Recent years have seen intense appreciation for the heterogeneous and dynamic nature of solid tumours. Consequently, oncology has shifted from a ‘one-size-fits-all’ approach, towards the relatively tailor-made approach that is precision oncology. However, in order to realise the full potential of individualised treatment strategies, there is urgent need for sensitive, specific and precise methods of sampling tumour heterogeneity at the molecular level. Aptamers are small, single-stranded oligonucleotides which fold to form complex tertiary conformations as a result of intra-nucleotide binding. Aptamers are known as ‘chemical antibodies’ because they specifically bind their targets via an induced fit mechanism, in a similar manner to their conventional protein counterparts. In clinical diagnostics, aptamers represent a promising alternative to traditional antibodies due to their relatively small size, low cost synthesis, stability and minimal batch-to-batch variability. Furthermore, the ability to easily functionalise aptamers with reporter moieties in a 1:1 stoichiometric ratio confers greater benefits over traditional antibodies in terms of accurate quantitation. Using aptamers against the cancer stem cell-associated membrane proteins, EpCAM and CD133, we successfully utilised ‘aptahistochemistry’ to identify this highly invasive subpopulation of tumour cells by a chromogenic, sequential double-staining technique in FFPE colorectal carcinoma xenografts. Due to the potential for steric hindrance, similar techniques utilising traditional antibodies are not recommended for targets which are colocalised within the same cellular compartment. Having demonstrated the utility of our aptamers in discerning intratumoural heterogeneity in solid tissues, we then turned our attention towards less invasive ‘liquid biopsy’ methods for the detection of circulating tumour cells. Beginning with a traditional ELISA format for the isolation and quantification of EpCAM positive cells on an aptamer-functionalised microplate surface, we aimed to downscale this method from a laboratory setting to a portable, capillary-driven, 3D-printed microfluidic chip, which produces a chromogenic result that can be read by eye within 10-15 minutes. This would allow for real-time monitoring of disease progression and treatment responses to help make timely personalised treatment decisions.