03 Dec Miniaturization: how does it work?
(blog post header photo source: www.pixabay.com)
The progress of modern technologies has conditioned the development of new, multifunctional systems, which contain a large number of integrated functions. Multifunctional systems (mechanical, fluidic, electromechanical, thermal, etc.) are miniaturized in order to obtain portable multiple-use devices. In the 1980s, this research resulted in a new field known as MEMS (Micro-Electro-Mechanical Systems). With the development of this area, a variety of applications evolved in chemical, biological, and biomedical research when fluid manipulation led to the separation of a new discipline – microfluidics.
The subject of microfluidics is the manipulation of small amounts of liquid in one or more microchannels. Modern microfluidics grows into a Laboratory-On-Chip (LOC) concept because it integrates a large number of functions – from fluid mixing, particle separation, DNA amplification, use of biosensors to additional electronics, and detection optics. At the microscale, the physics of laminar flow enables prediction and precise manipulation in the microfluidic system. Small amounts of samples and reagents significantly reduce the costs, and therefore, microfluidics found an important application in Point-Of-Care Testing (POCT). POCT tests should work with the sample volume from millilitre to few microliters, be portable, and easy-to-use. Innovative scientific solutions are combining different materials and fabrication technologies with chemical and biological principles for providing reliable testing and detection, which can be done also by non-experts. The rapid testing and detection by POCT devices found the application in fields like healthcare, agriculture, and environmental monitoring.
A very important step in performing efficient microfluidic-based testing and POCT for that matter is the election of a suitable sample preparation method. In recent years, significant progress has been made in the field of sample preparation for miniaturized devices. To avoid potential errors and ensure reliable results, this initial part of the analysis must be precisely performed. Microfluidics and LOC technologies, also known as micro total analysis systems (μTAS), have proven to be suitable for this application. The most challenging aspect of minimal sample preparation is the risk of having a narrow array of tests that can be performed with such a sample.
In the context of nucleic acid (NA) testing methods associated with microfluidic devices, the pretreatment of complex samples usually involves extraction, purification, and preconcentration of target nucleic acid (DNA or RNA). The isolation of the intracellular component, such as DNA, typically requires the breakdown of the cell. The process leading to disruption of the cell membrane is called cell lysis. Cell lysis methods, utilized within miniaturized devices, can be classified based on the working mechanism: employment of mechanical forces, chemicals (buffers or enzymes), thermal or electrical energy for disruption of the cell membrane. Afterwards, nucleic acid needs to be purified and/or concentrated. Different NA extraction techniques as a part of the microfluidic device have been developed. These techniques are typically dealing with silica-based surface affinity, electrostatic interaction, nanoporous membrane filtration, or magnetic beads.
The ideal POCT could be developed by integrating a convenient microfluidic sample preparation system with a simple detection system, which would meet the requirements. World Health Organization (WHO) provides “ASSURED” guidelines for an ideal POCT – Affordable, Sensitive (avoiding false-negative results), Specific (avoiding false-positive results), User-friendly (easy to use with minimal training), Rapid & robust (enables treatment on the first visit), Equipment-free, and Delivered (accessible to end-users).
Adapted from Park, J., Han, D. H., & Park, J. K. (2020). Towards practical sample preparation in point-of-care testing: user-friendly microfluidic devices. Lab on a Chip, 20(7), 1191-1203. https://doi.org/10.1039/D0LC00047G
IPANEMA consortium member PhotonicSys developed miniaturized Surface Plasmon Resonance Sensor
PhotonicSys is a standalone detection system for real-time and accurate measurement of the Refractive Index (R.I/concentration) of fluids containing biochemicals. It works on the principle of Surface Plasmon Resonance in angular mode.
The signal obtained is translated into an accurate refractive index (and concentration) subjected to the precise calibration of the system. The system provides label-free detection of biomolecules in various assay formats (Direct, competitive, inhibition) depending upon the mode of functionalization of SPR sensor chips. It can be used for a broad range of applications, to name a few: Binding kinetics measurements and analysis, concentration measurements, free-label characterization of materials, and short (seconds) to long (days) duration dynamic processes. The present version (<50 mm, 1 kg) of the PhotonicSys SPR system can record sensorgrams with a detection limit down to 10-6 refractive index units (RIU) in a user-friendly graphical interface. The system also consists of 2 flow channels which can be placed physically on the sensor chip and used to handle fluids under flow. The channel dimension and volume are – 18 x 3.8 x 0.4 mm (W x H x L) and 27.36 μl respectively. Other technical specifications are as follows: the single power source of 110/230V, 50-60 Hz; installation requires Core 2 Duo 2.4 GHz or above, Windows 7 or above, 4 GB RAM, and USB port for communication. PhotonicSys provides various sensor chips depends upon the need for the application (e.g. for small molecule detection and whole-cell sensing).
Surface Plasmon Resonance Sensor from PhotonicSys is a portable device with user-friendly GUI. The flexibility of using a variety of substrates for different applications makes this device special. Apart from that, the integration of complex microfluidics and pumping systems also can be explored and be implemented without hassle.
Research and advances in the field of microfluidic-based POCT systems continuously growing. Great achievements have been done when considering the numbers of commercially available POCT devices. It has been forecasted that miniaturization could even revolutionize the market. It seems LOC devices will be part of our lives just like laptops or cell phones.
Is such a future close to us?!
Harpaz, D., Koh, B., Seet, R. C., Abdulhalim, I., & Tok, A. I. (2020). Functionalized silicon dioxide self-referenced plasmonic chip as point-of-care biosensor for stroke biomarkers NT-proBNP and S100β. Talanta, 212, 120792. https://doi.org/10.1016/j.talanta.2020.120792
Harpaz, D., Koh, B., Marks, R. S., Seet, R., Abdulhalim, I., & Tok, A. I. (2019). Point-of-Care surface plasmon resonance biosensor for stroke biomarkers NT-proBNP and S100β using a functionalized gold chip with specific antibody. Sensors, 19(11), 2533. https://doi.org/10.3390/s19112533