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In this study, the growth of Escherichia coli was monitored using a complementary metal-oxide-semiconductor (CMOS) near-field sensor array. Each of the 1488 integrated elements, arranged in a 3 mm square, has a resonator that oscillates at 65 GHz. The effective capacitance of the resonator is altered by changes in the dielectric properties of the sensor surface, which shifts the resonance frequency. Growth curves of E. coli at different initial concentrations (OD600 = 0.01, 0.03, and 0.05) were monitored. A suspension with initial turbidity of OD600 = 0.05 was cultured in a medium, and the sensor successfully distinguished between viable E. coli and heat-treated dead E. coli in 20 min. Moreover, the apparent suppression of growth was observed in the presence of 500 μg/mL streptomycin. As the sensor is composed of arrayed elements, and the area of sensitivity distribution of the element is larger than the size of one bacteria, the variation in the output value of each element may reflect the number and movement of bacteria. This study revealed that the presence of viable E. coli could be rapidly confirmed by using the change in permittivity caused by the displacement of media by E. coli near the sensor surface.

In this paper, we demonstrated parallelized detection of fluorescent microbeads flowing in multiple microfluidic channels coupled with an array of single photon avalanche diodes (SPADs). A complementary metal-oxide-semiconductor (CMOS)-integrated circuit (IC) containing an SPAD array was used for time-domain separation of fluorescence photons from excitation photons using fast gating and active quenching circuits to realize parallelized detection of fluorescence signals without complex microscopy and optical filters. The system can be used for the development of a parallelized flow cytometry system.

In this paper, a CMOS biosensor integrated circuit (IC) focusing on dielectric relaxations of biological water with 120 and 60 GHz oscillator arrays is proposed. To realize label-free biosensing, we focus on frequencies around 100 GHz where changes in the dielectric constant of water become prominent as many a water molecule is bound to biomolecules. To detect the state of the biological water, sensing elements based on LC-oscillators operating at 120 and 60 GHz are realized using the 65 nm CMOS process. The sizes of the sensing elements are significantly smaller than the wavelengths of the operating frequencies, therefore 2-D arrays can be implemented in a chip. The trial chip enables us to obtain spatial distributions of the targets. In this paper, the cultivated bacterial colony growth is monitored and other biosensing applications are explained, which showcase possibilities for using the biosensor IC.

The water present in the close vicinity of biomolecules is particularly relevant to the function of the biomolecules and is termed “biological water” in contrast to ordinary “bulk water” that fills the region beyond this vicinity (Fig. 28.3.1). Many studies have revealed that these two types of water exhibit clear differences in their dielectric relaxations. First, bulk water has two major relaxation modes: (i) the first mode represents the dielectric relaxation of the cooperative organization of hydrogen-bonded water molecules with a time constant td (≈8ps), and (ii) the second mode exhibits a faster relaxation time constant tf (≈0.27ps) and is usually attributed to the rotation of the water molecules that are not involved in hydrogen bonding. On the other hand, a slower relaxation (ts) appears in biological water because of “bound water” that is strongly bonded to biomolecules and less movable compared with bulk water. Owing to the presence of ts-mode water, the fractions of td- and tf-mode waters in biological water are smaller than those in bulk water. In this manner, the existence and status of biological water is reflected in the complex dielectric constant at a frequency around 100GHz. Because the ionic polarization of electrolytes (e.g., Na, K, Ca) strongly affects the dielectric loss in the frequency range lower than 50GHz, a difficulty arises in differentiating the dielectric relaxations of water from that of the ionic polarization [2]. By limiting the observation frequency to higher than 50GHz, we can eliminate this difficulty. By focusing on the dielectric relaxations of biological water, we present a CMOS biosensor IC that can detect and visualize the target biomolecules by using biological water as a label.