HOW CAN CONTINUOUS BIOMOLECULAR MONITORING BE APPLIED?
Continuous biomolecular monitoring can be applied for early warning and closed-loop control purposes. In early warning, the level of an analyte (= a molecule of interest) is continuously monitored and action is taken when the level passes a threshold. Closed-loop control refers to continuous adaptations controlled by a continuous data input. These functionalities are interesting for real-time biological studies, patient care, and industrial and environmental monitoring.
CONTINUOUS BIOCHEMICAL MONITORING IS ALREADY COMMERCIALLY AVAILABLE FOR GLUCOSE, WHY NOT YET FOR OTHER ANALYTES?
Sensors for continuous glucose monitoring (CGM) are commercially available from several companies. However, the underlying sensing principle (enzyme-based electrochemical detection) is not generally applicable for the monitoring of other molecules, such as proteins, peptides, small molecules, drugs, and nucleic acids. New generic technologies are needed that are suited for a wide range of molecules and molecular concentrations.
SINGLE MOLECULE RESOLUTION, WHY IS THAT IMPORTANT?
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.
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 formats.
WHAT COULD A BPM BIOSENSING SYSTEM LOOK LIKE?
A biosensing system consists of a reader instrument, a disposable sensor cartridge, and an interfacing system that connects the sensor to a biological system under study. The interfacing system could for example be a microdialysis probe that generates a fluid stream with analyte molecules. The fluid stream flows through the sensor cartridge, which contains the tethered BPM particles. The reader instrument contains optical and electronic components for reading the mobility signals of the BPM particles. The mobility signals are mathematically processed in order to lead to output information that is meaningful for the user, e.g. a curve of analyte concentration as a function of time.
HOW LONG CAN A BIOSENSOR CARTRIDGE 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. Such changes can be reduced by applying anti-fouling coatings and sample preprocessing. For the moment, we aim to develop sensor cartridges that can continuously operate for 24 hours without interruption.
IS THE BPM BIOSENSING PRINCIPLE SUITED FOR MINIATURIZATION?
The individual BPM sensor particles yield sizable optical signals, which facilitates the miniaturization of the reader instrument. In the future, we expect that the sensors can become so small that they may even be suited for on-body applications.
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.
YOU PUBLISH SCIENTIFIC PAPERS AND FILE PATENT APPLICATIONS; WHY EXACTLY?
Groundbreaking innovations need a solid scientific foundation. We write scientific articles in order to demonstrate high quality standards, and publishing helps to connect to academic and industrial communities. We file patent applications in order to gain rights to bring innovative products to the market.