Session U36: Nanoinstrumentation for Biological and Other Applications

Cocaine detection using piezoresistive microcantilevers

Sensitive and inexpensive sensors play a significant role in the analysis of drugs and drug metabolites. Specifically, reliable \textit{in vivo} detection of cocaine and cocaine metabolites serves as a useful tool in research of the body's reaction to the drug and in the treatment of the drug addiction. We present here a promising cocaine biosensor to be used in the human body. The sensor's active element consists of piezoresistive microcantilevers coated with an oligonucleotide-based aptamer as the cocaine binder. \textit{In vitro} cocaine detection was carried out by flowing a cocaine solution over the microcantilevers. Advantages of this device are its low power consumption, its high sensitivity, and its potential for miniaturization into an implantable capsule. The limit of detection for cocaine in distilled water was found to be 1 ng/ml.   

Bioinspired optical sensing of picomolar concentrations of lead in solution.

Lead poisoning is a life threatening medical condition, which can cause irreversible neurological, cardiovascular and reproductive damage. Despite of an extensive research, the minimum amount of lead to be considered hazardous is not yet known. The biophysical interactions of minute quantities of lead with blood are also poorly understood. Albumin being the most important binder and transporter in blood, is known to interact with lead ions in solution. In this report, we present the first experimental evidence that picomolar concentrations of lead strongly affect albumin properties in solution. High precision difference Raman and excitation-emission fluorescence spectroscopies are employed to identify the effect of lead ions on albumin. Both spectroscopies proved to be very effective in detecting lead poisoning at a very early stage, setting a new course for bio-inspired inexpensive platform of lead sensing   

Nanofluidic redox-cycling in electrochemical biosensing applications

We have developed a chip-based nanofluidic device which amplifies the sensitivity in electrochemical biosensing applications by orders of magnitude. The amplification is based on rapid redox-cycling between plane parallel electrodes inside a nanochannel. We show that it is possible to monitor the signal of less than a hundred molecules residing in the active area of the nanofluidic sensor. The small number of molecules is reflected in the noise spectrum of the device. In particular, we obtain high sensitivities when detecting catecholamines, which comprise an important group of hormones and neurotransmitters such as serotonin and dopamine. Furthermore, due to the nanochannel design, the sensor is immune to interference by molecules undergoing irreversible redox reactions. We demonstrate the selectivity of the device by detecting target molecules in the presence of ascorbic acid whose oxidized form is only stable on the order of milliseconds. The interference of ascorbic acid is usually a challenge in the detection of catecholamines in biological samples.   

Detection of Target Biomolecules by Magnetic Reporting Using Rod-Like Nanosensors

We describe the ongoing development of a device to assay a variety of cellular, viral and molecular targets by measuring the increase of the Brownian relaxation time, $\tau $, in solution of magnetically-tagged nanoscale detectors. The shift shows as a frequency reduction of the peak of the complex magnetic susceptibility, $\chi (\omega )$''. Measurements of $\chi (\omega )$'' with 12 nm monodisperse nanoparticles of CoFe$_{2}$O$_{4}$ coated with polyethelyne glycol reveal spectra with the narrowest lines yet reported. Thin avidin coating of these particles reveals small shifts in $\chi (\omega )$''. Bacteriophage T4 tail fibers, engineered to specific lengths (30-150 nm), were employed as the platform for magnetic nanoparticle attachment and at the other end for an inserted target peptide epitope. Attachment of the nanoparticles to bacteriophage T4 tail fibers was successful, though no detectable shifts in $\chi (\omega )$'' were detected due to weak attachment. The advantages associated with non-spherical geometry detectors will be discussed, as will preliminary measurements with rare earth oxide magnetic nanoparticles. Progress on miniaturization and low power requirements of the electronic detection system will be reported. Supported by NERCE/BEID (NIAID).   

A Ringdown Breath Analyzer for Diabetes Monitoring: Breath Acetone in Diabetic Patients.

It is highly desirable for millions of diabetic patients to have a non-blood, non-invasive, point-of-care device for monitoring daily blood glucose (BG) levels and the adequacy of diabetic treatment and control. Cavity ringdown spectroscopy, due to its unique capability of high sensitivity, fast-response, and relatively low cost for instrumentation, has the potential for medical application through non-invasive analysis of breath biomarkers. We report the first ringdown acetone breath analyzer for clinic testing with diabetic outpatients. The instrument was set in a clinic center and 34 outpatients (24 T1D and 10 T2D) were tested during a four-day period. 10 T1D subjects and 15 nondiabetic persons were tested in our laboratory. Three juvenile-onset T1D subjects were selected for a 24-hr monitoring on the variations of breath acetone and simultaneous BG level. In this talk, we present our research findings including the correlations of breath acetone with BG level and A1C.   

Integrating Different Types of Nanowire Sensors in a Large Array

Biological olfactory systems have a key structural feature: different types of sensors in a large array. Humans, for example, possess several hundred distinct types of sensing cells, a level of sensor diversity not yet achieved in artificial olfactory systems. Here, we demonstrate a simple and low-cost electrochemical approach to integrate large numbers of different types of nanowire sensors in an array on the same silicon wafer. In our approach, nanowires are grown inside an on-chip nanochannel template by electrochemistry with each horizontal channel connected to a gold electrode. This design allows for addressable synthesis of a specific type of nanowire in specified channels by providing a voltage to the electrodes connecting to those channels. The process can be further repeated to produce different types of nanowires in other channels using different electroplating solutions. The scale and diversity of this array have a potential to compete with those of biological olfactory systems and the synthesis process is cost-effective enough for commercialization.   

Compact Femtosecond-Millisecond Transient Absorption Spectrometer

The measurement of population dynamics in biological, chemical, and solid-state samples occurring over 10$^{-15}$-10$^{1}$ seconds requires a combination of transient absorption techniques, typically involving different laser systems and detection electronics (e.g. femtosecond transient absorption and nanosecond flash photolysis). The difficulty in exactly matching excitation conditions often prohibits connecting ultrafast and longer time measurements, particularly in samples exhibiting nonlinear kinetics. We present a simple solution to bridge the femtosecond and microsecond domains with an inexpensive modification of a kHz amplified Ti:Sapphire laser. By introducing a secondary pulse-picker between the laser oscillator (75 MHz) and amplifier, we can electronically delay unamplified 800-nm probe pulses in 13.3-ns steps. The 5-nJ pulses seed a photonic crystal fiber to produce a supercontinuum (450-1100 nm) for broadband probing. We demonstrate the system capability by resolving formation and decay dynamics, spanning 10 decades (10$^{-14}$-10$^{-4}$ s), of photoexcited solvated electrons in sinapic acid, and triplet states and quinonoid intermediates in Vitamin B$_{6}$.   

Realization of Confocal and Hyperspectral Microscopy via Compressive Sensing

Given its important role, factors such as sensitivity, resolution, dwell time, and bandwidth limit are critical parameters for detectors in modern microscopy. A new method known as compressive sensing has emerged, which greatly improves the imaging resolution of these detectors. In our configuration, a digital micromirror device randomly but controllably modulates the light before it is collected at the detector. This process simultaneously compresses the signal because the measurement projects the signal onto a white-noise basis. Subsequently, the data from this incoherent basis is reconstructed into a complete real-space image. Given its compressive nature, far fewer measurements are required than the total number of pixels which greatly decreases the acquisition time of the signal. In addition, the intensity of the compressed signal at the detector is much greater than its raster scan counterpart and therefore results in greater signal sensitivity and improved image quality. These advantages make compressive sensing particularly attractive for use in hyperspectral and confocal microscopy.   

Fabrication of robust superconducting granular aluminum/palladium bilayer microbolometers with sub-nanosecond response

We provide a convenient recipe for fabricating reliable superconducting microbolometers as acoustic phonon detectors with sub-nanosecond response, using image-reversal optical lithography and dc-magnetron sputtering, and our recipe requires no chemical or plasma etching. Our approach solves the traditional problem for granular aluminum bolometers of unreliable (i.e., non-Ohmic) electrical contacts by sequentially sputtering the granular aluminum film and then a palladium capping layer. We use dc calibration data, the method of Danilchenko et al., and direct nanosecond-pulsed photoexcitation to obtain the microbolometer's characteristic current, thermal conductance, characteristic relaxation time, and heat capacity. We also demonstrate the use of the deconvolution algorithm of Edwards et al., to obtain the phonon flux in a heat pulse experiment with nanosecond resolutio.   

Highly Sensitive Photodetector Based on a Self-assembled Organic Single Submicrometer Ribbon

We demonstrated a highly sensitive air-stable photodetector based on a single submicrometer organic crystalline ribbon self-assembled from a condensed benzothiophene via solution process. The low cost and simple solution process was employed in the device fabrication process from the submicrometer ribbons preparation to the deposition on the substrate. The photoconductivity gain is up to 1.3 $\times $ 10$^{3}$, while the responsivity is about 420 A/W at the field of 2 $\times $ 10$^{4}$ V/cm. The highest on/off ratio reaches around 1000. The performance is comparable to that of photodetectors based on inorganic nanowires, and even better than those based on carbon nanotube or other bilayer molecular self-assembled nanotubes. In addition, the photo-switching properties to those organic photodetectors were investigated with different metal electrodes. The results show that the surface states created by the thermal evaporation of the heavy gold atoms are responsible for the high photo gain and the slow photocurrent decay. To our best knowledge, this is the first report on photodetectors based on crystalline organic 1D submicrometer ribbons self-assembled via solution process, which combine both advantages of intrinsic properties of the 1D crystalline structure and the simplicity of the solution process.   

Single carbon nanotube syringe: A model for the study of liquid transport through individual carbon nanotubes

The hollow structure of the carbon nanotubes (CNT) and their ability to translocate through plasma membrane of a living cell provide a significant chance to use them as a nano syringe for the delivery of therapeutically active molecules into a live cell. However, the size and the extremely high aspect ratio of the CNTs make the nano syringe device difficult to realize. We successfully prepared a monolithic multiwall CNT with a graphitic shield by chemical vapor deposition technique. The graphitic shield provides a handle which allows the manipulation of the supported CNTs. A single CNT syringe device is fabricated with focused ion beam technique. The well-controlled liquid transport through individual CNT is demonstrated.