Progress in our knowledge of tumor regulatory mechanisms and complexity led to the understanding of the physical parameters of cancer cells and their microenvironment, including the mechanical, thermal, and electrical properties, solid stress, and liquid pressure, as critical regulators of tumor progression and potential prognostic markers associated with clinical outcomes. The biological hallmarks of cancer and physical abnormalities of tumors are mutually reinforced, promoting a vicious cycle of tumor progression. A comprehensive analysis of the biological and physical tumor parameters is critical for developing more robust prognostic and diagnostic markers and for improving treatment efficiency. Like the biological tumor traits, physical tumor features are characterized by inter- and intratumoral heterogeneity. The dynamic changes of physical tumor properties during progression and as a result of tumor treatment highlight the necessity of their spatial and temporal analysis in clinical settings. This review focuses on the biological basis of the tumor-specific physical traits, the state-of-the-art methods of their analyses, and the perspective of clinical translation. The importance of tumor physical parameters for disease progression and therapy resistance, as well as current treatment strategies to monitor and target tumor physical traits in clinics, is highlighted.
Sensitivity of field‐effect transistor biosensors (BioFETs) for nucleic acid detection is often limited by weak electrostatic control and low probe density at the sensing interface. Here, we present a BioFET platform with improved sensitivity based on lightly p‐doped Schottky‐barrier silicon nanobelt transistors, exhibiting reproducible ambipolar behavior in a back‐gated configuration. These devices are encapsulated with an Al 2 O 3 /ZrO 2 nanolaminate to prevent device performance degradation and facilitate stable biofunctionalization. Dry‐state measurements demonstrate selective detection of prostate cancer biomarker, miR‐141, after immobilization of complementary capture DNA, achieving detection down to the ≈100 pM range, and discrimination against the non‐complementary sequence, miR‐155. To enhance sensitivity, template‐assisted self‐assembly of gold nanoparticles (AuNPs) is used to form ordered linear structures directly on the sensing region. The supracolloidal assembly of AuNPs at the sensing interface tunes the receptor spacing and orientation and amplifies the influence of target hybridization on transistor response. Compared to planar devices, the hybrid AuNP‐BioFET exhibits improved signal modulation while preserving the label‐free detection mechanism. This approach bridges scalable top‐down semiconductor technology and bottom‐up self‐assembled nanostructures, providing an innovative pathway for developing biosensing platforms with high sensitivity and multiplexing capabilities for detecting nucleic acids.
Sensitivity of field-effect transistor biosensors (BioFETs) for nucleic acid detection is often limited by weak electrostatic control and low probe density at the sensing interface. Here, we present a BioFET platform with improved sensitivity based on lightly p-doped Schottky-barrier silicon nanobelt transistors, exhibiting reproducible ambipolar behavior in a back-gated configuration. These devices are encapsulated with an Al2O3/ZrO2 nanolaminate to prevent device performance degradation and facilitate stable biofunctionalization. Dry-state measurements demonstrate selective detection of prostate cancer biomarker, miR-141, after immobilization of complementary capture DNA, achieving detection down to the ~100 pM range, and discrimination against the non-complementary sequence, miR-155. To enhance sensitivity, template-assisted self-assembly of gold nanoparticles (AuNPs) is used to form ordered linear structures directly on the sensing region. The supracolloidal assembly of AuNPs at the sensing interface tunes the receptor spacing and orientation and amplifies the influence of target hybridization on transistor response. Compared to planar devices, the hybrid AuNPBioFET exhibits improved signal modulation while preserving the label-free detection mechanism. This approach bridges scalable top-down semiconductor technology and bottomup self-assembled nanostructures, providing an innovative pathway for developing biosensing platforms with high sensitivity and multiplexing capabilities for detecting nucleic acids.
Impedance cytometry represents a technique that allows the electronic characterization of colloids and living cells in a highly miniaturized way. In contrast with impedance spectroscopy, the measurements are performed at a fixed frequency, providing real-time monitoring of the species traveling over the sensor. By measuring the electrical properties of particles in suspension, the dielectric characteristics (electric conductivity and capacitance) of both cells and particles can be readily determined. During the last years, this technique has been broadly investigated; however, it is still not trivial to differentiate particles of similar size based on their dielectric characteristics. A way to increase the discrimination abilities of this technique could be the integration of nanostructures into the impedance platforms. In this work, we present the impedance cytometry study of particles using microfluidic channels aligned over interdigitated gold nanowire structures as our impedimetric sensor. The characterization of particles of different sizes and their comparison with particles of different compositions will provide an understanding of the correlation between the electrical signal and the characteristics of each particle. This approach is an attractive element for label-free detection platforms that can be integrated into lab-on-a-chip systems and further implemented for single-cell analysis.