4.8 Article

Spearhead Nanometric Field-Effect Transistor Sensors for Single-Cell Analysis

Journal

ACS NANO
Volume 10, Issue 3, Pages 3214-3221

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b05211

Keywords

scanning probe microscopy; FET; biosensor; ATP; nanosensor; nanopipette; nanoelectrode

Funding

  1. Biotechnology and Biological Sciences Research Council [BB/L005816/1]
  2. Engineering and Physical Sciences Research Council [EP/1007482/1]
  3. Wellcome Trust [108429]
  4. Japan Science and Technology Agency PRESTO
  5. Graham Dixon Charitable Trust [WHCF_G00000]
  6. Deutsche Forschungsgemeinschaft [EXC1069]
  7. BBSRC [BB/M022080/1, BB/L005816/1] Funding Source: UKRI
  8. EPSRC [EP/I007482/1] Funding Source: UKRI
  9. Biotechnology and Biological Sciences Research Council [BB/M022080/1, BB/L005816/1] Funding Source: researchfish
  10. British Heart Foundation [RG/12/18/30088] Funding Source: researchfish
  11. Engineering and Physical Sciences Research Council [EP/I007482/1] Funding Source: researchfish
  12. Muscular Dystrophy UK [RA3/3050] Funding Source: researchfish
  13. National Institute for Health Research [NF-SI-0507-10267] Funding Source: researchfish

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Nanometric field-effect-transistor (FET) sensors are made on the tip of spear-shaped dual carbon nanoelectrodes derived from carbon deposition inside double-barrel nanopipettes. The easy fabrication route allows deposition of semiconductors or conducting polymers to comprise the transistor channel. A channel from electrodeposited poly pyrrole (PPy) exhibits high sensitivity toward pH changes. This property is exploited by immobilizing hexokinase on PPy nano-FETs to give rise to a selective ATP biosensor. Extracellular pH and ATP gradients are key biochemical constituents in the microenvironment of living cells; we monitor their real-time changes in relation to cancer cells and cardiomyocytes. The highly localized detection is possible because of the high aspect ratio and the spear-like design of the nano-FET probes. The accurately positioned nano-FET sensors can detect concentration gradients in three-dimensional space, identify biochemical properties of a single living cell, and after cell membrane penetration perform intracellular measurements.

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