Marek Sternheim

Towards toxicity detection using a lab-on-chip based on the integration of MOEMS and whole-cell sensors

A lab-on-chip consisting of a unique integration of whole-cell sensors, a MOEMS (Micro-Opto-Electro-Mechanical-System) modulator, and solid-state photo-detectors was implemented for the first time. Whole-cell sensors were genetically engineered to express a bioluminescent reporter (lux) as a function of the lac promoter. The MOEMS modulator was designed to overcome the inherent low frequency noise of solid-state photo-detectors by means of a previously reported modulation technique, named IHOS (Integrated Heterodyne Optical System). The bio-reporter signals were modulated prior to photo-detection, increasing the SNR of solid-state photo-detectors at least by three orders of magnitude. Experiments were performed using isopropyl-beta-d-thiogalactopyranoside (IPTG) as a preliminary step towards testing environmental toxicity. The inducer was used to trigger the expression response of the whole-cell sensors testing the sensitivity of the lab-on-chip. Low intensity bio-reporter optical signals were measured after the whole-cell sensors were exposed to IPTG concentrations of 0.1, 0.05, and 0.02mM. The experimental results reveal the potential of this technology for future implementation as an inexpensive massive method for rapid environmental toxicity detection.

Bioluminescence Detection Using a Novel MEMS Modulation Technique

A novel modulation microelectromechanical systems (MEMS) technique is introduced to overcome the low-frequency (flicker) noise of photodiodes. The transmissive shutter is placed as an add-on device between an optical source and a photodiode, and is implemented as a method to enhance the signal-to-noise ratio, adapted for the detection of low-intensity bioluminescence. The detection of the signal below the noise level of photodetector is demonstrated by implementing a lock-in amplifier that registers the modulated signal at four times the frequency of the electrical excitation signal of the modulator. This work represents the first reported attempt to use a MEMS modulation technique for the detection of low-intensity signals

Integrated Heterodyne MOEMS for detection of low intensity signals

A novel MEMS-based modulation scheme is presented as a method to enhance the signal-to-noise ratio (SNR) of silicon photodiodes adapted for the detection of light-emitting bio-reporter signals. Photodiodes are an attractive photodetector choice because they are VLSI compatible, easily miniaturized, highly scalable, and inexpensive. Silicon photodiodes exhibit a wide response range extending from the ultraviolet (UV) to the near infrared (IR) part of the spectrum, which in principle is appropriate for sensing low intensity optical signals. Silicon photodiodes, however, exhibit limited sensitivity to optical dc signals, as the magnitude of the low frequency noise is comparable to signal magnitude. Optical modulation prior to photodetection overcomes the inherent low frequency noise of photodetectors and system detection circuits. The enhancement scheme is based on a design of high frequency optical modulators that operate in the 1-2 kHz range in order to overcome the low frequency spectral noise. We have denominated this MEMS-based scheme Integrated Heterodyne Optical System (IHOS). The modulation efficiency of the proposed architecture can reach up to 50 percent. In order to implement the MOEMS optical modulators, a new two-mask fabrication process was developed that combines high-aspect ratio and low aspect ratio structures at the same device layer (aspect ratio is defined as a ratio between the structure height to its width). Long stroke electrostatic combdrive actuators integrated with folded flexures (high aspect-ratio) were fabricated together to drive large aperture shutters (low aspect ratio). We have denominated this process MASIS (Multiple Aspect Ratio Structural Integration). Under resonant excitation at approximately 1 kHz, MOEMS modulators demonstrated maximum displacement of about 40 microns at an actuation voltage of 15 V peak in air, and 3.5 V peak in vacuum (8 mTorr). Results of analytical solutions and finite element analysis (FEA) simulations are in good agreement with experimental data. A comprehensive model was developed that demonstrates the effective use of IHOS as a SNR enhancer of photodiode sensitivity, providing a 30 dB improvement in the detection limit. This work represents the first attempt for signal enhancement utilizing MEMS technology for detection of low intensity optical signals, and particularly for low intensity optical bio-reporter signals of whole-cell sensors. Whole-cell sensors are genetically modified cells that can be engineered to act as chemical-optical transducers. As the cells are exposed to toxins, photo-emission (bioluminescence) is triggered, providing optical emission levels per cell proportional to the toxicity concentration in the environment. The most important application that we are currently investigating is the implementation of whole-cell sensors as an early detection method against bio-terrorism. Bioluminescence detection becomes a very challenging task, as the maximum photo-emission rate per cell is limited to 300 photons/sec. The main intended application of the IHOS is to utilize it as a seamless add-on that will be placed in between photodiodes and whole-cell sensors, all of which combined into an inexpensive and portable toxicity reader. We believe that the ramifications of this new MEMS-based scheme can be also applicable to a vast number of applications for optical systems in which the SNR needs to be improved.

Electronically Directed Integration of Whole-Cell Biosensors on Bio-Chips

Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel This paper presents a whole-cell bio-chip system where viable, functioning cells are deposited onto solid surfaces that are a part of a micro-machined system. The development of such novel hybrid functional sensors depends on the cell deposition methods; in this work new approach integrating live bacterial cells on a bio-chip using electrophoretic deposition is presented. The bio-material deposition technique was characterized under various driving potential and chamber configurations. The deposited bio-mass included genetically engineered bacterial cells generating electrochemically active byproduct upon exposure to toxic materials in the aqueous solution. In this paper we present the deposition apparatus and methods, as well as the characterization results, e.g. signal vs. time and induction factor, of such chips and discussing the highlight and problems of the new deposition method.