Dendritic Chain Reaction

Abstract

Signal amplification techniques are broadly used to improve the detection sensitivity of various analytes for diagnostic purposes. We have developed a novel, non-PCR-based modular technique for exponential amplification of diagnostic signals that is conveniently performed in an aqueous environment. The technique is based on a distinctive dendritic chain reaction (DCR); the diagnostic signal is generated upon disassembly of a self-immolative dendrimer that releases chromogenic molecules. Under ideal conditions, a single analyte molecule initiates a DCR that generates a strong diagnostic signal. When coupled with a protease diagnostic probe, the DCR technique detected the activity of penicillin-G-amidase with high sensitivity. This is the first example of exponential signal amplification performed under aqueous conditions that is not based on PCR.

Modular theranostic prodrug based on a FRET-activated self-immolative linker

“…We and others [18,19] have developed various molecules with self-immolative capabilities including linear linkers, dendrimers and polymers [20][21][22]. These self-immolative compounds have found application in prodrug design [10,23], targeted drug delivery systems [7,24], diagnostic probes [25] and signal amplification techniques [26][27][28][29][30]. In this study, we used a distinctive self-immolative linker to connect a specific substrate to a chemotherapeutic drug.…”

Dendritic chain reaction: Responsive release of hydrogen peroxide upon generation and enzymatic oxidation of methanol

“…When the same experiment was performed with DCR probe 2, the observed signal was only 53-fold stronger than that obtained by a classic probe. 11 In order to obtain an ideal DCR probe, one should design a molecule that is highly stable to spontaneous hydrolysis but yet can undergo rapid disassembly upon relation with the analyte. The higher stability of the current probe reduces to some extent its rate of disassembly.…”

“…2,3 Recently, we introduced a new technique for signal amplification 4,5 that can be used in diagnostic detection of analytes [6][7][8][9][10] , which is based on a distinctive dendritic chain reaction (DCR). 11 This technique depends on the disassembly properties of a self-immolative dendrimer 12,13 to generate an exponential evolution of a diagnostic signal. The analyte of interest reacts with the trigger of the DCR probe to release a reporter unit and reagents.…”

Autoinductive Exponential Signal Amplification: A Diagnostic Probe for Direct Detection of Fluoride

“…Recently, several groups, including ours, have reported new approaches for signal amplification on the basis of the exponential progress of chemical reactions of small molecules. [2][3][4][5][6][7][8][9][10] We have introduced a novel modular technique for the exponential amplification of a diagnostic signal: amplification is achieved through a distinctive dendritic chain reaction (DCR), [11] which is generated by the disassembly of self-immolative dendrimers. [12,13] A single activation event initiated by the analyte of interest leads to a chain reaction that results in complete disassembly of all the probe molecules through an exponential progress to ultimately release many copies of dye molecules.…”