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Characterization of SiN Integrated Optical Phased Arrays on a Wafer-Scale Test Station
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Measuring Bone Biomarker Alkaline Phosphatase with Wafer-Scale Nanowell Array Electrodes.

JuKyung Lee1,2, Cameron T Bubar1, Hi Gyu Moon2,3

  • 1Department of Mechanical and Industrial Engineering, College of Engineering , Northeastern University , Boston , Massachusetts 02115 , United States.

ACS Sensors
|November 22, 2018
PubMed
Summary

This study presents a novel electrochemical biosensor using a nanowell array (NWA) for detecting alkaline phosphatase (ALP), a bone formation marker. The highly sensitive NWA biosensor accurately measures ALP in small biological fluid samples, showing great potential for broad diagnostic applications.

Keywords:
alkaline phosphatase (ALP)bone formation indicatorelectrochemical impedance spectroscopy (EIS)immuno-affinity sensornanowell array (NWA)

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Area of Science:

  • Nanotechnology
  • Biosensor Development
  • Biomedical Engineering

Background:

  • Biosensors offer advantages over traditional assays by enabling analysis of small sample volumes.
  • Alkaline phosphatase (ALP) is a key serum indicator of bone formation, crucial for diagnosing bone-related conditions.
  • Existing methods for ALP detection can be limited by sample volume requirements, time, and cost.

Purpose of the Study:

  • To develop a highly sensitive electrochemical (EC) biosensor utilizing a nanowell array (NWA) for alkaline phosphatase (ALP) detection.
  • To evaluate the performance of the NWA biosensor for analyzing small volumes of biological fluids.
  • To demonstrate the potential of the developed biosensor for real-world applications in biomedical diagnostics.

Main Methods:

  • Fabrication of an EC biosensor with a nanowell array (NWA) electrode (2 × 1 mm², >10 million 400 nm diameter nanowells).
  • Immobilization and orientation of anti-ALP antibodies on the NWA surface using self-assembled monolayer and protein G.
  • Detection of ALP using electrochemical impedance spectroscopy (EIS) with a sample volume of 10 μL.
  • Calibration of impedance measurements against ALP concentration.

Main Results:

  • The NWA biosensor exhibited a wide linear dynamic range for ALP detection, from 1 pg/mL to 100 ng/mL.
  • A low limit of detection (LOD) of 12 pg/mL was achieved for ALP.
  • The sensor successfully measured ALP levels in real mouse serum samples from different age groups.
  • Results from the NWA biosensor correlated well with the standard photometric assay.

Conclusions:

  • The developed EC NWA biosensor demonstrates high sensitivity and a broad dynamic range for ALP detection.
  • The sensor's ability to analyze small biological fluid volumes highlights its potential for minimally invasive diagnostics.
  • This technology shows promise for developing advanced biosensors applicable to a wide range of biomedical analyses.