Optical nanosensors called PEBBLEs (Probe Encapsulated By Biologically Localized Embedding) are nano-scale sensing devices that encapsulate analyte-specific dyes inside a biologically inert matrix for quantitative measurements inside cells. PEBBLEs come in four types of matrices and can be delivered into cells via four methods. They work by either directly measuring ions and small molecules using fluorescent indicators, or using ion correlation with a silent ionophore and chromoionophore to indicate changes in pH. PEBBLEs protect cells from dyes and dyes from cellular interference while enabling rapid, minimally invasive intracellular measurements of ions and molecules.

1. OPTICAL NANOSENSORS
Sensors with at least one of its
dimension in nanoscale
Designed for making quantitative
measurements in the intracellular
environment.

2. PEBBLE
 Probe Encapsulated By Biologically
Localized Embedding.
 PEBBLEs are nano-scale sensing devices which
encapsulate an analyte-specific dye and a
reference dye inside a biologically inert matrix
 These have been developed for several
analyte, including calcium, potassium.etc..

3. CLASSIFICATION
 PEBBLEs : four types - matrices
 four types - PEBBLE delivery into the cell.
 Two types - based of their working principles
 The four types of PEBBLE matrices commonly used are:
* Polyacrylamide(PAA)
* Sol-gel
* Polydecylmethacrylate (PDMA)
* Organically modified silicates

4. DELIVERY SYSTEMS
 Liposomal delivery
 Gene gun
 Picoinjection
 Phagocytosis

6. WORKING PRINCIPLE
(a) direct measurement PEBBLEs and
(b) ion correlation PEBBLEs.
a).....
* Sense ions and small molecules
* used for sensing H+, Ca2+, Mg2+,Zn2+ and
glucose.
* some analyte lack highly selective fluorescent
indicators.

8. b)....
 consists of a silent ionophores and a
chromoionophore bound together
 Silent-high affinity towards the ion of interest
 Chromo-fluorescent behaviour
 Due to a change in pH of the chromophore as
a result of the change in the H+
concentration, the fluorescent behaviour of
the chromophore is expressed

9. ION CO-RELATION

12. ADVANTAGES
 PEBBLE :protects the cell from the dye
 protects indicator dyes from cellular interference
 multiple dyes, ionophores, and other components
can be combined to create complex sensing schemes
 Minimal physical perturbation of the cell
 Small sensor size enables rapid measurement

13. Applications

Diagnosis and monitoring of diseases.
 Study early-embryo development
 Useful for quantitative measurements in
intracellular environment.
 Measure Zinc production and localization in
brain tissue.