HOW IS CONTINUOUS MONITORING APPLIED?

Continuous monitoring sensors are applied for early warning and closed-loop control purposes. In early warning, the level of a signal is continuously monitored and action is taken when the level passes a threshold. Closed-loop control refers to continuous adaptations controlled by a continuous stream of measurement data.

HOW DO YOU COMPARE THE BPM SENSOR TO LAB-BASED TESTING AND TO OPTICAL SPECTROSCOPIES?

Laboratory-based testing (e.g. LC-MS, ELISA) is slow and is costly per test. Spectroscopic methods (e.g. NIR and Raman) are cost-effective per data point; however, for many analytes these methods are not sensitive and specific enough. The BPM technology opens a new solution space, for cases when lab testing is too slow and expensive, and when spectroscopies cannot deliver the required sensitivity and/or specificity.

SENSORS FOR CONTINUOUS GLUCOSE MONITORING ARE COMMERCIALLY AVAILABLE; WHY NOT YET FOR OTHER ANALYTES?

Commercial glucose sensors are based on enzyme-based electrochemical detection. This measurement principle is not generally applicable for the monitoring of other molecules such as proteins, peptides, small molecules, drugs, and nucleic acids. A new generic technology is needed, suited for a wide range of molecules and corresponding concentrations.

WHICH ANALYTES CAN BE MEASURED BY BPM?

The BPM technology has the potential to continuously measure all substances for which affinity binders can be developed, such as small molecules, hormones, drugs, peptides, proteins, and nucleic acids. We have performed proof-of-concept assays with aptamers, antibodies, and oligonucleotides as binders, demonstrating that analyte molecules can be detected in buffer and in filtered blood plasma, between picomolar and millimolar concentrations, using sandwich and competitive assay formats.

SINGLE MOLECULE RESOLUTION, WHY IS THAT RELEVANT?

Techniques with single-molecule resolution record digital signals from interactions between individual biomolecules. Statistical analysis of the data allows one to extract detailed characteristics, such as kinetic properties, distributions, different populations, and rare events. This information helps to achieve high sensitivity, specificity, precision, accuracy, and robustness.

WHAT WILL A BPM BIOSENSING SYSTEM LOOK LIKE?

A system for on-line monitoring will consist of an automated sample-taking system, automated sample processing (e.g. dilution and/or filtration), a disposable sensor cartridge, a reader system, and software for data interpretation. The processed sample fluid is guided through the sensor cartridge (containing the tethered BPM particles) and is collected in a liquid waste container. The reader instrument contains optical and electronic components for reading the mobility signals of the BPM particles. The mobility signals are mathematically processed, leading to actionable information for the end user.

HOW LONG CAN A BPM SENSOR BE USED?

The BPM sensing principle is reversible and does not consume or produce any reagents, so it is suited for continuous measurements over long durations. However, when a sensor is exposed to a fluid over long durations, components of the fluid can irreversibly stick to surfaces and particles, which can affect the sensor performance. The operational lifetime of a cartridge will depend on the composition of the fluid, the applied sample preprocessing, and the used anti-fouling coatings. We presently perform studies aiming for operational lifetimes on the order of days.

IS THE BPM BIOSENSING PRINCIPLE SUITED FOR MINIATURIZATION?

The individual particles of a BPM sensor yield sizable optical signals. This facilitates the miniaturization of the reader system. We expect that the BPM sensor system can become a wearable device in the future.

IS THE BPM TECHNOLOGY SUITED FOR MULTIPLEXING?

Multiplexing refers to the ability to measure multiple specific molecules in parallel, which is used to obtain comprehensive knowledge about biological systems and optimal diagnostic power in medical applications. A BPM biosensor consists of many particles that are individually resolved, so therefore the technology is suited for the measurement of multiple specific molecules in parallel.