Nanobio Science

Nanobio Science


Improvement of sensitivity and accuracy by 100x through nanowell-array technology
Array of nano-sized wells (diameter=250nm) that allows control of individual molecular reactions

Nanowell : biomolecule immobilization and reation control (accuracy)

Array : signal amplification (sensitivity)

Uniform number : quantification of sensing signal (precision)

• The volume of each nanowell (250nm) is atto-liter (10-18liter)

• Total volume of nanowell-array electrode(9 x106) = 1 pico-liter(10-12L)

Development of accurate, highly sensitive, and small nanobiosensors that detect molecules from minute amounts of biological samples (blood, urine, sweet, etc)


H.Y.Lee et.al. Japanese Patents 3972096 (2008); 4324707 (2009); 4497903 (2009)

H.Y.Lee et.al JACS (2005), Langmuir (2005), Lab on a chip (2006), Appl.Phys.Lett. (2006), Advanced Materials (2008)–The Highlight, Small (2008)

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Advantages of Nanowell Array Sensor
Nanowell Array (NWA) electrode sesnor

  SEPARATION  

High signal-to-noise ratio

Structure close to the molecular level

• Significantly reduced background (or base) noise

• Signal can be amplified for statistical dependencies (ex : 1x107 times)

• Small sample required (> 1 pL)

• Sensitivity above the minimum pg level (> 1pg/ml) can be achieved

Conventional macro or micro electrode sensors

  AGGREGATION  

Low signal-to-noise ratio

• Big size difference between macromolecule and molecule

• High background (or base) noise

Sufficient sample required


It can be obtained high sensitivity through the control of reaction (1fM)

It can be measured quantitatively for the biomarkers of a very small amount (>1 picoliter)  


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Compared with conventional planar electrodes, Nanowell Array (NWA) reduces potential aggregation between molecules and spatially aligns biosprays, improving sensor sensitivity.


The combination of nanowell (NW) arrays structure leads to significant improvement of sensor sensitivity. Because it reduces potential aggregation and background noise from the electrode surface can be dramatically reduced, compared with conventional electrodes with flat surfaces. And the NW arrays have potentials to magnify signals for statistical reliability.


NWA structure provides 'high sensitivity' diagnostic by controlling chemical reactions in nanostructures that require small amounts of sample. Based on the advantages of NWA, we are opening a new era of digital healthcare using nanowell medical devices.


Combination of  NWA and electrochemistry for highly sensitive detection with small amount of sample

By combining nanowell arrays (NWAs) with electrochemistry, it becomes possible to achieve high-level biosensors, particularly in terms of sensitivity, limit of detection (LOD), multiplexing, and label-free diagnostics.

The nanowell array (NWA) structures, with diameters ranging from 50 to 240 nm, can theoretically detect target volumes at the attoliter level (10^-18 liters) per nanowell or approximately 8 femtoliters (10^-15 liters) per sensor. Therefore, the key technology lies in designing the geometry such that only one or a few biomolecules are immobilized in each nanowell.

Nano process technology


Development of nano size platform for rapid diagnosis / low cost production process

In order to use of biomedical nanotechnology, biocompatible and commercially available nanoprocess is essential In this sense, Mara Nanotech researchers have been working on biocompatible and commercialization of nanostructure by various nanolitho processes such as e-beam litho., focused ion beam, soft nanolitho., and nanoimprint litho. for EC nanowell array(NWA) electrodes.

Nanowell Arrays for Electrochemical Nanomedical Devices

Mass Production of Nanowell Sensors

1. Glass substrate size: 300 mm × 300 mm

2. Number of electrodes: 8

3. Working area: 0.7 mm x 0.7 mm

4. Working electrode: Gold

    Counter electrode: Platinum

    Reference electrode: Ag/AgCl

5. Electron beam deposition method

Gold surface layer (working electrode) thickness (2 types):

  • 140 nm
  • 490 nm

Through semiconductor technology, precisely controlled nanowell structures can be obtained. Additionally, because high-sensitivity and high-reproducibility label-free electrochemical nano-biosensors can be miniaturized, it is now possible to mass-produce nanowell sensors using nanolithography processes. To achieve this, the expertise lies in precisely controlling the biochemical reactions of molecules so that only a few biomolecules can be fixed within the nanowell.

Furthermore, advanced semiconductor nanoprocessing equipment is used for the commercial production of nanowell arrays (NWAs). Through these molecular immobilization and production process technologies, the time and cost required for commercializing research results can be reduced.