Screening


Moving forward with label-free technology


Label-free technology is gaining acceptance and opening doors for new drug discovery. Relatively new in the well-established world of high throughput screening (HTS), label-free technology provides opportunities for probing biomolecular interactions without spatial-interference, autofluorescent or quenching effects of labels. Endogenous targets and multi-component pathways can be explored in a cellular background that more closely reflect their natural environment. According to the recent report High Throughput Screening 2010: Effective Strategies, Innovative Technologies, and Use of Better Assays, based on interviews with 52 HTS directors at pharmaceutical companies and government-sponsored institutes, label-free technology adoption is reported to be one of the three most important trends that will impact HTS in the future.


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nterest in and use of label-free technology has increased in the past several years in drug dis- covery HTS labs. As compared to previously reported in our 2007 study, 42% versus 31% of the respondents are considering adopting the tech- nology now than in 2007 (Figure 1). According to the HTS report findings, cost of instruments and plates and low throughput are the most significant barriers to increased use of label- free technology (Table 1). These factors make it challenging to use label-free as a main screening technology for primary screening. Many directors who have label-free instruments do not use the tech- nology for primary screening of large-scale com- pound libraries, but instead for smaller screens, for example, fragment libraries with smaller numbers of compounds or hit-to-lead optimisation. In addition to cost and throughput, these directors indicate there is limited understanding of the phenotypic changes observed in cells using label-free technology


Drug Discovery World Winter 2010/11


and the sensitivity and the limits of detection for biomolecular interactions need improvement. Selected comments from respondents discussing their use and the limitations of label-free technolo- gy are shown below.


“We want to get away from fluorescence-based assays and some of the artifacts of these assays as well as the cost of labelling. The limitations of label-free technologies are that you see an affect in the phenotypic assay and then you need to try to correlate that to a biologic process. It works for GPCRs but it’s not always generalisable.” A non-commercial screening lab


“Yes, we are using label-free technologies but not for primary screening. We use them for hit verifi- cation and hit to lead optimisation, mainly because of the cost and throughput.”


A High Throughput Screening lab 41


By Dr Jennifer Hartigan, Cindy Liu and William Downey


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