Affinity imaging mass spectrometry (AIMS): high-throughput screening for specific small molecule interactions with frozen tissue sections

A novel screening system, using affinity imaging mass spectrometry (AIMS), has been developed to identify protein aggregates or organ structures in unfixed human tissue. Frozen tissue sections are positioned on small (millimetre-scale) stainless steel chips and incubated with an extensive library of...

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Bibliographic Details
Published in:Analyst (London) 2015-11, Vol.140 (21), p.7202-7208
Main Authors: Yoshimi, T, Kawabata, S, Taira, S, Okuno, A, Mikawa, R, Murayama, S, Tanaka, K, Takikawa, O
Format: Article
Language:English
Subjects:
Affinity
Agglomeration
Alzheimer Disease - drug therapy
Amyloid beta-Peptides - chemistry
Antibodies - chemistry
Biomarkers - chemistry
Brain
Brain - drug effects
Brain - metabolism
Cryopreservation
Equipment Design
Freezing
Frontal Lobe - metabolism
Frozen
Humans
Imaging
Ions
Mass spectrometry
Mass Spectrometry - methods
Oxygen - chemistry
Phosphorylation
Robotics
Screening
Stereoisomerism
tau Proteins - chemistry
Technology, Pharmaceutical - methods
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Summary:A novel screening system, using affinity imaging mass spectrometry (AIMS), has been developed to identify protein aggregates or organ structures in unfixed human tissue. Frozen tissue sections are positioned on small (millimetre-scale) stainless steel chips and incubated with an extensive library of small molecules. Candidate molecules showing specific affinity for the tissue section are identified by imaging mass spectrometry (IMS). As an example application, we screened over a thousand compounds against Alzheimer's disease (AD) brain tissue and identified several compounds with high affinity for AD brain sections containing tau deposits compared to age-matched controls. It should also be possible to use AIMS to isolate chemical compounds with affinity for tissue structures or components that have been extensively modified by events such as oxidation, phosphorylation, acetylation, aggregation, racemization or truncation, for example, due to aging. It may also be applicable to biomarker screening programs.
ISSN:0003-2654
1364-5528
DOI:10.1039/c5an01381j