DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-12 in the reply filed on December 29, 2025 is acknowledged.
Claims 13-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 29, 2025.
Information Disclosure Statement
The two IDS received on July 11, 2023; IDS received on November 7, 2025 and September 23, 2025 are acceptable and are being considered by the Examiner.
Drawings
The drawings received on March 1, 2023 are acceptable.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite because the phrase, “the top electrode immersed in buffer” in step (d) and the phrase, “the buffer is deposited sufficiently so as to conduct a current that may be detected …” render the limitation unclear in whether the claimed product comprise the buffer resulting in the top electrode being immersed therein, or the buffer is an intended step limitation (connoted by “is deposited sufficiently”) which is not actively present in the claimed product.
Claim 5 recites the phrase, “the PNA capture probe”. It is unclear which of the “one or more charge-neutral peptide nucleic acid (PNA) capture probes”, the PNA capture probe is referring to.
Claim 8 recites the phrase, “the foil electrode” in element (c)(2). There is an insufficient antecedent basis for this limitation in the claim. For the purpose of prosecution, the phrase has been construed to refer to “the electrode” of element (a)(4).
Claims 2-7 are indefinite by way of their dependency on claim 1.
Claims 9 and 10 are indefinite by way of their dependency on claim 8.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-6, 8-10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Koo et al. (Lab on a Chip, July 2018, vol. 18, no. 15, pages 2291-2299) in view of Lafleur et al. (Lab on a Chip, 2016, vol. 16, pages 3777-3787).
With regard to claim 1, Koo et al. teach an apparatus for detecting specific nucleic acids (“we sought to detect specific 16S rRNA sequences”, page 2292, 2nd column, 3rd paragraph) comprising:
a pore in contact with a top side of a membrane (“we have developed the means to fabricate thin glass membranes in which a nanopore may be milled with a focused ion beam (FIB)”, page 2292, 2nd column, 3rd paragraph, see also “nanopore was milled at the center of the etched membrane …”, page 2293, 1st column, bottom paragraph; also Fig. 1a);
a bottom electrode disposed on the bottom side of the membrane;
a top electrode disposed above the pore, the top electrode immersed in buffer (Ag/AgCl pellete electrode was placed in each of the chambers on either side of the pore … electrodes were connected to a multichannel potentiostat (VMP3) interfaced to a computer running EC-Lab software for data collection”, page 2295, 1st column; also “[t]est buffer (200 mL) was pipetted into each chamber to ensure that the pore connecting the two chambers were filled with buffer”, page 2294, 2nd column);
wherein the buffer is deposited sufficiently so as to conduct a current that may be detected between the top electrode and the bottom electrode; and
wherein the current passes through the pore upon application of a voltage between the top electrode and the bottom electrode (“the current was monitored for sustained ionic current drops at 1.5 V that would signal detection of target 16S rRNA … a current drop was seen due to pore blockage, the potential was held for at least one minute to ensure that the block was not simply a transient caused by PNA-bead conjugates weakly bound to non-target RNA”, page 2295, 1st column, 1st paragraph).
With regard to claim 2, the pore is a substantially cylindrical shape with a smallest diameter of about 500 nm (see Fig. 1(c); “larger diameter end on the etched side of the glass chip and the smaller opening on the smooth backside”, page 2293, 2nd column, 1st paragraph).
With regard to claim 3, the pore substantially comprises borosilicate glass (“[f]our inch-diameter glass borosilicate wafers (200 mm thick) were first patterned …”, page 2293, 1st column, 3rd paragraph; also “[g]lass chips with submicron-thick membrane and a single nanopore were microfabricated”, page 2297, 2nd column, 3rd paragraph).
With regard to claim 4, the above (i.e., glass chip assembly) etched portion of the borosilicate glass is less than or equal to about 1 mm in thickness (see above), wherein the pore is disposed within the etched portion (see above); and a PDMS top pattern deposited over the borosilicate glass comprises a circular opening centered over the pore and the side opposite from the pore (“glass chip containing a single nanopore was sandwiched between two Teflon chambers … using polydimethylsiloxane (PDMS) o-rings as seals”, page 2295, 2nd column, bottom paragraph).
With regard to claim 5, one or more charge-neutral peptide nucleic acid PNA) capture probes conjugated to polystyrene beads, said PNA-capture probe is designed to capture a target pathogenic DNA/RNA is comprised therein (“[p]olystyrene microbeads …”, page 2292, 2nd column, bottom paragraph; “[b]eads with conjugated PNA probes … RNA samples were hybridized with beads conjugated to PNA selective for E. coli (E. coli PNA-beads)”, 2nd column, 3rd paragraph; see also, “[b]eads … were injected in the chamber on the smooth backside of the chip where the tapered pore opening is smallest …”, page 2295, 1st column, 1st paragraph).
With regard to claim 6, the diameter of the pore is less than the diameter of the polystyrene beads (“[p]olystyrene microbeads of 820 nm diameter …”, page 2292, 2nd column, bottom paragraph; also, the beads block the pore “[b]eads … were injected … After a current drop was seen due to pore blockage”, page 2295, 1ST column, 1st paragraph).
With regard to claim 9, the glass chip assembly comprises a pore wherein droplet of hybridization buffer is disposed in the circular opening of the PDMS top pattern of the glass chip assembly (“[t]est buffer (200 mL) was pipetted into each chamber to ensure that the pore connecting the two chambers was filled with buffer”, page 2294, 2nd column, bottom paragraph), wherein the Ag/AgCl electrode is immersed at one end of the droplet (see above).
With regard to claim 10, the device of Koo et al. also comprises a potentiostat for measuring current that passes through the nanopore (“electrodes were connected to a multichannel potentiostat … current was monitored for sustained ionic current drops”, page 2295, 1st column).
Koo et al. provide a direct delivery of the PNA-bead/target nucleic acid complex to the pore of the glass chip assembly for detection and therefore, do not teach that a lateral flow membrane having a top side and a bottom side, a loading side and an absorbing side and that the pore of the glass chip is in contact with the top side of the lateral flow membrane (claim 1, in-part, claim 8, and 12).
Lafleur et al. teach a lateral flow device which is configured to apply and deliver a target nucleic acid and probe complex to a downstream detection region, wherein the flow of the complex is produced by wicking region at the opposite end (see Fig. 3, below):
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As seen, the device is employed to receive a sample at the loading area, reagent complexing area (i.e., amplification & detection dry reagent pad), a downstream detection area (detection region), and opposite end “waste pad” which is synonymous to absorbing side (allowing sample to migrate by wicking).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Koo et al. with the teachings of Lafleur et al., thereby arriving at the invention as claimed for the following reasons.
The teaching of Koo et al. is directed to a method of detecting the presence of a target nucleic acid based on it binding to a charge neural PNA probe which is immobilized to a bead having a diameter greater than that of a pore (nanopore) which is configured on a glass substrate membrane. A positive detection is made when a potentiostat is employed to generate a potential difference, wherein target nucleic acid bound PNA-bead is rendered charge negative, and migrate toward the pore. However, due to the size of the pore, the target nucleic acid bound PNA-bead complex become stationary at the pore and remains at the pore at a current longer than those that are not bound to the PNA-bead complex (i.e., non-specific target nucleic acids which will simply migrate through), non-specific target nucleic acids which are transiently bound to the PNA-bead complex which will not stay bound to the PNA at the current for the observed duration, or non-target bound PNA which remains charge neutral.
And while Koo et al. provided the target nucleic acid and the PNA-bead probes directly on the chambers which flank the nanopore of the glass chip assembly, one of ordinary skill in the art would have been motivated to combine the teachings of prior art which would have allowed the process of sample application to detection in a standalone device which is portable, such as lateral flow strip sample/reagent delivery.
Indeed, Lafleur et al. teach:
“The ideal diagnostic would improve sensitivity, but mimic the simplicity, of the most LRS [low resource setting] platform … Our research is aimed at developing non-instrumented, point-of-care NAAT systems for LRS applications …” (page 3778, 1st paragraph)
In addition, since Lafleur et al. teach that a lateral flow test membrane can be utilized to receive a sample comprising nucleic acid, mix the necessary labeling reagents, and flow the resulting complex to a downstream detection region, one of ordinary skill in the art would have had a reasonable expectation of success at utilizing same flow means to receive and mix the detection reagents of Koo et al. (i.e., target RNA and PNA-beads) and flow them to a downstream detection region comprising the glass chip assembly which is configured to receive the detection complex therein.
Lastly, it is determined that substituting the detection means of Lafleur et al. with the detection means of Koo et al. to receive the detectable complex at a downstream glass chip assembly would not have been beyond that skill level of the ordinarily skilled artisan since Lafleur et al. demonstrated that test sample can be received, combined with detectable reagents, as well as perform an elaborate reaction (amplification reaction) prior to the detection.
In KSR International Co v. Teleflex Inc, the supreme court stated that, “A person of ordinary skill in the art is also a person of ordinary creativity, not an automation” (82 USPQ2d at 1397) and that “in many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle” and take into account, “the inference and creative steps that a person of ordinary skill in the art would employ” (82 USPQ2d at 1396).
“When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, 103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill.” (page 13, emphasis added, KSR).
Therefore, for these reasons the invention as claimed is deemed prima facie obvious over the cited references.
Conclusion
Claims 1-10 and 12 are rejected. Claim 11 is allowable.
Claims 7 and 11 are free of prior art.
Claim 7 recites that the apparatus further comprises a magnet adjacent to a deposition point of the polystyrene beads and that the polystyrene beads comprise magnetite in part. Claim 11 recites that the apparatus comprises a magnetic bead-PNA conjugate.
While magnetic beads have been known in the art to be conjugated to nucleic acid molecules, there is no legal motivation to utilize them into the device of Koo et al. This is because the PNA-beads travel to the downstream detection region by sample migration via lateral flow means.
The usage of magnetic bead-PNA conjugates is employed in the present invention in order to place and hold the reagents in proximity
“In one embodiment, the technology described in this disclosure comprises the integration of a glass chip harboring a thin glass membrane and pore with a lateral flow membrane and the use of magnetic polystyrene bead-PNA (peptide nucleic acid) conjugates to control bead location on the membrane and to position the beads in proximity to the glass chip for detection of bead-PNA conjugates with hybridized target nucleic acid. It should be noted that although magnetic polystyrene bead-PNA has been used in this embodiment, other magnetic substrates able to be conjugated with charge-neural peptide nucleic acid (PNA) capture probes could also be used, including other charge neutral nucleic acid analogs (section [0025])
“the lateral flow nucleic acid assay with integrated pore-based detector 300, a magnet 322 is used to maintain a position of polystyrene beads comprising magnetite, thereby having ferromagnetic materials may be used to render the polystyrene beads ferromagnetic. The magnet 322, which can be a neodymium magnet, another permanent magnet, or an electromagnet, is used to hold the magnetic PNA-beads in place while sample is drawn over the beads to effect hybridization (section [0076])
There simply would have been no reason to utilize a magnetic bead in the PNA-bead complex.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YOUNG J KIM/Primary Examiner
Art Unit 1637 January 21, 2026
/YJK/
There is strong impetus for the conception and development of low-cost, accurate, and robust point-of-care (POC) nucleic acid (NA) -based diagnostic devices that give results in minutes. (section [0007])
Generally, optical methods are used for amplicon detection, which necessitates the incorporation of optical components into the instrument with associated increased complexity and cost. Despite impressive advances in rapid methods for polymerase chain replication (PCR) cycling, the need for precise temperature control has driven many test developers to pursue isothermal amplification methods, but these methods still require primers, polymerases as well as reaction conditions that must be carefully controlled (section [0014])
Broadly applicable, NA amplification-free, label-free, sequence-specific NA detection schemes are rare. Over the past 10 years or so, remarkable progress has been made in developing new approaches for amplification-free NA detection at clinically relevant concentrations in the single-digit attomolar (aM, 10-18M) range and below. However, only a handful of these schemes do not require special labels other than an oligonucleotide complementary to the target NA. Also, nearly half require optics of some kind. The remaining approaches entail piezoelectrics, MALDI TOF MS … or various electrochemical techniques (section [0015])
The RNA/DNA detection disclosed here is distinct from other nanopore-based NA sensing systems in that it is not a resistive-pulse sensor based on the work of Coulter … where the conductance of an electrolyte-filled pore or channel is monitored as various analyte species traverse it. Rather it is based on far simpler conductometric detection of large signals from long-lasting pore blockages (section [0018])
“The resistive-pulse approach is focused on precise measurement of small changes in nanopore current over short timescales (us ot ms) as analytes traverse a pore, whereas the device technology disclosed here intrinsically amplifies this signal into the nA-range and extends its duration indefinitely by relying on persistent pore blockages to signal the presence of analyte (section [0019])
This approach greatly simplifies device electronics and readout, as described in … WO 2013/033647 A2, published on March 7, 2013 and incorporated herein by reference in its entirety (section [0020])
Nonspecifically bound NA rarely gives a persistent signal. Note that a ‘signal’ is a persistent step reduction in ionic current that lasts several seconds or longer. Most control runs with non-complementary NA lead to no observable pore blockades; only some transient blockades (not lasting long enough to constitute a signal) are observed infrequently. Yet, it has been observed that incubation of the beads with non-complementary NA occasionally results in substantial nonspecific binding as noted by an increase in zeta potential from the single digit range to about 20 to about 30 mV. Thus, these beads with nonspecifically bound DNA are negatively charged and electrophoretically mobile, allowing them to be driven to the pore. (section [0021])
At the pore mouth, the electric field is sufficiently strong to remove the nonspecifically bound DNA from the bead, which causes a reduction in bead charge and electrophoretic mobility, enabling the opposing drag due to electroosmostic flow to exceed the electrophoretic force and carry the bead away from the pore. This electroosmotic flow arises from an opposing flux of positive counterions to fixed negative charges on the glass pore wall (section [0023]
Experimental evidence, as well as results of many control studies show that beads with only nonspecifically bound NA approach a pore mouth briefly and then are propelled away by the opposing electroosmotic flow despite possible mobility due to dielectrophoresis. The literature does not appear to disclose another NA-based diagnostic system with such an active system to avert false positives (section [0023])
In one embodiment, the technology described in this disclosure comprises the integration of a glass chip harboring a thin glass membrane and pore with a lateral flow membrane and the use of magnetic polystyrene bead-PNA (peptide nucleic acid) conjugates to control bead location on the membrane and to position the beads in proximity to the glass chip for detection of bead-PNA conjugates with hybridized target nucleic acid. It should be noted that although magnetic polystyrene bead-PNA has been used in this embodiment, other magnetic substrates able to be conjugated with charge-neural peptide nucleic acid (PNA) capture probes could also be used, including other charge neutral nucleic acid analogs (section [0025])
An important feature of the detector is the use of peptide nucleic acid (PNA) capture probes, which are unchanged polyamide analogs to DNA that share the same base chemistry. Since bead-PNA conjugates are designed to be charge neutral, they do not exhibit appreciable electrophoretic movement in the presence of a DC electric field. However, the substantial negative charge acquired upon capture of a target NA sequence makes the hybridized conjugate mobile” (section [0027])
Electrophoresis of the bead-PNA conjugate with hybridized target NA to the mouth of a smaller diameter glass pore causes a significant increase in pore resistance, thereby resulting in a persistent strong, sustained drop in measured ionic current. Nonspecifically bound NA is removed from the bead conjugate in the strong electric field in the pore mouth resulting in no sustained signal. Further the opposing electroosmotic flow through the glass pore sweeps PNA-based conjugates without hybridized target away from the pore mouth. In such a way, this simple conductometric device gives a highly selective (rarely observed false positives), binary response signaling the presence or absence of the target NA (and associated pathogen). (section [0028])
“polystyrene bead 116 has hybridized to three instances of the single-stranded nucleic acid targets (DNA or RNA 112). This bonding has created a net of many negative charges on the bonded polystyrene bead 116 corresponding to the length of the target, thereby enabling it to become electrophoretically motile (or electromotile) due to imposed electric field between the applied positive voltage V+ 104 and a negative voltage V-106 (section [0053])
Normally, the charged single-stranded nucleic acid targets (DNA or RNA, 112) proceed 122 without interruption through the pore 114 in the membrane 102 since the pore 114 is much larger. Therefore, the charged single-stranded nucleic acid targets (DNA or RNA, 122) pass through the much larger pore 114 without causing an appreciable disruption in the ionic current through the pore 114 (section [0054])
PNA is an uncharged nucleic acid analog. Any remaining carboxyl groups are capped first with amine-terminated polyethylene glycol (PEG) and then with ethanolamine. It is important that PNA be conjugated on the beads at an optimal surface density. Remaining carboxyl groups on the bead surface must be capped. Here, polyethylene glycol (PEG) is used to help prevent bead aggregation. Ethanolamine is used to cap any remaining carboxyl groups and is necessary to achieve near electroneutrality. After these bead modification steps, the beads have low single-digit, negative mV zeta potential (and are essentially neutral) and are not appreciably mobile in a moderate electric field (section [0056])
However, RNA and DNA 112 carry substantial negative charges, and when target RNA or DNA hybridizes to 120 to the PNA on the modified beads, as shown on the bonded polystyrene bead 116, the complex carries sufficient negative charge to be mobile in the imposed electric field (V-106 to V+104). (section [0057])
When the PNA-beads with hybridized target, resulting in the bonded polystyrene bead 116, approaches the pore 114 opening, an appreciable, sustained deflection of ionic current occurs. This sustained reduction in ionic current is termed ‘persistent’ (section [0058])
“lateral flow nucleic acid assay with integrated pore-based detection. A glass substrate, such as a borosilicate glass microscope slide, is used as a substrate 302. Upon the glass substrate 302 is placed a membrane 304, which has a bottom side 306 and a top side 308. On one lateral side of the membrane 304 is a sample leading area 310 (section [0065])
A glass chip 312 comprises a fabricated micro- or nano-pore 114 as previously described above FIG. 1. This pore 114 is difficult to view in this drawing, since it is about 500 nm in diameter. The glass chip 312 is attached to the membrane 304 on the top side 308, and conductively coupled to a platinum electrode 314 on the other side through the use of a conductive buffer 316 droplet (section [0066])
These glass chips 312 will be incorporated into single-use assay cartridges containing the PNA-beads and the process fluidics. (section [0067)
Between the membrane 304 and bottom side 306, and the substrate 302 is also emplaced a platinum foil electrode 318 to which a conductive wire 320 is attached. The platinum foil electrode 318 and the platinum electrode 314 are situated in such a way as to conduct a sensible current through the glass chip 312 as ions pass through the pore 114 (section [0068]).
In operation, a sample is loaded onto the sample loading area 310, where the membrane 304 transports the sample laterally across the glass chip 312 via capillary action of the membrane 304, and more importantly, in proximity to the pore 114. Such capillary based membranes 304 may be nitrocellulose-based, glass fiber-based, or other material essentially nonreactive to the materials used in practicing this invention (section [0070])
Such a membrane 304 has a large enough effective pore size such that either magnetic or non-magnetic PNA-beads can move through it. With the Fusion 5 membrane 304, a separate sample loading area 310 (composed of a different material) would be unnecessary, but a separate sample pad could be used. If larger liquid samples are used, an additional absorption pad may be added downstream of the glass detector to absorb excess liquid, thereby facilitating flow along the lateral flow membrane (section [0071])
“the lateral flow nucleic acid assay with integrated pore-based detector 300, a magnet 322 is used to maintain a position of polystyrene beads comprising magnetite, thereby having ferromagnetic materials may be used to render the polystyrene beads ferromagnetic. The magnet 322, which can be a neodymium magnet, another permanent magnet, or an electromagnet, is used to hold the magnetic PNA-beads in place while sample is drawn over the beads to effect hybridization (section [0076])
a top pattern 324 of … PDMS is seen. This pattern is deposited on a top surface of the glass chip 312 so as to better keep the conductive buffer 316 droplet from spreading away from the platinum electrode 314. This is better accomplished via the circular opening 326 situated over the pore 114 (section 0077)
The target nucleic acid hybridizes to the PNA-beads when a sample is introduced at the sample loading area 310, flows over them. Next, the magnet 322 is removed so that the beads with hybridized target can move toward the glass chip and block pore 114. Typically, the sample is moved by capillary action of the membrane 304 by addition of a chaser fluid, that acts to ‘flush’ the target toward the pore 114 (section [0078])
“sample (e.g., urine, blood) will be drawn into the syringe, lysis (i.e., chemical disruption of microbial cell envelopes or disruption of viral capsid) will occur in about a minute. Subsequently several drops of lysed sample will be deposited onto the sample pad area of the assay device through a submicron filter (0.1 um pore size) attached on the syringe. The filter is likely necessary to remove particulate matter that, if negatively charged, could cause pore blockage and result in a false positive signal (section [0081])
PNA-beads are deposited previously on the membrane 304 in a position very near to the glass chip 312 detector or directly beneath it. The glass chip 312 may be deposited on the membrane 304 by any means that enable it to be attached in a state where the glass membrane 304 is wetted without any trapped air bubbles on either side (section [0082])
“Filtered sample … is added to one end of the Fusion 5 membrane (in the sample loading area), followed by sufficient buffer (10 mM NaCl, 25 mM Tris-HCl, pH 7.0) to chase the sample down the membrane strip and over the PNA beads (section [0095])
A droplet of buffer is placed on an inverted chip. The chip is then quickly flipped and positioned on the Fusion 5 membrane directly above the PNA beads, magnet and foil electrode. Next a drop of buffer is added to a reservoir on the top side of the chip to cover the glass membrane and an electrode is placed in this reservoir (section [0097])