analysis, shows for each sample how many days after a positive PCR the serum sample was drawn, the WTA-test results for PCR-confirmed samples and the results obtained with the Delta Diagnostics test. 

Table 1: Blind panel test results for Delta Diagnostics’ test and the Wantai test. 

The panel consisted out of 5 sera drawn before the COVID-19 pandemic, classified as negative, and 5 sera of individuals with PCR-confirmed COVID-19, classified as positive. Results of all negatives and 4 out of 5 positives obtained with the Delta Diagnostics test matched the WTA laboratory test. Solely sample 9 tested negative at Delta Diagnostics, while the WTA-test was positive. This result is likely due to the fact that IgG antibodies are typically developed later than 8 days after onset of symptoms: The WTA-test is sensitive for all immunoglobulins, including IgM which is typically developed earlier, while the Delta Diagnostics test in this set-up specifically detects IgG.  

Next Steps

Currently available point-of-care antibody tests do not have the performance required for individual diagnostic use. As our chips carry multiple individually addressable sensors, it is relatively straight-forward to develop a test able to detect antibodies against different parts of the virus. Such multiplexed tests have been shown to be able to reach very high specificity. 

In addition, contrary to current point-of-care tests, our test provides quantitative information about the amount and/or quality of the antibodies, which allows monitoring of changes in a person’s immune status over time. 

Finally, the ability of our sensors to simultaneously detect different biomarkers would allow the development of a test that is sensitive to antibodies raised against different virus variants, potentially useful to determine with which variant the patient has been infected, or a test that can distinguish between different antibody types (IgG, IgA and IgM) providing more clinical information. 


We would like to thank the Reinier Haga Medical Diagnostics Center for providing the reference tested patient sera and our partner Covalab (FR) for providing the RBD and SARS-CoV-2 monoclonal antibodies used in this study. 

Case Study – SPR

Case Study – SPR

Case Study

Delta Diagnostics’ label-free biosensors match the performance of high-end SPR technology at a fraction of the cost

The Technology

An optical chip (photonic integrated circuit) is a small silicon chip with optical waveguides on the surface. Light is transported across the chip by these waveguides. Interaction of the light, through its evanescent field, with surface-bound molecules allows for quantitative detection of biomolecules.

By coating affinity molecules, such as antibodies, on the surface of the chip, Delta Diagnostics has developed an extremely sensitive label-free immunoassay platform. It is considerably less expensive than industry-standard Surface Plasmon Resonance (SPR) technology, making label-free biosensing more accessible.

Figure 1. Optical Chip

The Challenge

In order to benchmark our instrument with currently existing SPR biosensing instruments, we performed the same experiment on 3 systems: Delta Diagnostics’ prototype instrument and two commercially available high-end SPR systems. Figure 1 depicts the results obtained with the three systems.

As can be seen, very comparable results in term of amplitude and shape of the response were obtained with all three instruments, showing that the sensitivity of Delta Diagnostics’ instrument prototype matches that of commercially available systems in these first experiments.

Figure 2: Binding of IgG on a Prot A/G derivatized sensor for three different instruments. Sensors of each system were functionalized using a hydrogel matrix derivatized with recombinant Protein A/G, allowing straightforward preparation of various IgG-capture surfaces. All sensors were functionalized in the same process run to make sure that the coating was identical for each sensor. The same sample, consisting of 100 µg/ml pooled IgG in PBS, was applied to the 3 sensors.

Table 1 provides an overview of the measured performance in terms of the signal amplitude obtained at 15 minutes after the start of the measurement, the baseline drift and the noise (1σ). The signal amplitude and baseline drift are almost identical for all instruments. In terms of noise, the second SPR system performed slightly better than the Delta Diagnostics prototype instrument and the first SPR system.

Table 1. Comparison of the Delta Diagnostics prototype instrument with two commercially available SPR machines. Two numbers are given for the noise of the delta diagnostics instrument. This relates to the number of sensors on the chip. For this experiment, we used a chip carrying 5 sensors. These can be used individually or simultaneously. When the signals of all the sensors are averaged, the noise was 0.33 RU. When the sensors are used separately, resulting in more datapoints per measurement, the noise was 0.83 RU. Meanwhile, with an improved sensor design, Delta Diagnostics has been able to further reduce the baseline noise to 0.01 RU and expects to report a further reduction of at least a factor 2 in the near future.

Benefits of the Technology

From these first experimental results it can be concluded that Delta Diagnostics’ instrument matches the performance of commercially available SPR systems. In other areas, Delta Diagnostics outperforms currently available systems. These typically allow simultaneous detection of only one or a few interactions, where Delta Diagnostics allows the detection of up to 16 interactions simultaneously. Furthermore, due to the inherently inexpensive technology used, Delta Diagnostics will be able to provide instruments at a much lower price. The large number of sensors per chip will significantly lower the cost per data point.