Collaborators

• A. Amon, MIT
• T. Burg, MPI
• J. Foster, IMT
• A. Grossman, MIT
• S. Jiang, Univ of Washington
• M. Kirschner, Harvard
• P. Mallick, USC
• D. Sabatini, MIT

Postdoctoral Associates

• W. Grover, BE
• S. Knudsen, BE
• S. Olcum, BE
• S. Byun, BE

Graduate students

• A. Bryan, BE
• N. Cermak, CSB
• N. Chou, BE
• F. Delgado, BE
• A. Gulati, BE
• V. Hecht, BE
• J. Shaw, BE
• S. Son, ME
• M. Stevents, Biology
• Y.C. Weng, BE

Research Staff

• K. Payer, Research Specialist

Support Staff

• M. Murray

Publications

J. Lee, R. Chunara, W. Shen, K. Payer, K. Babcock, T. Burg, S.R. Manalis. Suspended microchannel resonators with piezoresistive sensors. Lab on a Chip 2011; 11 645-651.

J. Lee, W. Shen, K. Payer, T. Burg, S.R. Manalis. Toward attogram mass measurements in solution with suspended nanochannel resonators. Nano Letters 2010; 10 2537-2542.

M. Godin, F.F. Delgado, S. Son, W.H. Grover, A.K. Bryan, A. Tzur, P. Jorgensen, K. Payer, A.D. Grossman, M.W. Kirschner and S.R. Manalis. Using buoyant mass to measure the growth of single cells. Nature Methods 2010; 7 387-391.

J.E. Sader, T.P. Burg, S.R. Manalis. Energy dissipation in microfluidic beam resonators. Journal of Fluid Mechanics 2010; 650 215-250.

M.G. von Muhlen, N.D. Brault, S.M. Knudsen, S. Jiang, S.R. Manalis. Label-Free Biomarker Sensing in Undiluted Serum with Suspended Microchannel Resonators, Analytical Chemistry 2010; 82 1905-1910.

A. K. Bryan, A. Goranov, A. Amon, S. R. Manalis. Measurement of mass, density, and volume of yeast through the cell cycle. PNAS 2010; 107 (3) 999-1004.

P. Dextras, T.P. Burg, S.R. Manalis. Integrated Measurement of the Mass and Surface Charge of Discrete Microparticles Using a Suspended Microchannel Resonator. Analytical Chemistry. 2009; 81(11), 4517-4523.

T.P. Burg, J.E. Sader, S.R. Manalis. Non-Monotonic Energy Dissipation in Microfluidic Resonators. Physical Review Letters. 2009; 102 (22), 228103.

S.M. Knudsen, M.G. von Muhlen, D.B. Schauer, S.R. Manalis. Determination of Bacterial Antibiotic Resistance Based on Osmotic Shock Response. Analytical Chemistry 2009; 81(16), 7087-7090.

S. Son, W.H. Grover, T.P. Burg, S.R. Manalis. Suspended microchannel resonators for ultra-low volume universal detection. Analytical Chemistry. 2008; 80 4757-4760.

W.H. Grover, M. von Muhlen, S.R. Manalis. Teflon films for chemically-inert microfluidic valves and pumps. Lab on a Chip. 2008; 8 913-918.

T.M. Squires, R.J. Messinger, S.R. Manalis. Making it stick: convection, reaction, and diffusion in surface based biosensors. Nature Biotechnology. 2008; 26 417-426.

R. Chunara, M. Godin, S. M. Knudsen, S.R. Manalis. Mass-based readout for agglutination assays. Applied Physics Letters. 2007; 91 193902.

M. Godin, A.K. Bryan, T. Burg, and S.R. Manalis, Measuring the mass, density and size of particles and cells using a suspended microchannel resonator. Applied Physics Letters. 2007; 91 123121.

T.P. Burg M.Godin, W. Shen, G. Carlson, J.S. Foster, K. Babcock, and S.R. Manalis. Weighing of Biomolecules, Single Cells, and Single Nanoparticles in Fluid. Nature 2007; 446 1066-1069.

J. Hou, M. Godin, K. Payer, R. Chakrabarti, S.R. Manalis. Integrated Microelectronic Device for Label-free Nucleic Acid Amplification and Detection. Lab on a Chip 2007;  7 347-354.

Precision frequency detection has enabled the suspended microchannel resonator (SMR) to weigh single living cells, single nanoparticles, and adsorbed protein layers in fluid. To date, the SMR resonance frequency has been determined optically, which requires the use of an external laser and photodiode and cannot be easily arrayed for multiplexed measurements. Here we demonstrate the first electronic detection of SMR resonance frequency by fabricating piezoresistive sensors using ion implantation into single crystal silicon resonators ^[1] . To validate the piezoresistive SMR, buoyant mass histograms of budding yeast cells and a mixture of 1.6-, 2.0-, 2.5-, and 3.0-mm-diameter polystyrene beads are measured. Figure 1 shows our experimental setup. For piezoresistive detection, a Wheatstone bridge is built with the piezoresistor and three external resistors. The bias voltage (5 V) is selected to maximize the signal while limiting the temperature increase in the piezoresistor due to resistive heating. Figure 6 shows mass resolution derived from mass sensitivity and Allan variance.  In summary, the mass resolution achieved with piezoresistive detection is comparable to what can be achieved by the conventional optical-lever detector in 1 kHz bandwidth. Eliminating the need for expensive and delicate optical components will enable new uses for the SMR in both multiplexed and field deployable applications.

1. J. Lee, R. Chunara, W. Shen, K. Payer, K. Babcock, T. Burg, and S. R. Manalis, “Suspended microchannel resonators with piezoresistive sensors,” Lab on a Chip, vol. 11, no. 4, pp. 645-651, Feb. 2011.

Using suspended nanochannel resonators (SNRs), we demonstrate measurements of mass in solution with a resolution of 27 ag in a 1-kHz bandwidth, which represents a 100-fold improvement over existing suspended microchannel resonators and, to our knowledge, is the most precise mass measurement in liquid today ^[1] . As shown in Figure 1a,b, SNR consists of a cantilever that is 50 µm long, 10 µm wide, and 1.3 µm thick, with an embedded nanochannel that is 2 µm wide and 700 nm tall. The SNR has a resonance frequency near 630 kHz and exhibits a quality factor of approximately 8000 when dry and when filled with water. Figure 2 shows mass histograms corresponding to short- term (10 s, 1 kHz bandwidth) baseline frequency noise and the frequency shift measured from a population of 50-nm diameter gold nanoparticles in the flow-through mode, also at a 1-kHz bandwidth. The standard deviation of the baseline frequency noise is 38.6 ppb, and the mass sensitivity of 0.890 Hz/fg is deduced from the size specification of the nanoparticles and the density of gold. The average and standard deviation of the measured gold nanoparticles are 1.20 and 0.20 fg, respectively.  In addition, we introduce a new method that uses centrifugal force caused by vibration of the cantilever to trap particles at the free end. This approach eliminates the intrinsic position- dependent error of the SNR and also improves the mass resolution by increasing the averaging time for each particle.

1. J. Lee, W. Shen, K. Payer, T. Burg, and S. R. Manalis, “Toward attogram mass measurements in solution with suspended nanochannel resonators,” Nano Letters, vol. 10, no. 7, pp. 2537-2542, July 2010.