Superhydrophobic lab-on-chip measures secretome protonation state and provides a personalized risk assessment of sporadic tumour

Abstract

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual’s diagnosis and/or help clarify risk in healthy populations.

Emerging Designs of Electronic Devices in Biomedicine

“…In both cases, data processing and analysis generate trajectories, the shapes of which are indicative of the time evolution and of the characteristics of the system (Figure 5f). SeOECT devices have been used to evaluate tumors [83]. Since cancerous states are associated with an altered protonation state of the intra/extracellular microenvironment, one can estimate the onset and progression of a cancerous disease from a measurement of the ionic content of a bloodderived cell culture.…”

“…Using data from the bio-chip and statistical techniques of analysis, we developed algorithms that segregated tumor patients from non-tumor patients. For the ~30 patients across two independent cohorts, the method identified tumor patients with high sensitivity and 93% specificity [83].…”

“…In cancer, the next generation of POC will probably be represented by 2-D material-based electrochemical biosensors/sensors [106] such as electrochemical apparatus [107], lateral flow assays (LFAs) [108], or paper-based colorimetric solutions [109]. The main biomarkers relevant in this field are nucleic acids such as mRNA and DNA; proteins such as antigens, enzymes, and peptides; some small molecules such as the reactive species of oxygen and nitrogen; and, notably, the protonation state [83]. Due to the chaotic nature of this medical condition, multiple marker solutions can fit the clinical needs better.…”

Microenvironment Molecular Profile Combining Glycation Adducts and Cytokines Patterns on Secretome of Short-term Blood-derived Cultures during Tumour Progression

“…Circulating tumour cells (CTCs) are cancer cells with a solid tumour origin recognized in the peripheral blood, their standard molecular definition is based on the positive detection of cells with an intact nucleus expressing cytokeratin (CK) but negative for CD45, a white blood cell (WBC) marker [ 4 ]. Moreover, we demonstrated that the secretome produced by cancer BDCs were superimposable to the intratumoral interstitial fluid extract from the primary lesion in the same patient for cytokines and glycan adducts content [ 5 , 6 , 7 ]. In this way, we analyzed here the secretome of BDCs focusing on the cytokines production and the advanced glycation products [ 7 ].…”

“…Moreover, we demonstrated that the secretome produced by cancer BDCs were superimposable to the intratumoral interstitial fluid extract from the primary lesion in the same patient for cytokines and glycan adducts content [ 5 , 6 , 7 ]. In this way, we analyzed here the secretome of BDCs focusing on the cytokines production and the advanced glycation products [ 7 ]. The analysis of the secretome of blood-derived cultures from cancer patients at different stages of the disease, provides a cross-section of knowledge of the molecules that alternate in production and secretion during the progressive steps of the disease.…”