Local reaction fields on a CMOS sensor array utilizing a magneto-Archimedes levitation–based magnetic particle-arrangement method

Highlights

• Electrodes in CMOS biosensor arrays detect pathogens and other microparticles.

• Their molecular-recognition-element reaction fields should have the same size.

• A fast accurate, compact particle-arrangement method of ensuring this is proposed.

• It uses a particle magnetic-adsorption mechanism and magneto-Archimedes levitation.

Abstract

Rapid on-site identification of pathogenic microorganisms is necessary to minimize the spread of infection. In this study, a magnetic particle-arrangement technology based on magneto-Archimedes levitation is proposed to address this need. The effectiveness of the proposed method has been verified on a complementary metal oxide semiconductor (CMOS) sensor array implementing a particle magnetic-adsorption mechanism utilizing microelectromechanical systems (MEMS) process technology. A medium with highly adjusted K₃[Fe(CN)₆] concentration (0.2 mol/l) is poured over the CMOS sensor array surface after polystyrene microparticles (diameter: 25 μm) were distributed on it, causing one microparticle adsorbed on each channel to remain fixed in place while the remaining microparticles float in the surrounding medium; the magnetic and gravitational forces act on the microparticles distributed outside the channel in such a way that increasing the concentration of the K₃[Fe(CN)₆] surrounding medium changes the total force direction acting on the microparticles from downward to upward. These results show that the MEMS mechanism on the sensor is highly accurate, achieving 99.6 % accuracy in particle arrangement. Thus, a local molecular-recognition-element reaction field of uniform size was formed in most of 4096 channels of the CMOS sensor array by implementing a magnetic particle-arrangement method incorporating magneto-Archimedes levitation.

Introduction

Portable biosensor devices are expected to be extensively used for various kinds of on-site screening, such as testing for pathogenic microorganisms (bacteria [[1], [2], [3]], viruses [[4], [5], [6], [7], [8]], and parasites [9]) to control the spread of infections; home testing of patients in home health management (for glucose [10,11], uric acid [10], cholesterol [10], albumin, [12], troponin [13], and cortisol [14]); and field testing of environmental substances (agricultural products and related substances [[15], [16], [17]], heavy metals [[18], [19], [20]], and toxins [21,22]). It is thus reasonable to anticipate a continually expanding market for portable biosensor devices [14]. The prerequisites of an efficient portable biosensor device for rapid on-site screening are high sensitivity, short processing time, and compactness. In the quest for an efficient portable biosensor, several types of detection methods have recently been studied and developed, including electrochemical (field-effect transistor [7,8,13,23] and electrochemical impedance spectroscopy [14,24]); optical (surface plasmon resonance [3,6,19,[25], [26], [27]] and fluorescence [5,22,28,29]); magnetic (nuclear magnetic resonance [1], magnetoelastic [12], and magnetoresistive [30]); quartz crystal microbalance [31]; and surface acoustic wave [4] methods. In this study, the focus is on the fabrication of biosensors using complementary metal oxide semiconductor (CMOS) integrated circuits (ICs). This research is still at an early stage, and important sensor-performance metrics have not yet been obtained. An important step in this direction would be the standardization of the size of the local molecular-recognition-element reaction field, the focus of this paper.

Because CMOS biosensors detect electrons directly without using a transducer such as a phototransistor, measurement can be carried out easily and quickly. It is possible to measure multiple items simultaneously by integrating the sensors, and mass production methods are available to reduce costs. Currently, redox-potential detection using an extended gate expected to have high accuracy is being actively developed [[32], [33], [34]]. In addition, enzyme-immobilized microparticles have been tested as local reaction fields for the molecular-recognition element of the sensor, reducing cost and consumption of the enzyme and localizing the field in the vicinity of the electrode [35]. Because the microparticles are randomly distributed on the sensor array, the sensor-array electrodes have reaction fields of different sizes, which contributes to variation in sensor sensitivity. To overcome this challenge, an attempt was made to arrange microparticles on the channels of a sensor array so that the sensor-array electrodes would have reaction fields of the same size. In this way, it would be possible to align the detection signals of the channels and thus improve the sensor sensitivity.

Utilizing a modulated magnetic field to adsorb diamagnetic particles is one effective method for arranging several particles in a non-contact and non-destructive manner [36]. A magnetic particle-arrangement mechanism that can be implemented on ICs was successfully developed previously [37]. In this study, the same mechanism has been implemented on a CMOS sensor array utilizing microelectromechanical systems (MEMS) process technology. It was necessary to improve the arrangement accuracy by indicating the predetermined position in which each particle was intended to be arranged and removing excess particles distributed anywhere else [37]. Therefore, to increase the proportion of one-particle-per-channel arrangements that include the sensor-array electrode, the provision of a trench structure to the channel and the use of magneto-Archimedes levitation were investigated. The purpose of this study is to implement a magnetic particle-arrangement mechanism on the CMOS sensor array and to improve the particle-arrangement accuracy.