Coulter counter having a plurality of channels

#The present invention is generally related to a multichannel particle counting method and a device for practicing the method. Such counters can be used to count micro-scale and/or nano-scale particles and the like. Counters within the scope of the present invention generally operate by sensing changes in resistance, conductivity, conductance or the like. More particularly, as a particle passes through a channel, it disrupts the ion current therein, thus increasing the channel's resistance.

#Quantitative measurements of the size and concentration of micro and nano scale particles has been accomplished using Coulter counters. A typical Coulter counter device comprising a single micropore that separates two chambers containing electrolyte solutions. When a particle flows through the microchannel, it results in the electrical resistance change of the liquid filled microchannel. The resistance change can be recorded in terms of current or voltage pulses, which can be correlated to size, mobility, surface charge and concentration of the particles. Due to the simple construction of these devices and the reliable sensing method, Coulter devices have found application in a broad range of particle analyses from blood cells to polymeric beads, DNA, virus particles and even metal ions.

#One substantial disadvantage of existing Coulter counters is their low throughput efficiency, which substantially extends measurement times. Coulter counting measurement relies on particles passing through a tiny orifice (microchannel) one by one from one chamber to the other. Thus, in order to complete sampling of a small number of particle solutions, thousands of micro or nanoparticles have to pass through the orifice one by one, which could be prohibitively time consuming. For instance, one estimate shows that a sample having a particle concentration of 108 particles/mL (v/v ratio 0.026%) requires 27.7 hours to complete a measurement, assuming each particle takes about 0.05 seconds to pass through the orifice, only one particle is resident in the orifice at any given time, and assuming a 0.01 mL sample volume. The measurement time is further extended as the orifice size decreases.

#FIG. 1 is a schematic showing the a multichannel particle counting device;

#FIG. 2 is a diagram pictorially showing the resistance of each sensing element. Note that R and R′ (i.e., the resistances of the electrolytes outside the channel) can be neglected when compared to the channel resistances Rch and R′ch;

#FIG. 3 is an electrical schematic showing an example embodiment of the present invention comprising a 3-channel multiplexing particle counting device;

#The present invention generally relates to a method for rapidly counting particles using a plurality of orifices for simultaneously sensing particles. The present invention also generally relates to a device for practicing the method of the present invention.

#The method of the present invention includes providing a plurality of orifices that are capable of passing particles to be counted, wherein the diameter of the orifices is such that they can pass the particles one at a time, i.e., in single file. In general the orifices separate two electrolyte solutions, wherein one solution is in electrical communication with a cathode and the other is in electrical communication with an anode. When a voltage is applied across the cathode/anode pair, an ion current flows through the orifices. Thus, a signal is generated when at least one particle enters at least one orifice, thereby obstructing the flow of ion current and raising resistance. The signal can be read conveniently in terms of current or voltage. Furthermore, the present invention simultaneously detects particles in a plurality of orifices. Since these orifices are in a parallel electrical relationship, the signals generated thereby are multiplexed, and thus must be deconvoluted. The Hardmard transformation makes it possible to deconvolute the signal of the multiplexed particle counting device of the present invention.

#Membranes within the scope of the present invention can be fabricated from a wide variety of materials including without limitation organic polymers such as polymethyl methacrylates, polycarbonates, polyimides, polyphenols, chlorinated polyolefins, and the like. Additionally, membranes within the scope of the present invention can be fabricated from silicon, n-type silicon, p-type silicon, and the like. Membrane materials within the scope of the present invention should be stable under ordinary usage conditions, and should be capable of forming the pores and other micro and/or nano structures comprising the present invention.