## 1 Introduction  
Improved diagnostics and treatment of aggressive cancer is one of the most challenging tasks in research today. The transformation from a normal cell into a tumor cell is a multistage process, typically involving progression from a pre-cancerous lesion to malignant tumors [1]. Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide, and the prognosis for patients with metastatic CRC (mCRC) is still poor [2]. The most common conventional method to culture cells today are monolayer 2D cell cultures, which are not accurately representing the cellular and micro-environmental interactions in vivo [3]. In vitro cultured 3D models of CRC have been shown to be valuable in drug discovery, drug resistance analysis, and studies of cell-cell and cell-matrix interactions that occur in the tumor microenvironment (TME) [4]. The development of safe and effective drugs is currently hampered by the poor predictive power of existing pre-clinical animal models that often lead to the failure of drug candidates in human trials [5]. sialic acid (SA) is a monosaccharide present on proteins and lipids on almost all cells, but are often deregulated on cancer cells and, therefore, of interest as a cancer-related target molecule [6]. Previous studies have shown the diagnostic relevance of molecularly imprinted polymers (MIPs) recognizing SA, so called SA-MIPs [7; 8; 9; 10]. MIPs are synthesized through a combination of functional monomers that strongly interact with a target molecule (template) and structural monomers and crosslinkers that covalently embed this complex in a polymer network [7; 11; 12]. The advantages of using MIPs include their low cost, quick preparation, chemical and physical stability, and reproducibility.  
The combination of MIPs loaded with a drug and a moiety targeting a membrane protein on cancer cells were shown by [PERSON] et al. [13]. Using a double-imprinting method, the authors showed that the nanoMIPs could not only target the membrane receptor but also selectively deliver the drug to the corresponding cells. For targeting cells without a consequent drug delivery system, it was important to confirm that the treated cells remained viable. SA-MIPs have been shown to interact with phagocytic cells in vitro without causing any inflammatory or toxic response [14]. Hence, the next step was to use SA-MIPs to target and detect spheroid cancer cells grown in in vivo-like conditions and investigate if the in vitro SA-MIPs spheroid system was physiologically relevant.  
SA would bind to the sialic acid-binding immunoglobulin-like lectin (Siglec), which provided a conserved mechanism for combatting pathogens [15]. The deregulation of SA and this pathway had been observed in diseases such as autoimmunity, neurodegeneration, allergy, and cancer. The importance of 3D in vitro systems and assays relied on the need to obtain reliable data regarding diagnostic tools and therapeutic candidates [16].  
In this study, we present a novel approach for targeting and detecting spheroid cancer cells grown in in vivo-like conditions. SA-MIPs were targeted to the CRC cell line HT29 as viable spheroid cultures in vitro without affecting the cell viability. We hereby propose the use of SA-MIPs as a non-toxic and valuable diagnostic tool for detecting cancer.