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Second order nonlinear optical imaging of chiral crystals (SONICC) is a promising new method for the sensitive and selective detection of protein crystals. Relevant general principles of second harmonic generation, which underpins SONICC, are reviewed. Instrumentation and methods for SONICC measurements are described and critically assessed in terms of performance trade-offs. Potential origins of false-positives and false-negatives are also discussed.doi:10.1016/j.ymeth.2011.11.003 pmid:22101350 pmcid:PMC3264792 fatcat:npogr7ihjbh4bpnr6jcyudokei