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nMIS Dual Mode Sensors for Detection of Biomolecules

Microfluidics is the science and technology that deals with the flow of liquids from microliters (mL) to picoliters (pL) inside a micrometer sized channels1. The ability of microfluidics to miniaturize and mimic various laboratory procedures with limited space, great efficiency and low sample volumes these systems find use in various applications involving continuous flow microfluidics, droplet-based microfluidics, DNA chips (microarrays), molecular biology, etc.

A microfluidic chip is a set of microchannels molded into materials such as glass, silicon or polymers like polydimethyl siloxane (PDMS) 1.

Microfluidic platforms allow physicians to analyze a single drop of blood or urine sample for various markers of diseases without the need of sending comparatively large volumes of these samples to external laboratories for analysis2.

To determine a disease state, microfluidic sensors require specific disease-detecting biomolecules to be inserted into the platform of the system. These biomolecules are required to be well-bound to the sensor for them to remain in the sensor without being flushed by the incoming blood or urine sample2. As this process is time-consuming, there is an increasing interest in developing platforms with prepacked materials.

The development of such sensors is challenging as their development requires the device components to be subjected to conditions of high energy or ionized gas, which could cause difficulty for biomolecule survival2.

In an attempt to solve this problem, researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) have recently developed a novel sensor comprised of successfully sealed biomolecules, which is able to accurately detect the presence of markers that correspond to various diseases.

Researchers believe that these sensors present great use in healthcare diagnostics and pave path for new opportunities for production of new sensors utilizing such pre-packed microfluidic platforms for testing various biological samples such as blood and urine2.

Metal oxide semiconductor (MOS) sensors are comprised of three layers; a top conductive metal, such as gold, a middle insulator material, such as glass or silicon dioxide, and the bottom semiconductor layer, which can be made up of a material such as silicon3. This bottom silicon layer is sometimes deliberately adulterated with other substances to alter its conductivity by a process referred to as doping.

As a semiconductor, silicon has varying conductivities depending on the temperature and degree of doping it is exposed to3. The integration of MOS sensors into an electric circuit can occur as a result of the embedding of biomolecules onto an electrolyte-filled plastic well which is present on top of the sensor2,3. Biomolecules with different charges can be quantified by measuring the current that results from the application of certain voltage across the sensor2.

Amy Shen and her team at OIST have developed a novel sensor that is capable of measuring mass and charge in a similar manner to the traditional MOS sensors. This ability of the sensors to measure both mass and charge simultaneously is a great way to validate their results simply by switching from one mode to another and comparing the results 2.

The nanometal insulator semiconductor (nMIS) sensors designed by Shen’s team contain tiny gold metal island instead of the gold metal layer present in the MOS sensors2. The nMIS sensors have the potential to detect the mass of biomolecules by measuring the specific oscillating frequency of the surface electrons produced when light energy is supplied to them.

When biomolecules are added onto the nanoislands, the frequency of oscillation is directly proportional to the mass of the biomolecule2. Based on this principle, the sensors will be able to distinguish different biomolecules based on the frequency of oscillation that corresponds to a specific molecule.

In order to demonstrate the performance and stability of biomolecules on the nMIS sensor, Shen’s team studied the effect of oxygen plasma on immobilized biomolecules. The results showed that the nanoislands did not lose their functionality after exposure to low energy (<6000 J) oxygen plasma, which indicates that these sensors can be used in ready to use microfluidic immunoassay platforms, where immobilization of biomolecules is very important4.

Furthermore, interleukin-6 (IL-6) immunoassay studies were performed to validate the functionality of the nMIS sensors, and the results showed a shift in the localized surface plasmon resonance (LSPR) corresponding to the concentration of IL-64.

The nMIS dual mode sensor technology can be expanded to study other kinds of molecular binding events involving different molecules, such as aptamers, with different charges and masses4. The group of OIST researchers are hopeful that their newly developed sensor will make it possible for the detection of different diseases, while simultaneously incorporating several biomarkers in the same device to test for different diseases.


  1. “Microfluidics and Microfluidic Devices: A Review.” Elveflow. Web.
  2. “Sensor Sensation: Novel Sensor Capable of Measuring Both Charge, Mass of Biomolecules.” ScienceDaily. ScienceDaily, 22 Dec. 2016. Web.
  3. “Metal-Oxide Semiconductor.” National Tsing Hua University. 19 Dec. 2003. Web.
  4. Nikhil Bhalla, Doojin Lee, Shivani Sathish, Amy Q. Shen. Dual-mode refractive index and charge sensing to investigate complex surface chemistry on nanostructures.Nanoscale, 2017.
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